Activation of a terminal carboxylic acid by an internal oxazole: a novel synthesis of macrocyclodepsipeptide.
Explore the source record for details and available documents.
Carboxylic Acids↗
Biomedical subjects
G Zhao
Publications and source records attributed to G Zhao.
An eukaryotic-type serine/threonine protein kinase involved in the carbon source-dependent pigment biosynthesis in Amycolatopsis mediterranei U32.
The structural gene, pkmA, was cloned and sequenced from a rifamycin SV-producing Amycolatopsis mediterranei U32 strain. The N-terminal portion of the deduced amino acid sequence of pkmA showed significant similarity to the family of serine/threonine protein kinases. It contains all the structural features which are highly conserved in protein kinases, including the Gly-X-Gly-X-X-Gly motif of ATP binding and the essential amino acids known to be important for the recognition of the correct hydroxyamino acid in serine/threonine protein specific kinases. The protein possesses a region rich in Ala and Pro residues around the middle of pkmA open reading frame, which might be involved in the transmembrane function, as suggested by PhoA fusion protein analysis. The pkmA gene was expressed in Escherichia coli as a glutathione S-transferase (GST) fusion protein, and the protein was found to have the activity of autophosphorylation. A double crossover gene replacement was achieved by inserting an aparmycin resistance gene into pkmA in A. mediterranei chromosomal DNA. The phenotypic analysis of the mutant suggested that pkmA gene is involved in carbon source-dependent pigment formation in A. mediterranei U32.
Alkaline Phosphatase↗
A new locus for hereditary gingival fibromatosis (GINGF2) maps to 5q13-q22.
Gingival fibromatosis (GINGF) is an oral disorder characterized by enlargement of the gingiva. It occurs either as the sole phenotype or combined with other symptoms. Thus far, one GINGF locus has been mapped on chromosome 2, at 2p21, and a second possible locus has been mapped to 2p13. However, the genes responsible for this disorder have not been elucidated. We identified a four-generation Chinese GINGF family in which the disease manifests within 1 year after birth. After exclusion of the two known GINGF loci in this family, we performed a genome-wide search to map the chromosome location of the responsible gene. We identified a new locus, GINGF2, on chromosome 5q13-q22 with a maximum two-point lod score of 4.31 at D5S1721 (theta = 0.00). Haplotype analysis placed the critical region in the interval defined by D5S1491 and D5S1453. Within this region, calcium/calmodulin-dependent protein kinase IV (CAMK4) is a strong candidate.
Age of Onset↗
[Keratin 17 gene mutation in patients with steatocystoma multiplex].
OBJECTIVE: To study the relationship between steatocystoma multiplex (SCM) and keratin 17 gene mutation. METHODS: The keratin 17 gene mutation in the cDNA of cystic tissue of 5 patients of SCM and in the DNA in peripheral blood of 25 patients with SCM from a SCM family was studied by direct sequencing of the RT-PCR products, nested PCR, and restricted fraction length polymorphism (RFLP) analysis. Thirty-nine blood specimens from the unaffected members of that family were collected and tested too. Ten DNA pool specimens and other 2000 DNA pool specimens of normal individuals outside that SCM family were used as controls. RESULTS: In the base 428, 94(th) codon in keratin 17 gene in the cDNA of patients' cystic tissue, R94C mutation, a G-->A mutation, was detected Nested PCR, and restricted enzyme Acil polymorphism analysis showed that in the DNA specimens of peripheral blood of patients a mutated allele lacking enzyme cutting locus was detected, thus causing an uncut band with 200 bp while the corresponding allele was cut and caused two bands with 108 bp and 92 bp. In the DNA pool specimens of normal controls only these two bands with 108 bp and 92 bp were observed. CONCLUSION: The R94C mutation in keratin 17 gene is one of the genetic bases of SCM in Chinese. The results of this study provide scientific data for genetic diagnosis and counseling of SCM.
Adolescent↗
A novel multicomponent synthesis of polysubstituted 5-aminooxazole and its new scaffold-generating reaction to pyrrolo[3,4-b]pyridine.
