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Q X Li

Publications and source records attributed to Q X Li.

At least 37 records · Page 2Linked to original sources
PubMed2000

Synthesis, characterization, and antibacterial activity of novel Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes with vitamin K3-thiosemicarbazone.

Vitamin K3-thiosemicarbazone (C12H11N3NaO4S2 x 5H2O, abbreviated as VT), a new Schiff base derivative, has been synthesized. Its crystal structure, determined by X-ray diffraction, is triclinic, space group P1. We have also prepared five novel complexes of VT with transition metals: [M(VT)(2)2H2O] x nH2O, (n = 1 and 2 for M = Cu(II) and Zn(II), respectively) and [M'(HVT)2Cl2] x mH2O, (m = 4, 5, and 7 for M' = Co(II), Mn(II), and Ni(II), respectively). These compounds were characterized by IR and UV-Vis spectroscopy, molar conductivity, thermal analyses, complexometric titration, and elemental analysis. In all the complexes, the VT ligand coordinates through sulfur and oxygen atoms, and the geometry around metal atom is best described as octahedral. In vitro tests of antibacterial activity showed that VT and its complexes with Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) all had strong inhibitory actions against G(+) Staphylococcus aureus, G(+) Hay bacillus, and G(-) Escherichia coli.

Anti-Bacterial Agents↗
PubMed2000

Novel Leu723Pro amyloid precursor protein mutation increases amyloid beta42(43) peptide levels and induces apoptosis.

A novel missense mutation, Leu723Pro, in the amyloid precursor protein (APP) gene was discovered in an early-onset Alzheimer's disease family. Expression of L723P mutant APP complementary DNA in CHO cells resulted in a 1.4- to 1.9-fold increased production of the 42(43)-amino acid length amyloid beta peptide compared with the wild-type sequence and was capable of causing apoptosis. The mutation is predicted to alter the luminal transmembrane length and helical arrangement of the APP molecule and thus affect the gamma-secretase cleavage site.

Amino Acid Sequence↗
PubMed2000

Chelation and intercalation: complementary properties in a compound for the treatment of Alzheimer's disease.

Selective application of metal chelators to homogenates of human Alzheimer's disease (AD) brain has led us to propose that the architecture of aggregated beta-amyloid peptide, whether in the form of plaques or soluble oligomers, is determined at least in part by high-affinity binding of transition metals, especially copper and zinc. Of the two metals, copper is implicated in reactive oxygen species generating reactions, while zinc appears to be associated with conformational and antioxidant activity. We tested the copper chelators trientine, penicillamine, and bathophenanthroline for their ability to mobilize brain Abeta as measured against our benchmark compound bathocuproine (BC). All of these agents were effective in solubilizing brain Abeta, although BC was the most consistent across the range of AD brain tissue samples tested. Similarly, all of the copper chelators depleted copper in the high-speed supernatants. BC alone had no significant effect upon zinc levels in the soluble fraction. BC extraction of brain tissue from C100 transgenic mice (which express human Abeta but do not develop amyloid) revealed SDS-resistant dimers as Abeta was mobilized from the sedimentable to the soluble fraction. NMR analysis showed that, in addition to its copper chelating properties, BC interacts with Abeta to form a complex independent of the presence of copper. Such hybrid copper chelating and "chain breaking" properties may form the basis of a rational design for a therapy for Alzheimer's disease.

Alzheimer Disease↗
PubMed2000

Accumulation of insoluble alpha-synuclein in dementia with Lewy bodies.

The alpha-synuclein (alpha SN) protein is thought to play a central role in the pathogenesis of neurodegenerative diseases where it aggregates to form intracellular inclusions. We have used Western blotting to examine the expression levels and solubility of alpha SN in brain homogenates from dementia with Lewy bodies (DLB), Parkinson's disease (PD), Alzheimer's disease (AD), and normal controls using samples from the parahippocampus/transentorhinal cortex. Compared to controls, DLB brains accumulate significantly greater amounts of sodium dodecyl sulfate (SDS)-soluble and SDS-insoluble alpha SN but levels of TBS-soluble alpha SN did not change. Levels of synaptophysin, a marker of synaptic integrity, were significantly lower in DLB cases than in normal aged controls regardless of whether concurrent changes of AD were present. This limbic synaptic dysfunction may contribute to cognitive impairment in DLB. Whether aggregated alpha SN is a cause or effect of the disease process in DLB and PD remains to be determined, but the presence of aggregated alpha SN is consistent with a pathogenesis similar to that associated with aggregates of Abeta amyloid in AD.

