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Biomedical subjects

L Zhang

Publications and source records attributed to L Zhang.

At least 577 records · Page 32Linked to original sources
PubMed2001

[In situ IR study of the reaction behavior of transition metal oxides-propionic acid system, Fe2Cr(mu 3-O) (mu-O2CC2H5)6(H2O)3Cl.xH2O and Cr3 (mu 3-O) (mu-O2CC2H5)6(H2O)3NO3.xH2O].

The reaction behavior of the title complexes have been investigated by means of in situ IR in nitrogen atmosphere. It has been found that they enabled the propionic acid to convert to acetaldehyde and pentanone in different temperature. The sequence of the ketonization reaction activity for metal oxides Fe3O4 > MnO2 > Cr2O3 > Co2O3 > Ni2O3 has analogy to that for metal clusters [Fe2MnOPH] > [Fe3OPH] > [Fe2CrOPH] > [Fe2CoOPH] > [Fe2NiOPH] > [Cr3OPH][OPH = (mu 3-O)(mu-O2CC2H5)6(H2O)3]. For the ketonization reactions, the reaction temperatures of transition-metal oxides were much higher than that of corresponding metal clusters [Fe2MOPH]. It has been verified that the active component of metal cluster [Fe2MOPH] is not the corresponding transition-metal oxides. The difference between Fe3O4 and Fe2O3 which catalyze the conversion of propionic acid to acetaldehyde and pentanone respectively were demonstrated.

English Abstract↗
PubMed2001

[Study on calcium-cholate-phosphate ternary complexes by FTIR spectroscopy].

The aim of this paper was to examine the calcium-cholate-phosphate tenary complexes by FTIR spectroscopy. The results indicated that the mole ratio of cholate to phosphate were 1:3 and 1:4 in ternary complexes respectively when the initial mole ratio of cholate to phosphate were 3:1 and 1.5:1 in reaction. The FTIR spectroscopic results demonstrated that in the ternary complexes Ca2+ was coordinated with O in both COO- and PO(4)3- groups.

Calcium↗
PubMed2001

[A clinical trial of oxymatrine in treating chronic viral hepatitis type B].

OBJECTIVE: To investigate the therapeutic effect of oxymatrine on chronic viral hepatitis type B. METHODS: 303 patients were randomly allocated either to a treatment group or a control group. The treatment group consisted of 253 patients treated with intravenous or intra-muscular injection of oxymatrine and oral oxymatrine capsule. Oral tiopronin was used in the control group. RESULTS: At the end of treatment, the rate of normal ALT was similar among the different groups. The rate of normal ALT was 53.3% - 58.3% in the three oxymatrine groups six months after the end of treatment. It was higher than that of the tiopronin group (P < 0.05). After a follow up of six months, the rate of negative HBeAg was 30.0% - 40.9% in the three oxymatrine groups. It was higher than that of the tiopronin group (16.7%). The rate of negative HBV DNA was 39.2% - 49.5% in the three oxymatrine groups. It was also higher than that of the tiopronin group. CONCLUSION: Oxymatrine can improve the liver function and increase the negative rate of HBeAg and HBV DNA in the patients with chronic hepatitis B. The therapeutic effect of oxymatrine will persist after the cessation of administration.

Adolescent↗
PubMed2000

A novel adapter protein employs a phosphotyrosine binding domain and exceptionally basic N-terminal domains to capture and localize an atypical protein kinase C: characterization of Caenorhabditis elegans C kinase adapter 1, a protein that avidly binds protein kinase C3.

