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Biomedical subjects

J Philippe

Publications and source records attributed to J Philippe.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Repolarization anomalies in postoperative ECG after aorto-coronary bypass].

The authors studied 164 patients admitted in 1994 to their rehabilitation centre less than 5 weeks after a coronary artery bypass graft. They performed an ECG on admission and noted the presence and localization of repolarization abnormalities such as a flat or negative T wave as well as the presence of QRS abnormalities, such as conduction disorders or sequelae of necrosis. The abnormalities were compared with the presence and severity of the pericardial reaction on ultrasonography and in the revascularized territories. Two-thirds of patients presented repolarization abnormalities in the anteroseptoapical (ASA) territory, regardless of the intensity of the pericardial reaction. 88% of patients with no QRS abnormalities (75 patients), had an ASA repolarization abnormality. 80% of patients presenting sequelae of isolated inferior necrosis had normal ASA repolarization. The intensity of the pericardial reaction does not determine the presence of postoperative repolarization abnormalities, but rather "myocardial" abnormalities and especially sequelae of inferior necrosis which "normalize" ASA repolarization in 80% of cases, which raises a doubt about the mechanism of these repolarization abnormalities.

Arrhythmias, Cardiac↗
PubMed1997

[Isolated congenital diverticulum of the left ventricle disclosed by ventricular tachycardia in a 72-year-old woman].

A 72-year-old woman presented with poorly tolerated ventricular tachycardia reduced by intravenous amiodarone. The possibility of an ischaemic aetiology led us to perform coronary angiography. The coronary arteries were pathological. Left ventricular angiography revealed limited anterior hypokinesia and a large contractile apical pouch appended to the left ventricle by a long narrow neck. Despite the appearance suggestive of congenital left ventricular diverticulum (contractility, narrow neck) and because of the coexistence of ischaemic heart disease, we preferred to confirm the muscular nature of the diverticulum by myocardial thallium scintigraphy, which showed reversible decreased uptake in the anterior zone related to coronary artery disease, and confirmed the muscular nature of the diverticulum which showed normal thallium uptake. MRI clearly visualized the ventricular ectasia attached by a narrow neck to the rest the left ventricle. This long narrow neck indicated that this muscular diverticulum constituted a congenital diverticulum. The contribution of ultrasonography was limited by a poorly defined point during the examination. This congenital diverticulum, discover during adulthood, and previously asymptomatic, is a rare lesion, in the light of a review of the literature.

Aged↗
PubMed1996

The caudal-related homeodomain protein Cdx-2/3 regulates glucagon gene expression in islet cells.

Glucagon gene transcription in the endocrine pancreas is regulated by at least four cis-acting DNA control elements. We showed previously that G1 is critical for alpha cell-specific expression. G1 contains three AT-rich sequences important for promoter function, which represent candidate binding sites for homeodomain transcription factors. Performing reverse transcription-polymerase chain reaction amplifications with degenerate oligonucleotide primers homologous to the Antennapedia homeobox, cDNA clones corresponding to the caudal-related gene cdx-2/3 were predominantly obtained from glucagon-producing cells and primary non-beta cells. From RNase protection and polymerase chain reaction analyses, cdx-2/3 turned out to be the only caudal-related gene that is expressed at significant levels in cells of the endocrine pancreas. Cdx-2/3 binds with high affinity to an AT-rich motif of G1, which matches the consensus binding site of caudal-related proteins. In the glucagon-producing hamster cell line InR1G9, Cdx-2/3 is a subunit of complex B3 formed on G1. Alternative splicing generates two cdx-2/3 transcripts in islet cells, coding for a full-length protein and an amino-terminally truncated isoform. Although both isoforms bind G1 with similar affinity, only the full-length Cdx-2/3 A protein activates glucagon gene transcription in non-glucagon-producing cells, transcriptional activation being dose-dependent. We therefore conclude that the caudal-related gene cdx-2/3 is implicated in the transcriptional control of glucagon gene expression in the alpha cells of the islets of Langerhans.