A novel three-component synthesis of 5-amino oxazole (1) is reported. Its subsequent reaction with alpha,beta-unsaturated acyl chloride leads to polysubstituted pyrrolopyridine (2). A triple domino process, acylation/IMDA/retro-Michael cycloreversion, was involved in the latter process. The methodology allows the quick preparation, from simple and readily available inputs, of highly functionalized title compounds not easily accessed by other methods.
Journal Article↗
The effects of inhalation exposure to bromo-dichloromethane on specific rat CYP isoenzymes.
Several cytochrome P450 (CYP) isoenzymes may be involved in the metabolism of bromo-dichloromethane (BDCM), a drinking water disinfection byproduct. After 4-h inhalation exposures of male F344 rats to BDCM between 100 and 3200 p.p.m., hepatic microsomal methoxyresorufin demethylase (MROD), ethoxyresorufin de-ethylease (EROD) and pentoxyresorufin dealkylase (PROD) activities showed modest increases at low exposure levels and larger decreases at high exposure levels, compared with controls. Western blots for CYP1A2 and CYP2B1 showed similar trends. In addition, p-nitrophenol hydroxylase (PNP) activity was measured and Western blots for CYP2E1 were performed. CYP2E1 and CYP2B1 isoenzymes are known to metabolize BDCM (Thornton-Manning, J.R., Gao, P., Lilly, P.D., Pegram, R.A., 1993. Acute bromodichloromethane toxicity in rats pretreated with cytochrome P450 inducers and inhibitors. The Toxicologist 13: 361). When compared with a multiple gavage study of BDCM in female F344 rats (Thornton-Manning, J.R., et al., 1994. Toxicology 94, 3-18), the results of the two studies for EROD, PROD, and PNP activities were qualitatively the same; PNP activity did not change, while both PROD and EROD activities decreased at high exposures. In the current work, Western blots for CYP2E1, CYP2B1 and CYP1A2 supported the results from the PNP, PROD and MROD activities, respectively. The decreases in MROD and PROD activities and in Western blots for CYP1A2 and CYP2B1 at high exposures suggest that BDCM may be a suicide substrate for these CYP isoenzymes. Other important conclusions that can be drawn from the comparison between the current and prior work are that the liver response is similar for both sexes, and it is also similar for inhalation and gavage exposures under these conditions. Finally, the decrease in EROD activity at high doses, found in both studies, may be a further reflection of CYP1A2 activity, since little or no CYP1A1 activity is normally found in uninduced rat liver and CYP1A2 is known to metabolize ethoxyresorufin, although much more slowly than CYP1A1.
Administration, Inhalation↗
Tissue plasminogen activator protects hippocampal neurons from oxygen-glucose deprivation injury.
We have previously shown that tissue plasminogen activator (tPA) participates in the neurotoxicity of microglial conditioned medium (MgCM). Killing of hippocampal neurons by MgCM was prevented by both plasminogen activator inhibitor-1 (PAI-1) and anti-tPA antibody. An N-methyl-D-aspartate (NMDA) receptor blocker protected neurons from MgCM, suggesting that this subtype of glutamate receptor is involved. Whereas glutamate receptor-mediated events are important in cerebral ischemia and tPA has previously been shown to enhance excitotoxicity in hippocampus, we hypothesized that tPA would exaggerate oxygen glucose deprivation (OGD) injury in cultures of hippocampal neurons. Dissociated rat hippocampal cells were grown under conditions designed to optimize neuronal growth while minimizing glial replication. At 7--10 days, cultures were subjected to OGD for 2.5 hr. Recombinant human tPA (1,000 IU) was added immediately after OGD. Viability was assessed 24 hr later. Viable, apoptotic, and necrotic cells were classified and quantified based on staining patterns of acridine orange and ethidium bromide under fluorescence microscopy. tPA alone did not alter neuronal integrity. OGD produced significant neuronal death (viability reduced by 45%, P < 0.001). tPA completely protected OGD-exposed cultures. Potential mechanisms of tPA protection were explored. Whereas tPA antibody abolished the protective effect of tPA, its proteolytic inhibitor PAI-1 did not alter the effect. The effect of tPA was tested in separate free radical and excitatory amino acid insults. It did not protect neurons from hydrogen peroxide (1 microM), S-nitro-acetylpenicillamine (10 microM), glutamate (50 microM), or NMDA (10 microM) damage but significantly attenuated injury caused by 250 microM kainate. We conclude that tPA is capable of protecting hippocampal neurons from OGD by a nonproteolytic action. The mechanism of protection was not defined, although attenuation of AMPA/kainate glutamate receptors may play a role.
