Deletion of 3'CBFbeta in an inv(16)(p13.lq22) ascertained by fluorescence in situ hybridization and reverse-transcriptase polymerase chain reaction.
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3' Untranslated Regions↗
Biomedical subjects
D Hung
Publications and source records attributed to D Hung.
Membrane binding proteins are the major determinants for the hepatocellular transmembrane flux of long-chain fatty acids bound to albumin.
PURPOSE: The hepatic transmembrane flux of long-chain fatty acids (LCFA) occurs through passive and fatty acid transport protein facilitated processes from blood. The extent that these transport processes can be related to the unbound and protein-bound fractions of LCFA in blood is not clear. METHODS: We used hepatocyte suspensions, hepatoma monolayers, and perfused rat livers to quantitate the transport of purified [(3)H]palmitate ([(3)H]PA) and 12-(N-methyl)-N-[(7-nitrobenz-2oxa-1,3-diazol-4yl-)amino]octadecanoicacid (12-NBDS) from solutions with a constant unbound LCFA concentration with varying bovine serum albumin (BSA) concentrations and in the presence and absence of antisera raised against cytosolic liver fatty acid binding protein (L-FABP). RESULTS: In the absence of L-FABP antisera, using an unbound ligand concentration that was adjusted to remain constant at each BSA concentration, hepatocyte [(3)H]PA and 12-NBDS uptake rates increased linearly with an increase in BSA concentration (p < 0.0001). In the presence of L-FABP antisera, [(3)H]PA uptake showed a greater reduction in the presence of 100 muM BSA than 5 muM BSA. The calculated permeability surface area product (PS) confirmed that both unbound and bound fractions of LCFA contributed to the overall flux, but only the PS for the protein-bound fraction was reduced in the presence of L-FABP antisera. In situ rat liver perfusion studies showed that the only rate process for the disposition of [(3)H]PA in the liver inhibited by L-FABP antisera was that for influx, as defined by PS, and that it reduced PS in the perfused liver by 42%. CONCLUSION: These results suggest that, at physiological albumin concentrations, most of the LCFA uptake is mediated from that bound to albumin by a hepatocyte basolateral membrane transport protein, and uptake of unbound LCFA occurring by passive diffusion contributes a minor component.
Albumins↗
Assessing the cellular transmembrane electrical potential difference on the hepatic uptake of palmitate.
Understanding the driving forces for the hepatic uptake of endogenous and exogenous substrates in isolated cells and organs is fundamental to describing the underlying hepatic physiology/pharmacology. In this study we investigated whether uptake of plasma protein-bound [3H]-palmitate across the hepatocyte wall is governed by the transmembrane electrical potential difference (PD). Uptake was studied in isolated hepatocytes and isolated perfused rat livers (IPL). Protein-binding and vasoactive properties of the different perfusates were determined using in vitro heptane/buffer partitioning studies and the multiple indicator dilution (MID) technique in the IPL, respectively. Altering hepatocyte PD by perfusate ion substitution resulted in either a substantial depolarization (-14 +/- 1 mV, n = 12, mean +/- S.E., substituting choline for Na+) or hyperpolarization (-46 +/- 3 mV, n = 12, mean +/- S.E., substituting nitrate for Cl-). Perfusate ion substitution also affected the equilibrium binding constant for the palmitate-albumin complex. IPL studies suggested that, other than with gluconate buffer, hepatic [3H]-palmitate extraction was not affected by the buffer used, implying PD was not a determinant of extraction. [3H]-Palmitate extraction was much lower (p < 0.05) when gluconate was substituted for Cl- ion. This work contrasts with that for the extraction of [3H]-alanine where hepatic extraction fraction was significantly reduced during depolarization. Changing the albumin concentration did not affect hepatocyte PD, and [3H]-palmitate clearance into isolated hepatocytes was not affected by the buffers used. MID studies with vascular and extravascular references revealed that, with the gluconate substituted buffer, the extravascular volume possibly increased the diffusional path length thus explaining reduced [3H]-palmitate extraction fraction in the IPL.