Alternative Splicing↗
PubMed1996

Transcriptional induction of the human renin gene by cyclic AMP requires cyclic AMP response element-binding protein (CREB) and a factor binding a pituitary-specific trans-acting factor (Pit-1) motif.

To delineate the cis-acting elements of the proximal promoter responsible for cyclic AMP (cAMP)-induced human renin gene transcription, 5'-flanking regions of the human renin gene were fused to a luciferase reporter gene and transfected in chorionic cells. Forskolin treatment induced the expression of luciferase by 2.4-fold when the reporter plasmid contained the promoter region (-582 to + 16). Mutation or deletion of the cAMP response element (CRE) diminished (1.7-fold) but did not abolish cAMP-induced transcription, demonstrating that the (-582 to -145) region containing the CRE and the region (-145 to -38) containing a Pit-1 (pituitary-specific trans-acting factor) site were both necessary for cAMP maximal induction. To study the molecular events mediating the cAMP induction, DNase I footprinting and electromobility shift assays (EMSAs) were performed with renin-producing chorionic cell and kidney cortex cell nuclear extracts, showing that the CRE-binding protein (CREB) interacts with the CRE and that tissue-specific factors, distinct from Pit-1, specifically bind the renin Pit-1 motif. Taken together, these results demonstrate that the cAMP response of the human renin gene may involve CREB binding the CRE and tissue-specific factors, different from Pit-1, that interact with the Pit-1 response DNA elements.

Base Sequence↗
PubMed1996

Evidence that renal and chorionic tissues contain similar nuclear binding proteins that recognize the human renin promoter.

This study examines whether the human renal cortex, the major renin producing site, contains nuclear factors that bind to the human renin proximal promoter. Footprint analysis of the human renin promoter region showed that human renal cortex cell nuclear extracts interacted with 6 putative cis-elements (the Ets domain-protein, a Pit-1 like binding site, a CRE sequence, an ARP-1 like binding site, an AGE3 like region, and a unknown consensus region, designated element C). Transient DNA transfection studies on chorionic cells implicated the CRE and Pit-1 consensus sites in the regulation of renin gene transcription by cAMP. Electromobility shift assays showed that renal proteins bind specifically to these sequences, and that one of them is CREB; two others seem to be Ets-1 and ARP-1. These results raise the possibility that the human renal cortex and human chorionic cells have the same trans-acting factors that bind to the proximal human renin promoter.

Base Sequence↗
PubMed1996

Insulin gene: organisation, expression and regulation.

Insulin, a major hormone of the endocrine pancreas, plays a key role in the control of glucose homeostasis. This review discusses the mechanisms of cell-specific expression and regulation of the insulin gene. Whereas expression is restricted to islet beta-cells in adults, the insulin gene is more widely expressed at several embryonic stages, although the role of extrapancreatic expression is still unclear. beta-cell-specific expression relies on the interactions of 5'-flanking sequence motifs of the promoter with a number of ubiquitous and islet-specific transcription factors. IEF1 and IPF-1, by their binding to the E and A boxes, respectively, of the insulin gene promoter, appear to be the major determinants of beta-cell-specific expression. IEF1 is a heterodimer of the basic helix-loop-helix family of transcription factors, whereas IPF-1 belongs to the homeodomain-containing family. beta-cell specific determinants are conserved throughout evolution, although the human insulin gene 5'-flanking sequence also contains a polymorphic minisatellite which is unique to primates and may play a role in insulin gene regulation. Glucose modulates insulin gene transcription, with multiple elements of the promoter involved in glucose responsiveness. Remarkably, IPF-1 and IEF1 are involved in both beta-cell-specific expression and glucose regulation of the insulin gene. cAMP also regulates insulin gene transcription through a CRE, in response to various hormonal stimuli. On the whole, recent studies have provided a better understanding of beta-cell differentiation and function.

