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F Chiu

Publications and source records attributed to F Chiu.

7 recordsLinked to original sources
PubMed2000

Soret spectroscopic and molecular graphic analysis of human semi-beta-hemoglobin formation.

The interaction of heme-free alpha (alpha(o)) and heme-containing beta (beta(h)) chains of human hemoglobin has been monitored in 0.1 M potassium phosphate buffer, pH 7 or 8, at 5 degrees C. Soret zero and first-derivative spectra were consistent with a uniform association reaction. Stopped-flow investigations demonstrated association rates on the order of 10(7) M(-1) s(-1). This was 100-fold more rapid than the reported rate of combination of alpha(h) and beta(h) proteins. This encounter-like rate of semi-beta-hemoglobin (alpha(o)beta(h)) formation was increased by raising the pH from 7 to 8. pH change is known to affect the spatial arrangement of AB-GH helical entities. Molecular graphic analysis of modeled alpha(o) protein superimposed over native alpha(h) protein revealed an apo Mb-like structure with well-defined AB-GH segments. Repositioning of these core helical segments, resulting in increased conformational freedom of the alpha1beta1 interface, was apparently responsible for the enhanced association properties of the alpha(o) protein.

Hemoglobin A↗
PubMed2000

Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder.

In a previous study (Comings DE et al. Comparison of the role of dopamine, serotonin, and noradrenergic genes in ADHD, ODD and conduct disorder. Multivariate regression analysis of 20 genes. Clin Genet 2000: 57: 178-196) we examined the role of 20 dopamine, serotonin and norepinephrine genes in attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD), using a multivariate analysis of associations (MAA) technique. We have now brought the total number of genes examined to 42 by adding an additional 22 candidate genes. These results indicate that even with the inclusion of these additional genes the noradrenergic genes still played a greater role in ADHD than any other group. Six other neurotransmitter genes were included in the regression equation - cholinergic, nicotinic, alpha 4 receptor (CHNRA4), adenosine A2A receptor (ADOA2A), nitric oxide synthase (NOS3), NMDAR1, GRIN2B, and GABRB3. In contrast to ADHD and ODD, CD preferentially utilized hormone and neuropeptide genes These included CCK, CYP19 (aromatase cytochrome P-450), ESR1, and INS (p = 0.005). This is consistent with our prior studies indicating a role of the androgen receptor (AR) gene in a range of externalizing behavors. We propose that the MAA technique, by focusing on the additive effect of multiple genes and on the cummulative effect of functionally related groups of genes, provides a powerful approach to the dissection of the genetic basis of polygenic disorders.

Adolescent↗
PubMed1998

Fluorescence studies of human semi-beta-hemoglobin assembly.

The intrinsic fluorescence properties of human alpha apohemoglobin at protein concentrations from 1 to 5 microM in 0.1 M potassium phosphate buffer, pH 7 or 8 at 5 degrees C were monitored in the absence and presence of a fixed concentration (5 microM) of a fluorescence quenching heme-containing native or Des (146-His, 145-Tyr) beta chain partner. These "reverse quenching" studies revealed that the emission intensity changes observed correlated well with protein concentration and theoretical extent of semi-beta-hemoglobin assembly. Furthermore, the relative quenching efficiencies were calculated to be 0.32, 0.25 and 0.61 for beta (pH 7), beta (pH 8) and Des beta (pH 7) chains, respectively. Thus, heme-mediated quenching was sensitive to the expected pH induced alpha apohemoglobin conformational change and to alteration in beta chain structure. Intramolecular changes induced by carboxylterminal modification (decreased "beta chain self-quenching") appeared to enhance the intermolecular rearrangements (increased "alpha chain partner quenching") seen upon subunit assembly.

Apoproteins↗
PubMed1998

Effect of cytokines on growth of Toxoplasma gondii in murine astrocytes.

