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Biomedical subjects

H Huang

Publications and source records attributed to H Huang.

At least 55 records · Page 3Linked to original sources
PubMed2004

Oxidant stress in kidneys of spontaneously hypertensive rats involves both oxidase overexpression and loss of extracellular superoxide dismutase.

Oxidant stress is an important contributor to renal dysfunction and hypertension. We have previously demonstrated that regulation of renal oxygen consumption by nitric oxide (NO) is impaired in the kidney of spontaneously hypertensive rats (SHR) due to increased superoxide production. We further explored the mechanisms of enhanced oxidant stress in the kidney of SHR. Suppression of cortical oxygen consumption by bradykinin (BK) or enalaprilat (Enal), which act through stimulation of endogenous NO, was impaired in SHR (BK: -14.1 +/- 1.2%; Enal: -15.5 +/- 1.2%) and was restored by addition of apocynin, an inhibitor of assembly of the NAD(P)H oxidase complex (BK: -21.0 +/- 0.6%; Enal: -25.3 +/- 1.4%), suggesting this as the source of enhanced superoxide production. Addition of an angiotensin type 1 receptor blocker, losartan, also restored responsiveness to control levels (BK: -22.0 +/- 1.1%; Enal: -23.6 +/- 1.3%), suggesting that ANG II is responsible for enhanced oxidase activity. A similar defect in responsiveness to BK and Enal could be induced in Wistar-Kyoto kidneys by ANG II and was reversed by a superoxide scavenger (tempol), apocynin or losartan. Immunoblotting of cortical samples demonstrated enhanced expression of endothelial NO synthase (eNOS 1.9x) and NAD(P)H oxidase components (gp91(phox) 1.6x and Rac-1 4.5x). Expression of SOD-1 and -2 were unchanged, but SOD-3 was significantly decreased in SHR (0.5x). Thus NO bioavailability is impaired in SHR owing to an ANG II-mediated increase in superoxide production in association with enhanced expression of NAD(P)H oxidase components, despite increased expression of eNOS. Loss of SOD-3, an important superoxide scavenger, may also contribute to enhanced oxidant stress.

Acetophenones↗
PubMed2004

Step and ramp induction of myocardial ischemia: comparison of in vivo and in silico results.

This study tested the robustness of our computational model of myocardial metabolism by comparing responses to two different inputs with experimental data obtained in pigs under similar conditions. Accordingly, an abrupt and a gradual reduction in coronary flow of similar magnitude were implemented and used as model input. After flow reductions reached 60% from control values, ischemia was kept constant for 60 min in both groups. Our hypotheses were that: (1) these two flow-reduction profiles would result in different transients (concentrations and flux rates) while having similar steady-state values and (2) our model-simulated responses would predict the experimental results in an anesthetized swine model of myocardial ischemia. The two different ischemia-induction patterns resulted in the same decrease in steady-state MVO2 and in similar steady-state values for metabolite concentrations and flux rates at 60 min of ischemia. While both the simulated and experimental results showed decreased glycogen concentration, accumulation of lactate, and net lactate release with ischemia, the onset of glycogen depletion and the switch to lactate efflux were more rapid in the experiments than in the simulations. This study demonstrates the utility of computer models for predicting experimental outcomes in studies of metabolic regulation under physiological and pathological conditions.

Animals↗
PubMed2003

Characterization of gaseous and solid product from thermal plasma pyrolysis of waste rubber.

Pyrolysis of waste rubber in thermal plasma is studied for the purpose of producing gaseous fuel and recovering carbon black filler. The plasma reactor has a dc arc nitrogen plasma generator with a maximum electric power input of 62.5 kVA and a reaction chamber of 50 mm inner diameter and 1000 mm height. The results of a series of experiments have shown that the main components of the gaseous product are H2, CO, C2H2, CH4, and C2H4; the heat value of the gas is about 5-9 MJ/Nm3. The solid product contains more than 80 wt % elemental carbon, has a surface area of about 65 m2/g, and is referred to as pyrolytic carbon black (CBp). X-ray photoelectron spectroscopy (XPS) analysis has revealed that the CBp has mainly graphitic carbon structure similar to those of commercial carbon black. The CBp may be used as semireinforcing carbon black in nontire rubber applications, or, after upgrading, as carbon black filler for tire. Thus thermal plasma pyrolysis is potentially a useful way of treating waste rubber for resource recovery.