Aged↗
PubMed2000

Polychlorinated biphenyls and metals in marine species from French Frigate Shoals, North Pacific Ocean.

Polychlorinated biphenyls (PCBs) and metals were analyzed in coral (Porites lobata), fish (Stegastes fasciolatus), crab (Grapsus tenuicrustatus), and sediment samples collected from Tern Island, and the reference samples from Trig and La Perouse Islands. All three islands are part of French Frigate Shoals, a national wildlife refuge in the North Pacific Ocean. Average concentrations of total PCBs ranged from 154 to 274 ng/g in the sediments, from 120 to 267 ng/g in the corals, from 387 to 4,500 ng/g in the crabs, and 1,340 to 46,000 ng/g, dry weight, in the fishes. High concentrations in marine species indicate there is PCB source(s) in French Frigate Shoals, especially Tern Island. Tetra- and pentachlorobiphenyls were 64-66% of the total PCB levels in the sediments, and they accounted for 57-65% of total PCBs in the corals. Penta- and hexachlorobiphenyls were 76-84% of total PCBs in the fishes, and they accounted for 79-85% in the crab samples. The sediment and coral were predominated by lower chlorinated PCB congeners, whereas the fish and crab bioaccumulated mainly higher chlorinated congeners. Selenium concentrations (16-23 microg/g) in sediments were much higher than some reported baseline values (0.4-2.5 microg/g). The average concentrations of arsenic, cadmium, lead, and selenium in the coral and fish were about equal to or less than those in the sediments. Concentrations of arsenic and cadmium in the crabs (49-51 and 3-4 microg/g, respectively) were approximately twofold of those in the sediments.

Animals↗
PubMed2000

Pressurized fluid extraction for quantitative recovery of chloroacetanilide and nitrogen heterocyclic herbicides in soil.

Pressurized fluid extraction (PFE) is a new sample extraction method operated at elevated temperatures and pressures with liquid solvents. The use of PFE was investigated for the extraction of four Hawaiian clayey soils fortified with the selected chloroacetanilide and nitrogen heterocyclic herbicides Alachlor, Bromacil, Hexazinone, Metribuzin, and Tebuthiuron. The effects of operation temperature, pressure, flush volume, and static cycles on PFE performance were studied. Water was the most effective modifier of PFE for quantitative recoveries of the five herbicides in soils. The simple extraction method required pretreatment of the soil with 37.6% water and subsequent two-static-cycle extraction with a total of 32 mL of acetone at 1500 psi and 100 degrees C. Average recoveries of Alachlor, Bromacil, Hexazinone, Metribuzin, and Tebuthiuron ranged from 93 to 103% by the water-assisted PFE, compared with only 68-83% recoveries of the corresponding chemicals when no water was used. The extraction time and total organic solvent consumption were reduced from 18 h and 300 mL by Soxhlet to 22 min or less and 80 mL or less of organic solvent by PFE.

Acetamides↗
PubMed2000

Derivation and properties of recombinant Fab antibodies to coplanar polychlorinated biphenyls.

Recombinant Fab antibodies (rFabs) specific for coplanar polychlorinated biphenyls (PCBs) were derived from a hybridoma cell line (Chiu et al. Anal. Chem. 1995, 67, 3829-3839). Immunoglobulin V(H)-C(H1) and V(L)-C(L) sequences from S2B1 messenger RNA were amplified by PCR and cloned into the M13 phagemid vector pComb3H. Phage displaying rFab were enriched by panning on a PCB hapten conjugate and expressed as soluble rFabs in Escherichia coli XL-1 Blue. Two rFab clones competitively bound PCBs 77 and 126 with half-maximal inhibition (I(50)) of 10-13 ppb in indirect and direct enzyme immunoassays (EIAs), with selectivity nearly identical to that of whole S2B1 IgG and its Fab fragments prepared by papain digestion. These results, and comparison of N-terminal amino acid sequences of MAb S2B1 and the rFab, indicated that rFab S2B1 is a functional copy of the MAb. The rFab S2B1 sequences have 75-89% sequence identity with antibodies that bind nitrophenyl haptens and are being used to construct a three-dimensional computational model of the PCB binding site.

Amino Acid Sequence↗
PubMed2000

Development of an enzyme-linked immunosorbent assay for the insecticide imidacloprid.