Adult↗
PubMed1996

[Restenosis on coronary endoprosthesis: treatment by implantation of a new endoprosthesis. Apropos of a case].

A 60-year-old man was admitted to hospital with threatened anterior myocardial infarction due to double tight stenosis in the 1st and 2nd segments of the left anterior descending artery. This double stenosis was successfully treated, without any complications, by two Palmatz-Schatz 15.4 mm (PS 154 A) coronary stents. He was readmitted to hospital six months later for another episode of threatened anterior infarction, due to restenosis involving the 2 coronary stents. Balloon angioplasty of this restenosis was attempted, but the poor result led us to insert 2 contiguous articulated Palmatz-Schatz 154 mm stents (PS 154 A) inside the previous two stents. The result was excellent with no complications apart from distal dissection induced by the guide, requiring insertion of an AVE Stent, 8 mm long and 3 mm in diameter. An exercising myocardial scintigraphy performed one month after the procedure was normal. The patient is still asymptomatic with a follow-up of 6 months. The feasibility and low risk of complication of balloon angioplasty in the case of restenosis, after insertion of an intracoronary stent have been demonstrated by several studies. To our knowledge, no case of restenosis of an intracoronary stent, treated by insertion of a new stent, have been reported. We report a case of restenosis on two Palmatz-Schatz stents successfully treated by insertion of two contiguous PS 154 A stents.

Angioplasty, Balloon, Coronary↗
PubMed1995

Islet-specific proteins interact with the insulin-response element of the glucagon gene.

Glucagon gene expression is negatively regulated by insulin at the transcriptional level. G3, a DNA control element located in the 5'-flanking sequence of the rat glucagon gene mediates the inhibition of transcription, which occurs in response to insulin. We show here that two islet-specific protein complexes C1A and C1B, bind to the A domain of G3, which is critical for the insulin response. These two complexes bind to overlapping sequences of the A domain and display very similar binding specificities. Point mutations in the A domain that affect binding of C1A and C1B result in both decreased G3 enhancer activity and insulin-mediated inhibitory effects with a close correlation between diminution of binding and function. One of the two complexes, C1A, is similar or identical to B1, a protein complexes interacting with the upstream promoter element of the glucagon gene, G1, implicated in the A cell-specific expression of the glucagon gene. Our data indicate that islet-specific proteins are involved in glucagon gene regulation by insulin.

Animals↗
PubMed1995

The upstream promoter element of the glucagon gene, G1, confers pancreatic alpha cell-specific expression.

The glucagon gene is expressed in the endocrine pancreas, the intestine, and the brain. In the endocrine pancreas, expression of the glucagon gene is restricted to the alpha cells of the islets of Langerhans. We previously showed that 168 base pairs of the promoter was critical for this restricted expression. To further characterize the mechanisms involved in alpha cell specificity, we analyzed the responsible DNA sequences by transient transfection studies into glucagon- and insulin-producing cell lines. We localized alpha cell-specific sequences between nt 100 and 52, a region that corresponds to the upstream promoter element G1. Four protein complexes, B1, B2, B3, and B6 interact with G1; B6 requires most of G1 to be formed. B1, B2, and B3, by contrast, bind on closely overlapping sequences, display similar methylation interference patterns, and appear to be related complexes. Point mutations of G1 indicate, however, that their binding specificities are different. All four complexes are islet-specific, and impairment of their binding results in decreased transcription. We conclude that G1 interacts with islet cell-specific proteins to restrict glucagon gene expression to the alpha cells.

Alkaline Phosphatase↗
PubMed1995

Adequate connexin-mediated coupling is required for proper insulin production.