Animals↗
Determination of double decker sandwich structured La-substituted chlorophyll a by EXAFS.
As a representative natural porphyrin derivative, it is interesting to know the chemical form of lanthanide in chlorophyll a. We select the natural fern dicranopteris dichotoma, the most lanthanide-concentrated plant known, to isolate the chlorophyll a for our study. It is found by EXAFS that lanthanum substitutes in the magnesium position in chlorophyll and coordinates with the porphyrin ring. The lanthanum is seen to have a similar coordination structure to a sandwich-type lanthanide complex, with the La surrounded by eight nitrogen atoms from two porphyrin rings with average La-N bond length of 2.65 A.
Chlorophyll↗
Selective fowler reductions: asymmetric total syntheses of isofagomine and other 1-azasugars from methyl nicotinate.
[figure: see text] An efficient, high-yielding strategy has been developed for the asymmetric synthesis of 1-N-iminosugars (1-azasugars), a new class of glycosidase inhibitors with promising biomedical applications. A highly regioselective procedure for the 1,2-reduction of substituted pyridines was employed to transform methyl nicotinate into several representative 1-azasugars.
Aza Compounds↗
Both gamma delta T cells and NK cells inhibit the engraftment of xenogeneic rat bone marrow cells and the induction of xenograft tolerance in mice.
In murine allogeneic bone marrow transplantation recipients, treatment of the hosts with a nonmyeloablative regimen, including depleting anti-CD4 and anti-CD8 mAbs, allows establishment of long-term mixed chimerism and donor-specific tolerance. However, in the xenogeneic rat-to-mouse combination, additional anti-Thy1.2 and anti-NK1.1 mAbs are required. We have now attempted to identify the xenoresistant mouse cell populations that are targeted by anti-NK1.1 and anti-Thy1.2 mAbs. C57BL/6 (B6) wild-type, B6 TCRbeta(-/-), and B6 TCRdelta(-/-) mice received anti-CD4 and anti-CD8 mAbs, followed by 3 Gy of whole body irradiation, 7 Gy of thymic irradiation, and transplantation of T cell-depleted rat bone marrow cells. Anti-NK1.1 and anti-Thy1.2 mAbs were additionally administered to some groups. Increased rat chimerism was observed in TCRdelta(-/-) mice treated with anti-CD4, anti-CD8, and anti-NK1.1 mAbs compared with similarly treated TCRbeta(-/-) mice. In TCRbeta(-/-) mice, but not in TCR delta(-/-) mice, donor chimerism was increased by treatment with anti-Thy1.2 mAb, indicating that CD4(-)CD8(-)TCRgammadelta(+)Thy1. 2(+)NK1.1(-) cells (gammadelta T cells) are involved in the rejection of rat marrow. In addition, chimerism was enhanced in both TCRbeta(-/-) and TCRdelta(-/-) mice treated with anti-CD4, anti-CD8, and anti-Thy1.2 mAbs by the addition of anti-NK1.1 mAb to the conditioning regimen. Donor-specific skin graft prolongation was enhanced by anti-Thy1.2 and anti-NK1.1 mAbs in TCRdelta(-/-) mice. Therefore, in addition to CD4 and CD8 T cells, gammadelta T cells and NK cells play a role in resisting engraftment of rat marrow and the induction of xenograft tolerance in mice.
Animals↗
Asymmetric borane reduction of prochiral ketones by polymer-supported chiral sulfonamides.
Explore the source record for details and available documents.
Journal Article↗
Fluorescent Bocillins: synthesis and application in the detection of penicillin-binding proteins.
Novel fluorescent analogs of penicillin V were synthesized and evaluated for efficacy in the detection of penicillin binding proteins (PBPs). These molecules include the full structure of penicillin V, with the potent Bodipy fluorophore attached to the para-position of the penicillin V phenyl group. The green fluorescent Bocillin FL and the near-infrared (IR) fluorescent Bocillin 650/665 probes were shown to bind to PBPs, both purified and from membrane preparations, with high affinity and specificity. These reagents allow for facile detection of 2-4 ng of purified PBP with the aid of a fluorescent scanner.