Alanine↗
A left-lateralized network for reading Chinese words: a 3 T fMRI study.
fMRI was used to investigate brain organization for reading in Chinese. Subjects were shown two-character Chinese words. A control task was used to eliminate the non-linguistic visual and motor confounds. Results show that naming of Chinese logographs is characterized by left-lateralized neuronal networks for the processing of orthographic, phonological, and semantic attributes. The orchestration of the middle frontal cortex, superior temporal cortex, superior parietal cortex, basal temporal area and extrastriate cortices of the left hemisphere may manifest the particularity of the central representation of simple word naming in Chinese.
Adult↗
Dynamic localization of a cytoplasmic signal transduction response regulator controls morphogenesis during the Caulobacter cell cycle.
We present evidence that a bacterial signal transduction cascade that couples morphogenesis with cell cycle progression is regulated by dynamic localization of its components. Previous studies have implicated two histidine kinases, DivJ and PleC, and the response regulator, DivK, in the regulation of morphogenesis in the dimorphic bacterium Caulobacter crescentus. Here, we show that the cytoplasmic response regulator, DivK, exhibits a dynamic, cyclical localization that culminates in asymmetric distribution of DivK within the two cell types that are characteristic of the Caulobacter cell cycle; DivK is dispersed throughout the cytoplasm of the progeny swarmer cell and is localized to the pole of the stalked cell. The membrane-bound DivJ and PleC histidine kinases, which are asymmetrically localized at the opposite poles of the predivisional cell, control the temporal and spatial localization of DivK. DivJ mediates DivK targeting to the poles whereas PleC controls its release from one of the poles at times and places that are consistent with the activities and location of DivJ and PleC in the late predivisional cell. Thus, dynamic changes in subcellular location of multiple components of a signal transduction cascade may constitute a novel mode of prokaryotic regulation to generate and maintain cellular asymmetry.
Bacterial Proteins↗
Syntactic priming of nouns and verbs in Chinese.
Syntactic priming of Chinese nouns and verbs was investigated in word recognition (cued shadowing of auditory targets) and production (picture naming). Disyllabic compound words were presented after syntactically congruent, incongruent, or neutral auditory contexts, with a zero delay between offset of the context and onset of the target. Significant priming was observed in both tasks, including facilitation as well as inhibition. Post hoc analyses showed that reaction times were also affected by sublexical variables that are especially relevant for Chinese, including syllable density (number of word types and tokens in the language with the same first or second syllable) and semantic transparency (whether the meaning of the whole word is predictable from the separate meanings of the two syllables within the compound). These patterns suggest competitive effects at the sublexical level. Implications for interactive models of lexical access are discussed.
Cues↗
Insulin receptors and insulin action in the brain: review and clinical implications.
Insulin receptors are known to be located on nerve cells in mammalian brain. The binding of insulin to dimerized receptors stimulates specialized transporter proteins that mediate the facilitated influx of glucose. However, neurons possess other mechanisms by which they obtain glucose, including transporters that are not insulin-dependent. Further, insulin receptors are unevenly distributed throughout the brain (with particularly high density in choroid plexus, olfactory bulb and regions of the striatum and cerebral cortex). Such factors imply that insulin, and insulin receptors, might have functions within the central nervous system in addition to those related to the supply of glucose. Indeed, invertebrate insulin-related peptides are synthesized in brain and serve as neurotransmitters or neuromodulators. The present review summarizes the structure, distribution and function of mammalian brain insulin receptors and the possible implications for central nervous system disorders. It is proposed that this is an under-studied subject of investigation.
Animals↗
Distribution of particulate matter and tissue remodeling in the human lung.
We examined the relationship between intrapulmonary particle distribution of carbonaceous and mineral dusts and remodeling of the airways along anatomically distinct airway paths in the lungs of Hispanic males from the central valley of California. Lung autopsy specimens from the Fresno County Coroner's Office were prepared by intratracheal instillation of 2% glutaraldehyde at 30 cm H(2)O pressure. Two distinct airway paths into the apico-posterior and apico-anterior portions of the left upper lung lobe were followed. Tissue samples for histologic analysis were generally taken from the intrapulmonary second, fourth, sixth, and ninth airway generations. Parenchymal tissues beyond the 12th airway generation of each airway path were also analyzed. There was little evidence of visible particle accumulation in the larger conducting airways (generations 2-6), except in bronchial-associated lymphoid tissues and within peribronchial connective tissue. In contrast, terminal and respiratory bronchioles arising from each pathway revealed varying degrees of wall thickening and remodeling. Walls with marked thickening contained moderate to heavy amounts of carbonaceous and mineral dusts. Wall thickening was associated with increases in collagen and interstitial inflammatory cells, including dust-laden macrophages. These changes were significantly greater in first-generation respiratory bronchioles compared to second- and third-generation respiratory bronchioles. These findings suggest that accumulation of carbonaceous and mineral dust in the lungs is significantly affected by lung anatomy with the greatest retention in centers of lung acini. Furthermore, there is significant remodeling of this transitional zone in humans exposed to ambient particulate matter.