To assess whether connexin (Cx) expression contributes to insulin secretion, we have investigated normal and tumoral insulin-producing cells for connexins, gap junctions, and coupling. We have found that the glucose-sensitive cells of pancreatic islets and of a rat insulinoma are functionally coupled by gap junctions made of Cx43. In contrast, cells of several lines secreting insulin abnormally do not express Cx43, gap junctions, and coupling. After correction of these defects by stable transfection of Cx43 cDNA, cells expressing modest levels of Cx43 and coupling, as observed in native beta-cells, showed an expression of the insulin gene and an insulin content that were markedly elevated, compared with those observed in both wild-type (uncoupled) cells and in transfected cells overexpressing Cx43. These findings indicate that adequate levels of Cx-mediated coupling are required for proper insulin production and storage.

Animals↗
PubMed1995

Carbamazepine hypersensitivity syndrome: report of 4 cases and review of the literature.

We report 4 patients who developed a severe systemic hypersensitivity reaction when taking carbamazepine, To prove hypersensitivity to carbamazepine, we performed patch tests and in vitro lymphocyte transformation tests. Patch tests were uniformly and strongly positive in patients and negative in controls. Lymphocyte transformation tests were positive in 3 of 4 patients. We reviewed the literature on reports of carbamazepine-induced pseudolymphoma and other severe systemic hypersensitivity reactions. Considering the many common clinical, biochemical, and pathologic characteristics, we propose to group these reactions under the term "carbamazepine hypersensitivity syndrome." The syndrome is characterized by the development of fever, rash, and lymphadenopathy between 1 week and 3 months after the introduction of carbamazepine. A variety of other target organs may be involved, including the liver, kidneys, and lungs. The carbamazepine hypersensitivity syndrome is a clinical diagnosis. Patch tests and lymphocyte transformation tests are valuable tools to confirm the diagnosis, but are reliable only after all signs subside. Similar syndromes have been described with the other aromatic anticonvulsants (phenytoin, the other hydantoins, and phenobarbital), and there is evidence of a cross-reaction between carbamazepine and phenytoin. It is unknown whether the carbamazepine hypersensitivity syndrome should be considered a premalignant state, with an increased risk for the development of malignant lymphoma.

Adult↗
PubMed1995

Homologous DNA sequences and cellular factors are implicated in the control of glucagon and insulin gene expression.

The glucagon gene is specifically expressed in the alpha cells of pancreatic islets. The promoter of the glucagon gene is responsible for this specificity. Within the promoter, the upstream promoter element G1 is critical to restrict expression to the alpha cells. We define here a composite DNA control element, G4, localized upstream of G1 between nucleotides -100 and -140 which functions as an islet-specific activator in both glucagon- and insulin-producing cells but not in nonislet cells. G4 contains at least three protein binding sites. The most proximal site, E2, is highly homologous to the E1, SMS-UE, and B elements of the rat insulin I, somastatin, and elastase I genes, respectively, and interacts with a pancreas-specific complex; the distal site, E3, represents an E box which is identical to the E boxes of the rat insulin I and II genes and binds to a complex similar or identical to IEF1 which has been implicated in the tissue-specific control of insulin gene expression. These two sites necessitate a third element, the intervening sequence, to activate transcription. We conclude that the first 140 bp of the glucagon gene promoter contains at least two DNA control elements responsible for pancreatic alpha-cell-specific expression: G4, an islet cell-specific element sharing common binding sites with the insulin gene, and G1, which restricts glucagon gene expression to the alpha cells. This double control of specificity might have relevance during islet cell differentiation.

Animals↗
PubMed1995

In vivo effects of glucose and insulin on secretion and gene expression of glucagon in rats.