Atypical protein kinase C isoforms (aPKCs) transmit regulatory signals to effector proteins located in the cytoplasm, nucleus, cytoskeleton, and membranes. Mechanisms by which aPKCs encounter and control effector proteins in various microenvironments are poorly understood. By using a protein interaction screen, we discovered two novel proteins that adapt a Caenorhabditis elegans aPKC (PKC3) for specialized (localized) functions; protein kinase C adapter 1 (CKA1, 593 amino acids) and CKA1S (549 amino acids) are derived from a unique mRNA by alternative utilization of two translation initiation codons. CKA1S and CKA1 are routed to the cell periphery by exceptionally basic N-terminal regions that include classical phosphorylation site domains (PSDs). Tethering of PKC3 is mediated by a segment of CKA1 that constitutes a phosphotyrosine binding (PTB) domain. Two aromatic amino acids (Phe(175) and Phe(221)) are indispensable for creation of a PKC3-binding surface and/or stabilization of CKA1.aPKC complexes. Patterns of CKA1 gene promoter activity and CKA1/CKA1S protein localization in vivo overlap with patterns established for PKC3 expression and distribution. Transfection experiments demonstrated that CKA1/CKA1S sequesters PKC3 in intact cells. Structural information in CKA1/CKA1S enables delivery of adapters to the lateral plasma membrane surface (near tight junctions) in polarized epithelial cells. Thus, a PTB domain and PSDs collaborate in a novel fashion in CKA1/CKA1S to enable tethering and targeting of PKC3. Avid ligation of a PKC isoform is a previously unappreciated function for a PTB module.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Structural properties and mechanisms that govern association of C kinase adapter 1 with protein kinase C3 and the cell periphery.

Association of an atypical protein kinase C (aPKC) with an adapter protein can affect the location, activity, substrate specificity, and physiological role of the phosphotransferase. Knowledge of mechanisms that govern formation and intracellular targeting of aPKC.adapter protein complexes is limited. Caenorhabditis elegans protein kinase C adapter proteins (CKA1 and CKA1S) bind and target aPKCs and provide prototypes for mechanistic analysis. CKA1 binds an aPKC (PKC3) via a phosphotyrosine binding (PTB) domain. A distinct, Arg/Lys-rich N-terminal region targets CKA1 to the cell periphery. We discovered that a short segment ((212)GGIDNGAFHEHEI(224)) of the V(2) (linker) region of PKC3 creates a binding surface that interacts with the PTB domain of CKA1/CKA1S. The docking domain of PKC3 differs from classical PTB ligands by the absence of Tyr and Pro. Substitution of Ile(214), Asn(216), or Phe(219) with Ala abrogates binding of PKC3 with CKA1; these residues cooperatively configure a docking site that complements an apolar surface of the CKA1 PTB domain. Phosphorylation site domains (PSD1, residues 11-25; PSD2, residues 61-77) in CKA1 route the adapter (and tethered PKC3) to the cell periphery. Phosphorylation of Ser(17) and Ser(65) in PSDs 1 and 2 elicits translocation of CKA1 from the cell surface to cytoplasm. Activities of DAG-stimulated PKCs and opposing protein Ser/Thr phosphatases can dynamically regulate the distribution of adapter protein between the cell periphery and cytoplasm.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Characterization and reconstitution of Drosophila gamma-tubulin ring complex subunits.

The gamma-tubulin ring complex (gammaTuRC) is important for microtubule nucleation from the centrosome. In addition to gamma-tubulin, the Drosophila gammaTuRC contains at least six subunits, three of which [Drosophila gamma ring proteins (Dgrips) 75/d75p, 84, and 91] have been characterized previously. Dgrips84 and 91 are present in both the small gamma-tubulin complex (gammaTuSC) and the gammaTuRC, while the remaining subunits are found only in the gammaTuRC. To study gammaTuRC assembly and function, we first reconstituted gammaTuSC using the baculovirus expression system. Using the reconstituted gammaTuSC, we showed for the first time that this subcomplex of the gammaTuRC has microtubule binding and capping activities. Next, we characterized two new gammaTuRC subunits, Dgrips128 and 163, and showed that they are centrosomal proteins. Sequence comparisons among all known gammaTuRC subunits revealed two novel sequence motifs, which we named grip motifs 1 and 2. We found that Dgrips128 and 163 can each interact with gammaTuSC. However, this interaction is insufficient for gammaTuRC assembly.

