Early ischemic ST-segment and T-wave changes during balloon angioplasty.

Background: Acute coronary occlusion results in increased T-wave amplitude and ST-segment elevation in the ECG leads facing the ischemic region.

Material And Methods: We performed continuous ECG recording in 34 patients during balloon occlusion of the left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA). Delta (Δ) ST and ΔT amplitudes were calculated by subtracting the preinflation values from the values measured during balloon inflation.

AGN as potential factories for eccentric black hole mergers.

There is some weak evidence that the black hole merger named GW190521 had a non-zero eccentricity. In addition, the masses of the component black holes exceeded the limit predicted by stellar evolution. The large masses can be explained by successive mergers, which may be efficient in gas disks surrounding active galactic nuclei, but it is difficult to maintain an eccentric orbit all the way to the merger, as basic physics would argue for circularization.

Local model for angular-momentum transport in accretion disks driven by the magnetorotational instability.

We develop a local model for the exponential growth and saturation of the Reynolds and Maxwell stresses in turbulent flows driven by the magnetorotational instability. We first derive equations that describe the effects of the instability on the growth and pumping of the stresses. We highlight the relevance of a new type of correlations that couples the dynamical evolution of the Reynolds and Maxwell stresses and plays a key role in developing and sustaining the magnetorotational turbulence.

Nuclear retention of the tumor suppressor cPML by the homeodomain protein TGIF restricts TGF-beta signaling.

The homeodomain protein TGIF has been implicated in the negative regulation of TGF-beta signaling. In this study, we report an unexpected role of TGIF in the inhibition of Smad2 phosphorylation, which occurs by a mechanism independent of its association with Smad2. This inhibitory function of TGIF is executed in concert with c-Jun, which facilitates the interaction of TGIF with cPML, resulting in the nuclear sequestration of cPML and the disruption of the cPML-SARA complex.

AIP4 restricts transforming growth factor-beta signaling through a ubiquitination-independent mechanism.

Smad7 functions as an intracellular antagonist in transforming growth factor-beta (TGF-beta) signaling. In addition to interacting stably with the activated TGF-beta type I receptor (TbetaRI) to prevent phosphorylation of the receptor-regulated Smads (Smad2 and Smad3), Smad7 also induces degradation of the activated TbetaRI through association with different E3 ubiquitin ligases. Using the two-hybrid screen, we identified atrophin 1-interacting protein 4 (AIP4) as an E3 ubiquitin ligase that specifically targets Smad7 for ubiquitin-dependent degradation without affecting the turnover of the activated TbetaRI.

The novel E3 ubiquitin ligase Tiul1 associates with TGIF to target Smad2 for degradation.

Ubiquitin-dependent degradation plays an important role in the negative regulation of TGF-beta signaling. Here, we identify Tiul1 (for TGIF interacting ubiquitin ligase 1), a novel E3 ubiquitin ligase that inhibits TGF-beta signaling by targeting both the activated receptor and Smad2 for degradation. Tiul1 associates constitutively with Smad7 and induces degradation of the activated type I receptor without affecting the expression levels of Smad7.

The oncoprotein Ski acts as an antagonist of transforming growth factor-beta signaling by suppressing Smad2 phosphorylation.

The phosphorylation of Smad2 and Smad3 by the transforming growth factor (TGF)-beta-activated receptor kinases and their subsequent heterodimerization with Smad4 and translocation to the nucleus form the basis for a model how Smad proteins work to transmit TGF-beta signals. The transcriptional activity of Smad2-Smad4 or Smad3-Smad4 complexes can be limited by the corepressor Ski, which is believed to interact with Smad complexes on TGF-beta-responsive promoters and represses their ability to activate TGF-beta target genes by assembling on DNA a repressor complex containing histone deacetylase. Here we show that Ski can block TGF-beta signaling by interfering with the phosphorylation of Smad2 and Smad3 by the activated TGF-beta type I receptor.

c-Jun associates with the oncoprotein Ski and suppresses Smad2 transcriptional activity.

The Smad proteins are key intracellular effectors of transforming growth factor-beta (TGF-beta) cytokines. The ability of Smads to modulate transcription results from a functional cooperativity with the coactivators p300/cAMP-response element-binding protein-binding protein (CBP), or the corepressors TGIF and Ski. The c-Jun N-terminal kinase (JNK) pathway, another downstream target activated by TGF-beta receptors, has also been suggested to inhibit TGF-beta signaling through interaction of c-Jun with Smad2 and Smad3.