Adolescent↗
Intrapericardial delivery of fibroblast growth factor-2 induces neovascularization in a porcine model of chronic myocardial ischemia.
Therapeutic angiogenesis is a novel approach to the treatment of myocardial ischemia based on the use of proangiogenic growth factors to induce the growth of new blood vessels to supply the myocardium at risk. This study was designed to assess the safety and efficacy of a single intrapericardial injection of basic fibroblast growth factor (FGF-2) in a porcine model of chronic myocardial ischemia. Yorkshire pigs underwent ameroid placement around the left circumflex coronary artery. At 3 weeks, animals were randomized to receive a single intrapericardial injection of either saline (n = 10), 3 mg of heparin (n = 9), 3 mg of heparin + 30 microgram of FGF-2 (n = 10), 200 microgram of FGF-2 (n = 10), or 2 mg of FGF-2 (n = 10). Coronary angiography, microsphere flow, magnetic resonance functional, and perfusion imaging were performed before and 4 weeks after treatment, at which time histologic analysis was also performed on 3 animals in each group. In ischemic pigs, FGF-2 treatment resulted in significant increases in left-to-left angiographic collaterals and left circumflex coronary artery blood flow. These benefits were accompanied by improvements in myocardial perfusion and function in the ischemic territory, as well as histologic evidence of increased myocardial vascularity without any adverse effects. Not one of these benefits was seen in saline- or heparin-treated ischemic animals. A single intrapericardial injection of FGF-2 in a porcine model of chronic myocardial ischemia results in functionally significant myocardial angiogenesis, without any adverse outcomes. This mode of FGF-2 administration may prove to be a useful therapeutic strategy for the treatment of patients with ischemic heart disease.
Administration, Topical↗
Subxyphoid access of the normal pericardium: a novel drug delivery technique.
The pericardial space may potentially serve as a drug delivery reservoir that might be used to deliver therapeutic substances to the heart. This study describes a novel delivery technique that enables safe and rapid percutaneous subxyphoid access of the normal pericardium in a large animal model (49 Yorkshire pigs). An epidural introducer needle (Tuohy-17) is advanced gently under fluoroscopic guidance with a continuous positive pressure of 20-30 mm Hg (achieved by saline infusion using an intraflow system). The positive pressure is intended to push the right ventricle (with a lower pressure) away from the needle's path. Entry of the pericardial space is suspected after an increase in the saline flow through the intraflow system. Access to the pericardial space is confirmed by the injection of 1 ml of diluted contrast under fluoroscopy. A soft floppy-tip 0.025" guidewire is then advanced to the pericardial space and the needle is exchanged for an infusion catheter. Access of the pericardial space was achieved in all animals without any adverse events and without any hemodynamic compromise even with the delivery of fluid volumes as large as 50 ml. Histologic examination in 15 animals 4 weeks after pericardial access did not reveal any delivery-related myocardial damage. The safety, ease, and absence of hemodynamic compromise make this technique a potentially useful method for intrapericardial drug delivery and a good alternative to standard pericardiocentesis in patients with small pericardial effusions at higher risk for complications.
Animals↗
Therapeutic myocardial angiogenesis using percutaneous intrapericardial drug delivery.
In this manuscript, we describe the potential role of the pericardial space as a drug delivery reservoir to administer angiogenic agents to the heart resulting in functionally significant angiogenesis with single bolus basic fibroblast growth factor (bFGF) delivery. We also describe a percutaneous subxyphoid pericardial access technique that is safe, rapid, and reliable.