Bacteria↗
Diet and drug therapy: a dynamic duo for reducing coronary heart disease risk.
A large proportion of the United States population requires aggressive low-density lipoprotein (LDL) cholesterol- lowering therapy to meet the new treatment guidelines established by the National Cholesterol Education Program Adult Treatment Panel III. This has further widened the gap between the number of people being treated compared with those who should be treated. Moreover, many people being treated do not meet their LDL cholesterol goal. Diet and healthy lifestyle practices remain the cornerstone of treatment to lower LDL cholesterol. Pharmacologic therapy has assumed an increasingly important role in reaching LDL cholesterol goals. Diet and healthy-lifestyle interventions have been shown to augment the benefits of cholesterol-lowering drugs. Together, this dynamic duo provides the most effective clinical means identified to date for maximally lowering LDL cholesterol levels.
Anticholesteremic Agents↗
Rare earth elements in naturally grown fern Dicranopteris linearis in relation to their variation in soils in south-Jiangxi region (southern China).
Ferns (Dicranopteris linearis) and soils, sampled from four rare earth mining areas and one non-mining area locating in South-Jiangxi region, were chosen for analysis of 15 rare earth elements (REEs) by inductively coupled plasma-mass spectrometry (ICP-MS). The fern samples were divided into 4 parts: root, stem, petiole, and lamina. The soils of the same sites were also sampled, and 4 soil layers were observed at the profile: A (0-20 cm depth), B (20-150 cm depth), C (150-400 cm depth), and D (rock). The distribution patterns and transportation characteristics of REEs of different soil layers and of different parts of D. linearis were studied. The results showed that in the soil layers, the sigma REE (the sum of the concentrations of 15 REEs) of A layer, as well as B layer were lower than that of C layer, but Ce was relatively concentrated in A layer. The sigma REE of different parts of D. linearis were lamina, root > stem > petiole. The REE distribution patterns of D. linearis root were similar to the total REE distribution patterns of the A layer of their host soils, especially to the soluble REE distribution patterns of the A layer of their host soils. The REEs were fractionated in their transportation in D. linearis. The abundances of heavy rare earth elements (HREEs, Gd to Lu and Y) in the stem, petiole, lamina are lower than those in the root.
Environmental Monitoring↗
Phosphatidylcholine-specific phospholipase C and D in stimulation of RAW264.7 mouse macrophage-like cells by lipopolysaccharide.
The purpose of these studies was to identify the role of phospholipases in the activation of macrophages by lipopolysaccharide (LPS). Tricyclodecan-9-yl-xanthogenate (D609), an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC); butanol, an inhibitor of phosphatidylcholine phospholipase D (PC-PLD); and propranolol, an inhibitor of phosphatidate phosphohydrolase, were used in the study. Treatment of RAW264.7 murine macrophage-like cells with LPS resulted in expression of inducible nitric oxide synthase and tumor necrosis factor-alpha. The expression was partially inhibited by D609, butanol, or propranolol and was completely blocked by the combination of D609 and butanol. RAW264.7 cells constitutively produced low basal levels of diacylglycerol and phosphatidic acid; production of both was significantly increased after stimulation with LPS, reaching a peak in 2-3 min and remaining elevated after 30 min. In LPS-induced RAW264.7 cells, diacylglycerol was suppressed by each of the three inhibitors alone and almost abolished by D609 plus butanol or D609 plus propranolol. Phosphatidic acid was reduced to basal level by butanol after LPS stimulation for 2.5 min and by butanol plus D609 after LPS stimulation for 2.5 or 10 min. Taken together, these data indicate that activation of RAW264.7 cells by LPS can be mediated by the activities of both PC-PLC and PC-PLD.
Adrenergic beta-Antagonists↗
Dentinogenesis imperfecta 1 with or without progressive hearing loss is associated with distinct mutations in DSPP.