Evidence for a role of the JNK cascade in Smad7-mediated apoptosis.

Smad proteins are central mediators of the transcriptional effects of transforming growth factor beta (TGF-beta) superfamily that regulate a wide variety of biological processes. Smad7, an inhibitory Smad protein that prevents TGF-beta signaling by interacting with the activated type I TGF-beta receptor, was recently shown to induce sensitization of cells to different forms of cell death. Here we examined the effect of Smad7 on the c-Jun N-terminal kinase (JNK) cascade and investigated the role of this cascade in both the inhibitory and apoptotic functions of Smad7.

c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity.

The Sma and Mad related (Smad) family proteins are critical mediators of the transforming growth factor-beta (TGF-beta) superfamily signaling. After TGF-beta-mediated phosphorylation and association with Smad4, Smad2 moves to the nucleus and activates expression of specific genes through cooperative interactions with DNA-binding proteins, including members of the winged-helix family of transcription factors, forkhead activin signal transducer (FAST)-1 and FAST2. TGF-beta has also been described to activate other signaling pathways, such as the c-Jun N-terminal Kinase (JNK) pathway.

Mechanism for mutational inactivation of the tumor suppressor Smad2.

Transforming growth factor beta (TGF-beta) is a potent natural antiproliferative agent that plays an important role in suppressing tumorigenicity. In numerous tumors, loss of TGF-beta responsiveness is associated with inactivating mutations that can occur in components of this signaling pathway, such as the tumor suppressor Smad2. Although a general framework for how Smads transduce TGF-beta signals has been proposed, the physiological relevance of alterations of Smad2 functions in promoting tumorigenesis is still unknown.

Tumor necrosis factor-alpha inhibits transforming growth factor-beta /Smad signaling in human dermal fibroblasts via AP-1 activation.

Understanding the molecular mechanisms underlying the antagonistic activities of tumor necrosis factor-alpha (TNF-alpha) against transforming growth factor-beta (TGF-beta) is of utmost importance given the physiopathological implications of these cytokines. In this report, we demonstrate that TNF-alpha prevents TGF-beta-induced Smad-specific gene transactivation without inducing detectable levels of inhibitory Smad7 in human dermal fibroblasts. On the other hand, c-Jun and JunB, both induced by TNF-alpha, block Smad3-mediated transcription.

Decreased ADP-ribosylation of the Galpha(olf) and Galpha(s) subunits by high glucose in pancreatic B-cells.

In HIT-T15 insulinoma B-cells incubated in presence of [(32)P]NAD, we identified by autoradiography and immunoblotting ADP-ribosylation (ADP-R) of the trimeric G-protein Galpha(s) and Galpha(olf) subunits (45 kDa) induced by cholera toxin in M1 (120,000g) and M2 (70,000g) subcellular fractions containing plasma membranes, insulin granules, and mitochondria. This ADP-R indicates that these two fractions contain functionally competent Galpha subunits for adenylyl cyclase activation. Prolonged exposure of HIT-T15 cells to high glucose (25 mM instead of 6 mM) specifically reduced the ADP-R in Galpha(s) and Galpha(olf) subunits in the M1 fraction only, despite the clear increase of their accumulation in this compartment.

Olfactory receptors, Golf alpha and adenylyl cyclase mRNA expressions in the rat heart during ontogenic development.

Golf alpha (a G heterotrimeric protein which shares a high homology with Gs alpha) expression was studied in the rat heart before birth and until weaning. Since Golf alpha in the neuro-olfactory epithelium is coupled to olfactory receptors and type III adenylyl cyclase, we looked for the presence of such molecules in the heart. Golf alpha mRNA was detected in the rat heart, highest levels being found in 21-day old fetuses until 3 days post partum.

Stimulatory transducing systems in pancreatic islet cells.

We have determined the cellular distribution of different alpha subtypes of G proteins and adenylyl cyclase (AC) isoforms in endocrine, exocrine, and established pancreatic cell lines. VIP, PACAP, and tGLP-1 receptor proteins are expressed to varying extents in A and B cells, whereas the expression of G alpha subunits is cell specific. Thus, G(olf) alpha is detected in normal rodent B cells and immortalized pancreatic B cell lines, whereas Gs alpha is more ubiquitously expressed.

Galphaolf identification by RT-PCR in purified normal pancreatic B cells and in islets from rat models of non-insulin-dependent diabetes.