Cytokines play a significant role in the regulation of Toxoplasma gondii in the central nervous system. Cytokine-activated microglia are important host defense cells in central nervous system infections. Recent evidence indicates that astrocytes can also be activated by cytokines to inhibit intracellular pathogens. In this study, we examined the effect of gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 on the growth of T. gondii in a primary murine astrocyte culture. Pretreatment of astrocytes with IFN-gamma resulted in 65% inhibition of T. gondii growth. Neither TNF-alpha, IL-1, nor IL-6 alone had any effect on T. gondii growth. IFN-gamma in combination with either TNF-alpha, IL-1, or IL-6 caused a 75 to 80% inhibition of growth. While nitric oxide was produced by astrocytes treated with these cytokines, inhibition of T. gondii growth was not reversed by the addition of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine. Furthermore, IFN-gamma in combination with IL-1, IL-6, or TNF-alpha also induced inhibition in astrocytes derived from syngeneic mice deficient in the enzyme inducible nitric oxide synthase. This finding suggests that the mechanism of cytokine inhibition is not nitric oxide mediated. Similarly, the addition of tryptophan had no effect on inhibition, indicating that the mechanism was not mediated via induction of the enzyme indoleamine 2, 3-dioxygenase. The mechanism of inhibition remains to be elucidated. Results from this study demonstrate that cytokine-activated astrocytes are capable of significantly inhibiting the growth of T. gondii. These data indicate that astrocytes may be important host defense cells in controlling toxoplasmosis in the brain.

Animals↗
PubMed1996

Carboxyl-terminal modification influences subunit assembly of sickle hemoglobin beta chains.

The subunit assembly properties of isolated beta and Des(His-146,Tyr-145) beta chains of sickle hemoglobin were investigated by isoelectric focusing over a protein concentration range from 500-125 microM in heme. Two components (presumably tetramer and monomer) and three components (designated tetramer, dimer and monomer) were visualized for beta s and Des(His-146,Tyr-145) beta s chains, respectively. Intensitometric quantitation of Des(His-146,Tyr-145) beta s chains demonstrated a similar distribution of all three structural components before and after the addition of their heteropartner alpha chains. This is in direct contrast to the reported preferential loss of Des(His-146,Tyr-145) beta A monomer species upon assembly and points to a major role of the beta 6 residue in the overall structural homeostasis of carboxylterminal modified human beta chains.

Biopolymers↗
PubMed1990

Analysis of plasma hippurate in humans using gas chromatography-mass spectrometry: concentration and incorporation of infused [15N]glycine.

To allow in vivo determination of synthetic rates for individual proteins, physiological incorporation of infused [15N]glycine into urinary hippuric acid has been used as an indicator of intrahepatic tracer dilution. Although the kidneys might contribute to hippurate production, the relationship between hepatic, plasma, and urinary hippurate has not yet been established in humans. To further investigate these issues we developed a fast, sensitive, and reliable method for measuring simultaneously hippurate concentrations and in vivo tracer incorporation into hippurate in plasma and urine using stable isotopes and gas chromatography-mass spectrometry. We then tested this assay under several experimental conditions. Reference compounds [( 15N]- and [ring-2H5]hippurate) were synthesized and gave linear standard curves. Postabsorptive hippurate plasma levels in healthy subjects ranged from 1.2 to 10.5 microM and protein binding was 79 +/- 6% (mean +/- SD). Following a bolus dose of [15N]glycine tracer appeared in plasma hippurate; enrichment in hippurate was indistinguishable from that in glycine after an equilibration period of 20 min, indicating a close relationship between intracellular glycine and plasma hippurate. A 16-h infusion of [15N]glycine resulted in identical enrichment levels in urinary and plasma hippurate; glycine enrichment in a hepatic export protein (VLDL-ApoB) was approaching plasma hippurate but not plasma free glycine enrichment. The ability to monitor plasma hippurate is of practical advantage compared to the sampling of urine. Furthermore it allows the monitoring of rapid events in the intrahepatic dilution of an infused glycine tracer. This assay may, therefore, become an important tool in the study of hepatic protein metabolism.

Administration, Oral↗