Amino Acid Motifs↗
PubMed2000

The role of Xgrip210 in gamma-tubulin ring complex assembly and centrosome recruitment.

The gamma-tubulin ring complex (gammaTuRC), purified from the cytoplasm of vertebrate and invertebrate cells, is a microtubule nucleator in vitro. Structural studies have shown that gammaTuRC is a structure shaped like a lock-washer and topped with a cap. Microtubules are thought to nucleate from the uncapped side of the gammaTuRC. Consequently, the cap structure of the gammaTuRC is distal to the base of the microtubules, giving the end of the microtubule the shape of a pointed cap. Here, we report the cloning and characterization of a new subunit of Xenopus gammaTuRC, Xgrip210. We show that Xgrip210 is a conserved centrosomal protein that is essential for the formation of gammaTuRC. Using immunogold labeling, we found that Xgrip210 is localized to the ends of microtubules nucleated by the gammaTuRC and that its localization is more distal, toward the tip of the gammaTuRC-cap structure, than that of gamma-tubulin. Immunodepletion of Xgrip210 blocks not only the assembly of the gammaTuRC, but also the recruitment of gamma-tubulin and its interacting protein, Xgrip109, to the centrosome. These results suggest that Xgrip210 is a component of the gammaTuRC cap structure that is required for the assembly of the gammaTuRC.

Amino Acid Sequence↗
PubMed2000

A quantum dot single-photon turnstile device.

Quantum communication relies on the availability of light pulses with strong quantum correlations among photons. An example of such an optical source is a single-photon pulse with a vanishing probability for detecting two or more photons. Using pulsed laser excitation of a single quantum dot, a single-photon turnstile device that generates a train of single-photon pulses was demonstrated. For a spectrally isolated quantum dot, nearly 100% of the excitation pulses lead to emission of a single photon, yielding an ideal single-photon source.

Journal Article↗
PubMed2000

Planar magnetic colloidal crystals.

We report a novel form of planar magnetic colloidal crystals formed by coated magnetic microspheres floating on a liquid meniscus. Under an external magnetic field, the balance between the repulsive magnetic interaction and the "attractive" interaction, due to the weight of the particles projected along the surface tangent, yields not only the triangular lattice with a variable lattice constant, but also all the other planar crystal symmetries such as the oblique, centered-rectangular, rectangular, and square lattices. By using two different sized magnetic particles, local formations of 2D quasi-crystallites with fivefold symmetry are also observed.

Journal Article↗
PubMed2000

Energetic and functional contribution of residues in the core binding factor beta (CBFbeta ) subunit to heterodimerization with CBFalpha.

Core-binding factors (CBFs) are a small family of heterodimeric transcription factors that play critical roles in several developmental pathways, including hematopoiesis and bone development. Mutations in CBF genes are found in leukemias and bone disorders. CBFs consist of a DNA-binding CBFalpha subunit (Runx1, Runx2, or Runx3) and a non-DNA-binding CBFbeta subunit. CBFalpha binds DNA in a sequence-specific manner, whereas CBFbeta enhances DNA binding by CBFalpha. Recent structural analyses of the DNA-binding Runt domain of CBFalpha and the CBFbeta subunit identified the heterodimerization surfaces on each subunit. Here we identify amino acids in CBFbeta that mediate binding to CBFalpha. We determine the energy contributed by each of these amino acids to heterodimerization and the importance of these residues for in vivo function. These data refine the structural analyses and further support the hypothesis that CBFbeta enhances DNA binding by inducing a conformational change in the Runt domain.

Amino Acids↗
PubMed2000

Synthesis and antitumor activity of thieno-separated tricyclic purines.