Recent reports using immunohistochemistry have shown that Galphaolf which shares 88% homology with Galphas was expressed in pancreatic islets. To test the specificity of the expression of this G protein isotype in rat islet cells, B and non-B cells were separated by flow cytometry. The expression of Galphaolf and adenylyl cyclases (AC) of types II, III, V, and VI was evaluated by reverse-transcriptase polymerase chain reaction (RT-PCR).

GLP-1 receptors in golden Syrian hamster islets: identification and functional characterization.

This study aims at the identification and functional characterization of glucagon-like peptide 1 (7-36) amide (GLP-1) receptor in islets from Golden Syrian hamsters. Using a polyclonal antibody against rat GLP-1 receptors, Western blotting of the islet proteins revealed two major bands of 44 and 70 kDa, similar to those found in rat islets, RINm5F cells, and HIT-T15 cells. In Northern blots, transcripts of 2.

Chylomicron retention disease: exclusion of apolipoprotein B gene defects and detection of mRNA editing in an affected family.

Chylomicron retention disease (CRD) is a rare autosomal recessive disorder characterized by the absence of post-prandial chylomicrons and apolipoprotein (apo) B-48 in sera from affected individuals. Apo B-100 is synthesized, and apo B-100-containing lipoproteins are present in sera. A crucial difference between the synthesis and secretion of apo B-containing lipoproteins from the liver and gut in man is the generation of apo B-48 by editing of apo B mRNA in the gut to create a premature stop-translation codon.

Donor splice mutation generates a lipid-associated apolipoprotein B-27.6 in a patient with homozygous hypobetalipoproteinemia.

We report the characterization of a new truncated apolipoprotein (apo) B, originally identified in the plasma of a homozygous proband and three heterozygous family members with hypobetalipoproteinemia. Using Western blotting, the truncated apoB species was estimated to be 27.5% the size of apoB-100.

Genetic exclusion of apo-B gene in recessive abetalipoproteinemia.

Abetalipoproteinemia is a recessive genetic disorder of unknown origin, which is characterized by absence of circulating apo-B-containing lipoproteins, malabsorption of intestinal fat, and degenerative neurological and retinal lesions. In this study, four families were analysed for genetic linkage between the abetalipoproteinemia phenotype and the apo-B genotype determined from polymorphisms of XbaI, MsPI, EcoRI and PvuII restriction sites and that of the 3'-minisatellite of the apo-B gene. The results definitively exclude mutation of the apo-B gene as a causal factor of abetalipoproteinemia in three families.

Modification of the amount of cholesterol in hepatic steatosis induced in susceptible and resistant mice infected with MHV3: a biochemical and ultrastructural study.

A mouse hepatitis virus-3 strain subcultured in our laboratory is a unique experimental model in which to study virus-induced liver steatosis. This strain produces massive lipid deposition not only in sensitive adult BALB/c mice but also (though less extensive) in virus-resistant adult A/J mice. Biochemical determinations have shown that this steatosis is characterized by an increased amount of neutral lipids (sterols and triglycerides) in infected livers of BALB/c mice and by a smaller increase in those of A/J mice.

Anderson's disease: genetic exclusion of the apolipoprotein-B gene in two families.

Anderson's disease is a recessive disorder characterized by intestinal fat malabsorption, absence of postprandial chylomicrons, and reduced levels of cholesterol, triglycerides, and apoproteins B, AI, and C. We have studied two families with, respectively, three and two children with Anderson's disease. Intestinal apo-B and apo-AIV mRNAs from two Anderson's patients were normal in size but their concentration was decreased fivefold compared with controls.

[Familial hypobetalipoproteinemia. Familial study of 4 cases].

A familial study of four cases with hypobetalipoproteinemia is reported. Three members are heterozygous and one is homozygous. This congenital fat malabsorption in homozygous state is commonly associated with an absence of serum apoprotein B and LDL.

Description of two different patients with abetalipoproteinemia: synthesis of a normal-sized apolipoprotein B-48 in intestinal organ culture.

We describe here two patients, M. P. and S.

Lipid and lipoprotein metabolism in Hep G2 cells.

Lipid composition, lipid synthesis and lipoprotein secretion by the Hep G2 cell line have been studied with substrate and insulin supplied under different conditions. The lipid composition of Hep G2 cells was close to that of normal human liver, except for a higher content in sphingomyelin (P less than 0.005) and a lower phosphatidylcholine/sphingomyelin ratio.