Air Pollutants↗
PubMed2003

Observation of higher-order snake resonances in polarized proton acceleration in RHIC.

Higher-order and coupled snake resonances were observed during the 2002 polarized proton run in RHIC. Strong depolarization was observed when the fractional part of the vertical betatron tune approached 1/4, and when the fractional part of the horizontal tune approached 3/14. Because of the closed orbit error, each snake resonance splits into two. From the width of the observed snake resonances, we can derive the strength of the imperfection spin resonance. Our results appear consistent with the measured closed orbit error.

Journal Article↗
PubMed2003

ATP augments peptide release from rat sensory neurons in culture through activation of P2Y receptors.

ATP has recently emerged as an important proinflammatory mediator that has direct excitatory actions on sensory neurons through activation of ion channel-coupled P2X receptors. The purpose of the current work is to assess whether ATP alters the release of neuropeptides from sensory neurons and the receptors mediating this putative action. Exposing embryonic sensory neurons in culture to concentrations of ATP up to 300 microm did not increase the release of immunoreactive substance P or calcitonin gene-related peptide from sensory neurons. However, pre-exposing sensory neurons to 0.1 to 100 microm ATP prior to and throughout administration of 30 nM capsaicin resulted in a significant augmentation of release evoked by the vanilloid. This sensitizing action of ATP is blocked by suramin but not pyridoxal phosphate-6-azobenzene-2,4-disulfonic acid and is mimicked by the P2Y receptor agonists, 2-2-chloroadenosine triphosphate and UTP, but not by 2-(methylthio)adenosine 5'-triphosphate or alpha,beta-methyleneadenosine 5'-diphosphate. This profile of drug actions suggests that the sensitizing actions of ATP are mediated by P2Y receptors. Pretreating sensory neurons with bisindolylmaleimide I, a selective protein kinase C (PKC) inhibitor, attenuates the augmentation of capsaicin-induced peptide release by ATP, further implicating P2Y receptors in the actions of ATP. Immunoblotting also indicates the presence of P2Y2-like immunoreactive substance in embryonic dorsal root ganglia neurons. Together, these data support the notion that ATP acts at P2Y receptors in sensory neurons in a PKC-dependent manner to augment their sensitivity to other stimuli.

Adenosine Triphosphate↗
PubMed2003

Measurements of the Decay KL-->e+ e- mu+ mu-.

The KTeV experiment at Fermilab has isolated a total of 132 events from the rare decay K(L)-->e+ e- mu+ mu-, with an estimated background of 0.8 events. The branching ratio of this mode is determined to be [2.69+/-0.24(stat)+/-0.12(syst)]x10(-9), with a radiative cutoff of M(2)(ee mu mu)/M(2)(K)>0.95. The first measurement using this mode of the parameter alpha from the D'Ambrosio-Isidori-Portolès (DIP) model of the K(L)gamma*gamma* vertex yields a result of -1.59+/-0.37, consistent with values obtained from other decay modes. Because of the limited statistics, no sensitivity is found to the DIP parameter beta. We use this decay mode to set limits on CP and lepton violation.

Journal Article↗
PubMed2003

Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice.

Glucagon, the counter-regulatory hormone to insulin, is secreted from pancreatic alpha cells in response to low blood glucose. To examine the role of glucagon in glucose homeostasis, mice were generated with a null mutation of the glucagon receptor (Gcgr(-/-)). These mice display lower blood glucose levels throughout the day and improved glucose tolerance but similar insulin levels compared with control animals. Gcgr(-/-) mice displayed supraphysiological glucagon levels associated with postnatal enlargement of the pancreas and hyperplasia of islets due predominantly to alpha cell, and to a lesser extent, delta cell proliferation. In addition, increased proglucagon expression and processing resulted in increased pancreatic glucogen-like peptide 1 (GLP-1) (1-37) and GLP-1 amide (1-36 amide) content and a 3- to 10-fold increase in circulating GLP-1 amide. Gcgr(-/-) mice also displayed reduced adiposity and leptin levels but normal body weight, food intake, and energy expenditure. These data indicate that glucagon is essential for maintenance of normal glycemia and postnatal regulation of islet and alpha and delta cell numbers. Furthermore, the lean phenotype of Gcgr(-/-) mice suggests glucagon action may be involved in the regulation of whole body composition.