We investigated the effects of insulin and glucose on the control of secretion and gene expression of glucagon in vivo in rats. Animals were studied during 1) a 48-h period of either glucose infusion (hyperglycemia plus hyperinsulinemia; HG-HI rats) or insulin infusion (euglycemia plus hyperinsulinemia; EG-HI rats), and 2) a prolonged postinfusion period in both groups. In HG-HI rats, elevation of plasma insulin and glucose concentrations by about 7 and 5 times, respectively, resulted in a decline in glucagon levels, which fell significantly within 6 h and remained low thereafter, whereas these levels were unchanged in EG-HI rats. Glucagon messenger RNA levels and pancreatic glucagon content were not significantly affected in either HG-HI or EG-HI rats. After cessation of infusions, hypoglycemia occurred in both group of rats. In HG-HI rats, hypoglycemia lasted for about 36 h without any surge in the plasma glucagon level, whereas in EG-HI rats it was transient (approximately 1 h) and stimulated glucagon secretion. In both groups the pancreatic alpha-cell was unresponsive to arginine during the postinfusion period. In conclusion, although a role of intraislet insulin cannot be excluded, glucagon gene expression is insensitive to changes in plasma glucose and insulin concentrations. In contrast, hyperglycemia/hyperinsulinemia, not hyperinsulinemia alone, lowers glucagon secretion and affects the alpha-cell responsiveness to hypoglycemia.

Animals↗
PubMed1995

Hepatocyte-nuclear factor 3 beta gene transcripts generate protein isoforms with different transactivation properties on the glucagon gene.

Hepatocyte-nuclear factor 3 beta (HNF-3 beta), a member of the HNF-3 gene family, is expressed in glucagon-producing islet cells and represses glucagon gene expression. We show here that at least three different HNF-3 beta transcripts that encode HNF-3 beta protein variants are present in glucagon-producing cells, HNF-3 beta 1, HNF-3 beta 2, and HNF-3 beta 3. Compared with the HNF-3 beta 1 cDNA, HNF-3 beta 2 cDNA lacks sequences of exon 1 while exons 1 and 4 are absent from the HNF-3 beta 3 cDNA. The deduced amino-acid (aa) sequence of HNF-3 beta 2 and HNF-3 beta 3 proteins differs from HNF-3 beta 1 by a 6-aa amino-terminal extension and by the absence of the first 30 aa, respectively. HNF-3 beta 1, HNF-3 beta 2, and HNF-3 beta 3 bind to the major enhancer of the rat glucagon gene G2 with similar affinity. By contrast to HNF-3 beta 1, which represses glucagon gene expression when overexpressed in the glucagon-producing cell line InR1G9, HNF-3 beta 2 and HNF-3 beta 3 do not affect transcriptional activity. Furthermore, cotransfection of HNF-3 beta 2 or HNF-3 beta 3 along with HNF-3 beta 1 decreases the negative effects of HNF-3 beta 1. We conclude that glucagon gene expression may be regulated by the relative abundance of the three different HNF-3 beta variants in alpha-cells.

Amino Acid Sequence↗
PubMed1995

Long-lasting effects of Triac and thyroxine on the control of thyrotropin and hepatic deiodinase type I.

The purpose of this study was to investigate the relation between the serum levels of thyroid hormones and their biological effects. For this purpose, hypothyroid rats were studied after stopping treatment with a long-acting thyroid hormone, thyroxine (T4) and a short-acting one, triiodothyroacetic acid (Triac). Based on preliminary experiments with different doses of T4 and Triac, hypothyroid rats (N = 84) received over 6 days' injections of 10 nmol Triac or 2 nmol T4/100 g body wt per day. Biological effects of Triac and T4 were measured in the pituitary, liver and kidney up to 8 days after stopping treatment. With Triac, serum thyrotropin (TSH) levels were inhibited completely 6 h after injection, yet after 24 h they were 4.9 +/- 1.8 micrograms/l (hypothyroid 14.5 +/- 0.8 micrograms/l). The rapid changes in serum TSH levels were followed by a more gradual increase in serum TSH levels were followed by a more gradual increase in serum TSH, which was similar to that after T4 injection. Even 8 days after Triac treatment, serum TSH levels did not reach the hypothyroid control levels. Changes in beta-TSH mRNA levels also showed a prolonged inhibition after both treatments and a slow return to hypothyroid values, which was not complete 8 days after stopping treatment. A second parameter was hepatic 5'-deiodinase type I (5'D-I). The 6-day treatment with Triac had a markedly stronger effect on 5'D-I enzyme activity and mRNA levels than treatment with T4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