The purine ring system is undoubtedly one of the most ubiquitous heterocyclic ring systems in nature as it has the distinction of being the parent ring in countless derivatives of biological relevance. It is not surprising then that modified purines possess the potential to impact several areas, including a better understanding of the biological effects of DNA damaging agents, enzyme/substrate interactions, and in the development of more potent medicinal agents. One focus for our research at Georgia Tech has centered around the design and synthesis of a series of extended purine analogues containing a heterocyclic spacer ring, with sites set on investigations into their use as (i) potential anticancer and antiviral agents, (ii) dimensional probes for enzyme and coenzyme binding sites, and (iii) structural probes of the minor groove of DNA. The synthesis and preliminary antitumor activity of two thieno-separated purine analogues are described herein. Tricyclic 1 was synthesized in 12 steps from tribromoimidazole and with an overall yield of 7%. Tricyclic 2 was synthesized in 9 steps with an overall yield of 13%. Both 1 and 2 exhibited growth inhibitory effects on HCT116 colorectal cancer cells in vitro.

Antineoplastic Agents↗
PubMed2000

Spectrum of ST-T-wave patterns and repolarization parameters in congenital long-QT syndrome: ECG findings identify genotypes.

BACKGROUND: Congenital long-QT syndrome (LQTS) is caused by mutations of genes encoding the slow component of the delayed rectifier current (LQT1, LQT5), the rapid component of the delayed rectifier current (LQT2, LQT6), or the Na(+) current (LQT3), resulting in ST-T-wave abnormalities on the ECG. This study evaluated the spectrum of ST-T-wave patterns and repolarization parameters by genotype and determined whether genotype could be identified by ECG. METHODS AND RESULTS: ECGs of 284 gene carriers were studied to determine ST-T-wave patterns, and repolarization parameters were quantified. Genotypes were identified by individual ECG versus family-grouped ECG analysis in separate studies using ECGs of 146 gene carriers from 29 families and 233 members of 127 families undergoing molecular genotyping, respectively. Ten typical ST-T patterns (4 LQT1, 4 LQT2, and 2 LQT3) were present in 88% of LQT1 and LQT2 carriers and in 65% of LQT3 carriers. Repolarization parameters also differed by genotype. A combination of quantified repolarization parameters identified genotype with sensitivity/specificity of 85%/70% for LQT1, 83%/94% for LQT2, and 47%/63% for LQT3. Typical patterns in family-grouped ECGs best identified the genotype, being correct in 56 of 56 (21 LQT1, 33 LQT2, and 2 LQT3) families with mutation results. CONCLUSIONS: Typical ST-T-wave patterns are present in the majority of genotyped LQTS patients and can be used to identify LQT1, LQT2, and possibly LQT3 genotypes. Family-grouped ECG analysis improves genotype identification accuracy. This approach can simplify genetic screening by targeting the gene for initial study. The multiple ST-T patterns in each genotype raise questions regarding the pathophysiology and regulation of repolarization in LQTS.

Adolescent↗
PubMed2000

Enhancement of radiotherapy by hyperthermia-regulated gene therapy.