Animals↗
PubMed2003

Inactivation kinetics of mushroom tyrosinase in the dimethyl sulfoxide solution.

Mushroom tyrosinase (EC 1.14.18.1) is a kind of copper-containing oxidase that catalyzes both the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones and then forms brown or black pigments. In the present paper, the effects of dimethyl sulfoxide on the enzyme activity for the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) have been studied. The results show that low concentrations of dimethyl sulfoxide (DMSO) can lead to reversible inactivation of the enzyme, and the IC(50) is estimated to be 2.45 M. Inactivation of the enzyme by DMSO is classified as mixed type. The kinetics of inactivation of mushroom tyrosinase at low concentrations of DMSO solution has been studied using the kinetic method of the substrate reaction. The rate constants of inactivation have been determined. The results show the free enzyme molecule is more fragile than the enzyme-substrate complex in the DMSO solution. It is suggested that the presence of the substrate offers marked protection of this enzyme against inactivation by DMSO.

Agaricales↗
PubMed2003

Intercontinental genetic divergence of Castanea species in eastern Asia and eastern North America.

Castanea is one of the many plant genera with a disjunct distribution pattern between eastern Asia and eastern North America. Five species from three sections of the genus were investigated to examine genetic divergence between eastern Asian and eastern North American species. A total of 62 native populations were sampled for allelic variation at isozyme loci. The Chinese chestnut C. mollissima had the highest genetic variability, while the American C. dentata had the lowest genetic variability. The highest intracontinental genetic identities were observed between the Allegheny and Ozark chinkapins (0.931) and between C. mollissima and C. seguinii (0.870), while lower identities were detected between the American C. pumila and C. dentata (0.720-0.729). In intercontinental comparisons, genetic identities of 0.505, 0.495 and 0.507 were observed between the American chestnut and the Chinese C. mollissima, C. seguinii and C. henryi, respectively, whereas the Ozark chinkapin C. pumila var. ozarkensis had lower identities of 0.469, and 0.435 with C. mollissima and C. seguinii, respectively, but a slightly higher identity of 0.520 with C. henryi, the Chinese chinkapin. Divergence times were estimated at 10-13 million years before present between C. dentata and C. mollissima, and C. pumila var. ozarkensis and C. henryi.

Biological Evolution↗
PubMed2003

The tuberous sclerosis complex (TSC) pathway and mechanism of size control.

We have identified three groups of growth-constraint genes using mosaic genetic screens in Drosophila melanogaster, including PTEN (phosphatase and tensin homologue deleted on chromosome 10), and the tuberous sclerosis complex (TSC) genes, Tsc1 and Tsc2. Our studies show that all three groups of genes participate in mechanisms that regulate organ and organism size in animals. We propose that mechanisms of organ size control are critical targets for diseases, such as tumorigenesis, which require an increase in tissue size and total mass, and for evolutionary events that alter the size of organisms. Using genetic and biochemical methods, we have shown that Tsc1 and Tsc2 function in the insulin/phosphoinositide 3-kinase (PI3K)/Akt pathway. We have shown that Akt regulates the Tsc1-Tsc2 complex by directly phosphorylating Tsc2. We have shown further that S6 kinase (S6K) is a downstream component of the PI3K/Akt/TSC pathway and reduction of S6K activity can block TSC defects. Recent studies from many laboratories have now confirmed our findings in mice, rats and human patients, and have shown that drugs that antagonize S6K activities, such as rapamycin, diminish tumours in TSC-deficient mice and rats. Clinical trials based on these findings have begun. Given that other components of the pathway, such as PTEN, are also mutated in a large number of cancer patients and that these components regulate intracellular insulin signalling, therapeutics based on the knowledge of the pathway could have effects beyond the TSC patient population.

Animals↗
PubMed2003

On the sensitivity of wall stresses in diseased arteries to variable material properties.