Dentinogenesis imperfecta 1 (DGI1, MIM 125490) is an autosomal dominant dental disease characterized by abnormal dentin production and mineralization. The DGI1 locus was recently refined to a 2-Mb interval on 4q21 (ref. 1). Here we study three Chinese families carrying DGI1. We find that the affected individuals of two families also presented with progressive sensorineural high-frequency hearing loss (gene DFNA39). We identified three disease-specific mutations within the dentin sialophosphoprotein gene (DSPP) in these three families. We detected a G-->A transition at the donor-splicing site of intron 3 in one family without DFNA39, a mutation predicted to result in the skipping of exon 3. In two other families affected with both DGI1 and DFNA39, however, we identified two independent nucleotide transversions in exons 2 and 3 of DSPP, respectively, that cause missense mutations of two adjacent amino-acid residues in the predicted transmembrane region of the protein. Moreover, transcripts of DSPP previously reported to be expressed specifically in teeth are also detected in the inner ear of mice. We have thus demonstrated for the first time that distinct mutations in DSPP are responsible for the clinical manifestations of DGI1 with or without DFNA39.
Asian People↗
Adenovirus-mediated interferon-beta gene therapy suppresses growth and metastasis of human prostate cancer in nude mice.
The purpose of this study was to determine the effects of interferon-beta (IFN-beta) gene transfer on the growth of PC3MM2 human prostate cancer cells in nude mice. Intralesional delivery of an adenoviral vector encoding murine IFN-beta (AdIFN-beta), but not a vector encoding bacterial beta-galactosidase (AdLacZ), suppressed PC3MM2 tumors in a dose-dependent manner. At the highest dose (2x10(9) plaque-forming units, PFU), a single injection of AdIFN-beta (but not AdLacZ) suppressed orthotopic PC3MM2 tumors and development of metastasis by 80%, and eradicated the tumors in 20% of mice. Immunohistochemical staining showed that AdIFN-beta-treated tumors contained fewer microvessels, fewer proliferating cells, and more apoptotic cells than did the control tumors. Compared with controls, tumors injected with AdIFN-beta expressed higher levels of IFN-beta and inducible nitric oxide synthase (iNOS) and lower levels of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1). In vitro analysis indicated that expression of bFGF and TGF-beta1 in PC3MM2 cells could be suppressed by the nitric oxide donor sodium nitroprusside. These data suggest that intratumoral delivery of the IFN-beta gene with adenoviral vectors could be an effective therapy for prostate cancer and that tumor suppression by AdIFN-beta correlated with up-regulation of iNOS and down-regulation of angiogenesis.
Adenoviridae↗
Analysis of the interaction of 16S rRNA and cytoplasmic membrane with the C-terminal part of the Streptococcus pneumoniae Era GTPase.
Era, an essential GTPase, plays a regulatory role in several cellular processes. The Era protein of Streptococcus pneumoniae has recently been shown to bind to 16S rRNA and the cytoplasmic membrane. However, exact locations of Era responsible for RNA- and membrane-binding were unknown. To identify the regions in Era that interact with the RNA and membrane, the C-terminal part of S. pneumoniae Era was systematically deleted while the N-terminal part, responsible for the GTPase activity of the protein, was kept intact. The resulting truncated Era proteins were purified and characterized. The C-terminal deletion of 9 or 19 amino-acid residues did not affect 16S rRNA-binding activity while further deletions of the C-terminus (29-114 amino-acid residues) abolished the activity. These results indicate that the integrity of the putative KH domain of Era, spanning the amino-acid residues between approximately 22-83 from the C-terminus, is required for 16S rRNA-binding. Furthermore, the Era proteins with a deletion up to 45 residues from the C-terminus retained membrane-binding activity, but longer deletions significantly reduced the activity. These results indicate that part of the putative KH domain is also required for membrane-binding. Thus, these results indicate for the first time that the regions critical for the membrane- and 16S rRNA-binding activities of Era overlap. The era gene with a deletion of 9 or 19 codons from its 3' terminus complemented an Escherichia coli mutant strain deficient in Era production whereas the genes with longer deletions failed to do so, thereby indicating that the KH domain is essential for Era function. Taken together, the results of this study indicate that the putative KH domain is required for 16S rRNA-binding activity and that part of the KH domain is also required for membrane-binding activity. The results also suggest that the interaction between Era and 16S rRNA is essential for bacterial growth.
Amino Acid Sequence↗