Animals↗
Intracoronary and intravenous administration of basic fibroblast growth factor: myocardial and tissue distribution.
Therapeutic angiogenesis using various heparin-binding growth factors is a promising treatment for ischemic heart disease. Single dose intracoronary (IC) or i.v. delivery are most practical for clinical use. This study was designed to investigate the myocardial and tissue deposition of basic fibroblast growth factor (bFGF) after IC and i.v. administration in normal and chronically ischemic animals. Twenty-four Yorkshire pigs were used (12 normal and 12 ischemic animals) with IC and i.v. administration of 125I-bFGF (25 microCi) combined with cold bFGF (30 microg) and heparin (3 mg). Tissue and myocardial distribution was determined at 1 and 24 h by measuring 125I-bFGF specific activity and by organ and light level autoradiography. The liver accounted for the majority of 125I-bFGF activity at 1 h (37.6 +/- 17.1% for IC and 42.1 +/- 17.7% for i.v. delivery), with a reduction to 2.8 +/- 1.5% for IC and 1.5 +/- 0.9% for i.v. delivery by 24 h. Total cardiac specific activity at 1 h was 0.88 +/- 0.89% for IC and 0.26 +/- 0.08% for i.v. administration (p =.12) and decreased to 0.05 +/- 0.04% (p =.05, versus 1 h) and 0. 04 +/- 0.01% (p <.001, versus 1 h) at 24 h, respectively. IC but not i.v. delivery resulted in higher deposition in ischemic than normal myocardium. IC delivery resulted in enhanced bFGF deposition only in myocardial territories subtended by the infused artery. Intravenous delivery compares favorably with IC delivery with a 3- to 4-fold reduction in myocardial deposition at 1 h and with similar solid organ deposition. The less invasive nature of i.v. delivery, its potential for repeat administration, and its applicability to a larger population may offset its resultant reduced myocardial deposition. Efficacy studies are ongoing.
Animals↗
Modulation of myocardial perfusion and vascular reactivity by pericardial basic fibroblast growth factor: insight into ischemia-induced reduction in endothelium-dependent vasodilatation.
OBJECTIVES: The present study was designed to study the effects of a single intrapericardial injection of basic fibroblast growth factor on myocardial vascular resistance and endothelium-dependent microvascular dilatation in a porcine model of chronic myocardial ischemia and to investigate the mechanism of ischemia-induced impairment of endothelium-dependent vasodilatation. METHODS: Yorkshire pigs underwent ameroid constrictor placement on the left circumflex coronary artery. At 3 weeks, animals were randomized to a single intrapericardial injection of saline solution (n = 10), 30 micrograms basic fibroblast growth factor (n = 10), or 2 mg basic fibroblast growth factor (n = 10). Myocardial vascular resistance in the normal (left anterior descending) and ischemic collateral-dependent (left circumflex artery) territories (using colored microspheres) and microvascular reactivity to adenosine diphosphate and sodium nitroprusside were measured before treatment and 4 weeks after treatment. The expression of inducible and endothelial nitric oxide synthase was determined in normal and ischemic myocardium by means of reverse transcriptase-polymerase chain reaction and Western analysis, and the effect of nitric oxide on endothelium-dependent vasodilatation was determined. RESULTS: Compared with results in the control group, treatment with basic fibroblast growth factor resulted in significant improvement in left circumflex artery resistance and endothelium-dependent vasodilatation, reflecting increased collaterals. Myocardial ischemia was associated with increased expression of inducible nitric oxide synthase with no change in endothelial nitric oxide synthase. However, the nitric oxide donor sodium nitroprusside did not affect endothelium-dependent vasodilatation to adenosine diphosphate. CONCLUSIONS: A single intrapericardial bolus of basic fibroblast growth factor may be a useful therapeutic strategy for the treatment of myocardial ischemia in patients with coronary artery disease. Although chronic myocardial ischemia is associated with increased expression of inducible nitric oxide synthase, it does not appear to be the cause of altered endothelial function.
Adenosine Diphosphate↗
Novel anticoagulants based on inhibition of the factor VIIa/tissue factor pathway.
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Animals↗
Collapse after oral disopyramide.
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Adult↗