Accurate estimates of stress in an atherosclerotic lesion require knowledge of the material properties of its components (e.g., normal wall, fibrous plaque, calcified regions, lipid pools) that can only be approximated. This leads to considerable uncertainty in these computational predictions. A study was conducted to test the sensitivity of predicted levels of stress and strain to the parameter values of plaque used in finite element analysis. Results show that the stresses within the arterial wall, fibrous plaque, calcified plaque, and lipid pool have low sensitivities for variation in the elastic modulus. Even a +/- 50% variation in elastic modulus leads to less than a 10% change in stress at the site of rupture. Sensitivity to variations in elastic modulus is comparable between isotropic nonlinear, isotropic nonlinear with residual strains, and transversely isotropic linear models. Therefore, stress analysis may be used with confidence that uncertainty in the material properties generates relatively small errors in the prediction of wall stresses. Either isotropic nonlinear or anisotropic linear models provide useful estimates, however the predictions in regions of stress concentration (e.g., the site of rupture) are somewhat more sensitive to the specific model used, increasing by up to 30% from the isotropic nonlinear to orthotropic model in the present example. Changes resulting from the introduction of residual stresses are much smaller.

Anisotropy↗
PubMed2003

Ultrasonic absorption in aqueous solutions of amino acids at neutral pH.

Ultrasonic absorption coefficients in aqueous solutions of glycine, L-alanine, imidazole, L-phenylalanine, L-histidine and L-tryptophan at neutral pH were measured in the range from 0.8 to 220 MHz at 25 degrees C. A characteristic ultrasonic relaxation phenomenon was observed only in the solution of L-histidine with a relaxation frequency at around 2 MHz at neutral pH. It was proposed from the concentration independent relaxation frequency and the linear concentration dependence of the maximum absorption per wavelength that the relaxation mechanism was associated with a perturbation of the rotational isomeric equilibrium of the L-histidine molecule. The existence of two rotational isomeric forms of L-histidine in water was examined by semiempirical quantum chemical methods, in order to determine the free energy difference between the two states. The forward and backward rate constants were determined from the relaxation frequency and the energy change. Also, the standard volume change of the reaction was estimated from the concentration dependence of the maximum absorption per wavelength. It was speculated that L-histidine fulfills a specific function among amino acids because of the rotational motion in the molecule, in addition to its well-established acid-base properties.

Absorption↗
PubMed2003

The Dentin matrix protein 1 (Dmp1) is specifically expressed in mineralized, but not soft, tissues during development.

Dentin Matrix Protein 1 (Dmp1) was originally identified from dentin. However, its expression and function in vivo are not clear. To clarify these two issues, we have generated mice carrying a truncated Dmp1 gene by using gene targeting to replace exon 6 with a lacZ gene. Northern blot analysis shows the expected 5.8-kb Dmp1-lacZ fusion transcript and loss of the wild-type 2.8-kb Dmp1 transcript, confirmed by a lack of immunostaining for the protein. Using heterozygous animals, we demonstrate that Dmp1 is specific for mineralized tissues. Not previously shown, Dmp1 is also expressed in pulp cells. Dmp1-deficient embryos and newborns display no apparent gross abnormal phenotype, although there are a modest expansion of the hypertrophic chondrocyte zone and a modest increase in the long bone diameter. This suggests that DMP1 is not essential for early mouse skeletal or dental development.

Animals↗
PubMed2003

The role of PTEN in the progression and survival of prostate cancer.

PTEN (phosphatase and tensin homologue deleted on chromosome-10), a dual specificity phosphatase, is a tumor suppressor gene whose inactivation has been associated with many different types of cancer including prostate cancer. Prostate adenocarcinoma is one of the most commonly diagnosed malignancies afflicting the male population in both the United States and Europe. The frequency of PTEN inactivation appears to increase during the progression of prostatic cancer. The physical loss of the PTEN genetic locus in prostate cancer progression has been well characterized, however the molecular implication of this loss of PTEN remains enigmatic. The purpose of this review is to describe the functional role of PTEN in the molecular pathogenesis of prostatic disease. We review the function of PTEN discussing its association with the phosphoinositol 3-kinase (PI3K) and mitogen activated protein kinase (MAPK) signal transduction pathways. Additionally, we discuss the role of PTEN in the regulation of apoptotic pathways involving the anti-apoptotic gene bcl-2 and the pro-apoptotic ligand TRAIL. We also review the mechanisms that can lead to the loss of PTEN function. We describe genetic inactivation including loss of heterozygosity, haploinsufficiency and mutation. We conclude by outlining epigenetic loss including methylation, post-translational modifications and oxidative stress.