PURPOSE: Interleukin 12 (IL-12) has shown strong antitumoral effects in numerous pre-clinical studies and appears to act synergistically with radiation in murine tumors. The major impediment to its clinical use has been its systemic toxicity. While using intratumorally injected viral gene therapy vectors encoding IL-12 reduces systemic side effects substantially, elevated systemic transgene levels are still observed because adenovirus can reach the circulation. Further restricting IL-12 expression in the tumor is therefore desirable in a combined radiation and adenovirus mediated cancer gene therapy regimen. METHODS AND MATERILAS: Hyperthermia-regulated gene therapy was tested in a nonimmunogenic B16.F10 melanoma line that is syngeneic with C57BL/6 mice. For hyperthermic gene therapy, an adenoviral vector coding for IL-12 under the control of the promoter of the human heat shock protein 70B (hsp70B) was used. One week after transplantation (at a 5-7 mm diameter), tumors were irradiated with 3 x 11 Gy (mo-we-fri). Adenovirus was injected at 3 x 10(8) pfu/tumor 24 h before the last radiation fraction or 3 days afterwards. Hyperthermia was performed 24 h later at 42.5 degrees C. Growth delay to reaching 3 times initial tumor volume was chosen as the biologic endpoint. IL-12 levels in tumor and serum were determined by using the enzyme-linked immunosorbant assay (ELISA). RESULTS: Adenovirus mediated intratumoral expression of IL-12 under the control of a heat inducible promoter in combination with hyperthermia is almost as effective as that under the control of a constitutive cytomegaly virus (CMV) promoter while systemic transgene levels are substantially reduced with the heat inducible promoter. The response to radiotherapy is improved considerably when combined with heat inducible gene therapy without apparent systemic toxicity. When used as a single dose, applying IL-12 gene therapy after completion of radiotherapy appears to be beneficial. CONCLUSIONS: Hyperthermia-regulated gene therapy in combination with radiation is feasible and therapeutically effective in murine tumors with no apparent systemic toxicity.

Adenoviridae↗
PubMed2000

Characterization of the acyl carrier protein gene and the fab gene locus in Xanthomonas albilineans.

A genomic region containing the fatty acid biosynthetic (fab) genes was isolated from the sugarcane leaf-scald pathogen Xanthomonas albilineans. The order and predicted products of fabG (beta-ketoacyl reductase), acpP (acyl carrier protein), fabF (ketoacyl synthase II) and downstream genes in X. albilineans are very similar to those in Escherichia coli, with one exception. Sequence analysis, confirmed by insertional knockout and specific substrate feeding experiments, shows that the position occupied by pabC (encoding aminodeoxychorismate lyase) in other bacteria is occupied instead by pabB (encoding aminodeoxychorismate synthase component I) in X. albilineans. Downstream of pabB, X. albilineans resumes the arrangement common to characterized Gram-negative bacteria, with three transcriptionally coupled genes, encoding an ORF340 protein of undefined function, thymidylate kinase and delta' subunit of DNA polymerase III holoenzyme (HolB). Different species may obtain a common advantage from coordinated regulation of the same biosynthetic pathways using different genes in this region.

Acyl Carrier Protein↗
PubMed2000

Interaction of polyphemusin I and structural analogs with bacterial membranes, lipopolysaccharide, and lipid monolayers.

Three structural variants (PV5, PV7, and PV8) of the horseshoe crab cationic antimicrobial peptide polyphemusin I were designed with improved amphipathic profiles. Circular dichroism spectroscopy analysis indicated that in phosphate buffer polyphemusin I, PV7, and PV8 displayed the spectrum of a type II beta-turn-rich structure, but, like polyphemusin I, all three variants adopted a typical beta-sheet structure in an anionic lipid environment. Both polyphemusin I and variants were potent broad spectrum antimicrobials that were clearly bactericidal at their minimal inhibitory concentrations. The variants were moderately less active in vitro but more effective in animal models. Moreover, these variants exhibited delayed bacterial killing, whereas polyphemusin I killed Escherichia coli UB1005 within 5 min at 2.5 microg/mL. All the peptides showed similar abilities to bind to bacterial lipopolysaccharide (LPS) and permeabilize bacterial outer membranes. Consistent with this was the observation that all peptides significantly inhibited cytokine production by LPS-stimulated macrophages and penetrated polyanionic LPS monolayers to similar extents. None of the peptides had affinity for neutral lipids as evident from both tryptophan fluorescence spectroscopy and Langmuir monolayer analysis. As compared to polyphemusin I, all variants showed reduced ability to interact with anionic lipids, and the hemolytic activity of the variants was decreased by 2-4-fold. In contrast, polyphemusin I efficiently depolarized the cytoplasmic membrane of E. coli, as assessed using a membrane potential sensitive fluorescent dye 3,3-dipropylthiacarbocyanine (diSC(3)5) assay, but the variants showed a substantially delayed and decreased depolarizing ability. The coincident assessment of cell viability indicated that depolarization of the bacterial cytoplasmic membrane potential by polyphemusin I occurred prior to lethal damage to cells. Our data suggest that increase of amphipathicity of beta-sheet polyphemusin I generally resulted in variants with decreased activity for membranes. Interestingly, all variants showed an improved ability to protect mice both against infection by Pseudomonas aeruginosa and from endotoxaemia.