Gene Silencing↗
PubMed2002

Measurement of analyzing power for proton-carbon elastic scattering in the coulomb-nuclear interference region with a 22-GeV/c polarized proton beam.

The analyzing power for proton-carbon elastic scattering in the Coulomb-nuclear interference region of momentum transfer, 9.0x10(-3)<-t<4.1x10(-2) (GeV/c)(2), was measured with a 21.7 GeV/c polarized proton beam at the Alternating Gradient Synchrotron of Brookhaven National Laboratory. The ratio of hadronic spin-flip to nonflip amplitude, r(5), was obtained from the analyzing power to be Rer(5)=0.088+/-0.058 and Imr(5)=-0.161+/-0.226.

Journal Article↗
PubMed2002

Sterol carrier protein-2: structure reveals function.

The multiple actions of sterol carrier protein-2 (SCP-2) in intracellular lipid circulation and metabolism originate from its gene and protein structure. The SCP-x/pro-SCP-2 gene is a fusion gene with separate initiation sites coding for 15-kDa pro-SCP-2 (no enzyme activity) and 58-kDa SCP-x (a 3-ketoacyl CoA thiolase). Both proteins share identical cDNA and amino acid sequences for 13-kDa SCP-2 at their C-termini. Cellular 13-kDa SCP-2 derives from complete, posttranslational cleavage of the 15-kDa pro-SCP-2 and from partial posttranslational cleavage of 58-kDa SCP-x. Putative physiological functions of SCP-2 have been proposed on the basis of enhancement of intermembrane lipid transfer (e.g., cholesterol, phospholipid) and activation of enzymes involved in fatty acyl CoA transacylation (cholesterol esters, phosphatidic acid) in vitro, in transfected cells, and in genetically manipulated animals. At least four important SCP-2 structural domains have been identified and related to specific functions. First, the 46-kDa N-terminal presequence present in 58-kDa SCP-x is a 3-ketoacyl-CoA thiolase specific for branched-chain acyl CoAs. Second, the N-terminal 20 amino acid presequence in 15-kDa pro-SCP-2 dramatically modulates the secondary and tertiary structure of SCP-2 as well as potentiating its intracellular targeting coded by the C-terminal peroxisomal targeting sequence. Third, the N-terminal 32 amino acids form an amphipathic a-helical region, one face of which represents a membrane-binding domain. Positively charged amino acid residues in one face of the amphipathic helices allow SCP-2 to bind to membrane surfaces containing anionic phospholipids. Fourth, the hydrophobic faces of the N-terminal amphipathic a helices along with beta strands 4, 5, and helix D form a ligand-binding cavity able to accommodate multiple types of lipids (e. g., fatty acids, fatty acyl CoAs, cholesterol, phospholipids, isoprenoids). Two-dimensional 1H-15N heteronuclear single quantum coherence spectra of both apo-SCP-2 and of the 1:1 oleate-SCP-2 complex, obtained at pH 6.7, demonstrated the homogenous formation of holo-SCP-2. While comparison of the apo- and holoprotein amide fingerprints revealed about 60% of the resonances remaining essentially unchanged, 12 assigned amide residues underwent significant chemical-shift changes upon oleic acid binding. These residues were localized in three regions: the juncture of helices A and B, the mid-section of the beta sheet, and the interface formed by the region of beta strands 4, 5, and helix D. Circular dichroism also showed that these chemical-shift changes, upon oleic acid binding, did not alter the secondary structure of SCP-2. The nuclear magnetic resonance chemical shift difference data, along with mapping of the nearby hydrophobic residues, showed the oleic acid-binding site to be comprised of a pocket created by the face of the beta sheet, helices A and B on one end, and residues associated with beta strands 4, 5, and helix D at the other end of the binding cavity. Furthermore, the hydrophobic nature of the previously ill-defined C-terminus suggested that these 20 amino acids may form a 'hydrophobic cap' which closes around the oleic acid upon binding. Thus, understanding the structural domains of the SCP-x/pro-SCP-2 gene and its respective posttranslationally processed proteins has provided new insights into their functions in intracellular targeting and metabolism of lipids.

Acetyl-CoA C-Acetyltransferase↗