Animals↗
PubMed2000

A histidine residue in the catalytic mechanism distinguishes Vibrio harveyi aldehyde dehydrogenase from other members of the aldehyde dehydrogenase superfamily.

Aldehyde dehydrogenases (ALDHs) catalyze the transfer to NAD(P) of a hydride ion from a thiohemiacetal derivative of the aldehyde coupled with a cysteine residue in the active site. In Vibrio harveyi aldehyde dehydrogenase (Vh-ALDH), a histidine residue (H450) is in proximity (3.8 A) to the cysteine nucleophile (C289) and is thus capable of increasing its reactivity in sharp contrast to other ALDHs in which more distantly located glutamic acid residues are proposed to act as the general base. Mutation of H450 in Vh-ALDH to Gln and Asn resulted in loss of dehydrogenase, (thio)esterase, and acyl-CoA reductase activities; the residual activity of H450Q was higher than that of the H450N mutant in agreement with the capability of Gln but not Asn to partially replace the epsilon-imino group of H450. Coupled with a change in the rate-limiting step, these results indicate that H450 increases the reactivity of C289. Moreover, for the first time, the acylated enzyme intermediate could be directly monitored after reaction with [(3)H]tetradecanoyl-CoA showing that the H450Q mutant was acylated more rapidly than the H450N mutant. Inactivation of the wild-type enzyme with N-ethylmaleimide was much more rapid than the H450Q mutant which in turn was faster than the H450N mutant, demonstrating directly that the nucleophilicity of C289 was affected by H450. As the glutamic acid residue implicated as the general base in promoting cysteine nucleophilicity in other ALDHs is conserved in Vh-ALDH, elucidation of why a histidine residue has evolved to assist in this function in Vh-ALDH will be important to understand the mechanism of ALDHs in general, as well as help delineate the specific roles of the active site glutamic acid residues.

Acyl Coenzyme A↗
PubMed2000

Albicidin antibiotic and phytotoxin biosynthesis in Xanthomonas albilineans requires a phosphopantetheinyl transferase gene.

Xanthomonas albilineans produces a family of highly potent antibiotics and phytotoxins called albicidins, which are key pathogenesis factors in the systemic development of leaf scald disease of sugarcane. A gene (xabA) required for albicidin biosynthesis encodes a peptide of 278 amino acids, including the signature sequence motifs for phosphopantetheinyl transferases (PPTases) that activate polyketide and non-ribosomal peptide synthetases. The Escherichia coli entD gene, which encodes a PPTase involved in biosynthesis of enterobactin (a siderophore), restored biosynthesis of albicidin (a DNA replication inhibitor) in X. albilineans Tox- LS156 (xabA::Tn5). We conclude that XabA is a PPTase required for post-translational activation of synthetases in the albicidin biosynthetic pathway. This is the first antibiotic or toxin biosynthesis gene characterized from the genus Xanthomonas, and the first demonstration that antibiotic synthetases in the Pseudomonadaceae, like those in the Enterobacteriaceae and in Gram-positive bacteria, can require activation by a PPTase. Coupled with the recent demonstration of a separate albicidin biosynthetic gene cluster, the results indicate the possibility for overproduction of albicidins,which allows better understanding and application of these potent inhibitors of prokaryote DNA replication.

Amino Acid Sequence↗