Enzyme-linked immunosorbent assays (ELISAs) were developed for imidacloprid, a neonicotinoid insecticide. Haptens were designed in such ways that spacer arms were introduced on either the pyridinyl or the imidazolidinyl ring of imidacloprid. Two sets of polyclonal antibodies were raised from rabbits immunized with two different immunogens and were characterized with an indirect ELISA format. Cross-reactivities and effects of organic solvents on the assays were evaluated. One set of antibodies shows approximately equal cross-reactivities to imidacloprid and its major metabolites with half-maximum inhibition concentrations (I(50)) of 73-88 ppb. Another is specific to imidacloprid with an I(50) of 35 ppb. The assay was initially applied to the analysis of imidacloprid in fortified water, coffee cherry, and bean extracts.

Enzyme-Linked Immunosorbent Assay↗
PubMed1999

Alpha-synuclein accumulates in Lewy bodies in Parkinson's disease and dementia with Lewy bodies but not in Alzheimer's disease beta-amyloid plaque cores.

A growing body of evidence suggests that the non-Abeta component of Alzheimer's disease amyloid precursor protein (NACP) or alpha-synuclein contributes to the neurodegenerative processes in Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In the present study antisera to the N terminus and the NAC domain of the alpha-synuclein protein were employed to elucidate the expression pattern in brains of patients with AD, PD, DLB and control specimen. Alpha-synuclein exhibited an overall punctuate expression profile compatible with a synaptic function. Interestingly, while Lewy bodies were strongly immunoreactive, none of the alpha-synuclein antisera revealed staining in mature beta-amyloid plaques in AD. These observations suggest that alpha-synuclein does not contribute to late neurodegenerative processes in AD brains.

Alzheimer Disease↗
PubMed1999

Monoclonal antibody-based ELISAs for part-per-billion determination of polycyclic aromatic hydrocarbons: effects of haptens and formats on sensitivity and specificity.

As a first step toward developing sensitive enzyme-linked immunosorbent assays (ELISAs) for multianalyte detection of polycyclic aromatic hydrocarbons (PAHs), haptens with different lengths of carboxylic acid spacers at various positions were derived from naphthalene, fluorene, anthracene, phenanthrene, pyrene, fluoranthene, chrysene, and benzo[a]pyrene (BaP). These haptens were coupled with bovine serum albumin (BSA) to form competitor conjugates. All of these haptens were recognized to different extents by monoclonal antibodies (MAbs) 4D5 and 10C10 originally derived by Gomes and Santella (Chem. Res. Toxicol. 1990, 3, 307-310). The most sensitive indirect ELISAs were obtained by coating wells with the least competitive conjugates. Direct ELISAs using horseradish peroxidase conjugates of pyrene and BaP were less sensitive. The MAbs bound BaP with spacers at either C1 or C6. The cross-reactivity profiles of the eight PAHs were different with each PAH-BSA conjugate used as coating antigen. The ELISA results for BaP closely correlated with those by gas chromatography (GC), but the detection limit of the ELISA was approximately 150-fold more sensitive than that of GC, with 2-600 nM spike recoveries of 80-127% from human urine and canal and tap water.

Antibodies, Monoclonal↗
PubMed1999

The amyloid precursor protein of Alzheimer disease in human brain and blood.

Studies of the metabolism and function of the amyloid precursor protein (APP) and its proteolytic fragment A beta in cultured cells, transgenic mice, and post-mortem brain tissue have advanced our understanding of Alzheimer disease (AD). However, the molecular pathogenesis of the disease is still not clear, and we are a long way from finding a cure for the disease. Studies carried out on human platelets and leukocytes have also helped shed light on APP and A beta metabolism and function. Platelet and leukocyte APP isoforms are processed using mechanisms similar to those in neuronal cells to generate A beta and soluble forms of APP. The activation of platelets and leukocytes leads to the secretion of APP and A beta, resulting in higher levels of these proteins in serum. APP and A beta in the circulation may be involved in the regulation of platelet function and in the modulation of immune responses. Because human platelets and lymphocytes produce all forms of APP and secrete amyloidogenic A beta peptides, these tissues may be useful in monitoring responses to therapeutic interventions directed at APP metabolism. Although not of neuronal origin, further studies on the more accessible ex vivo tissues, including platelets and leukocytes and other blood components, may reveal potential peripheral markers for AD and will further our understanding of the molecular pathogenesis of AD.

Alzheimer Disease↗
PubMed1999

Non-Abeta component of Alzheimer's disease amyloid (NAC) revisited. NAC and alpha-synuclein are not associated with Abeta amyloid.

alpha-Synuclein (alphaSN), also termed the precursor of the non-Abeta component of Alzheimer's disease (AD) amyloid (NACP), is a major component of Lewy bodies and Lewy neurites pathognomonic of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). A fragment of alphaSN termed the non-Abeta component of AD amyloid (NAC) had previously been identified as a constituent of AD amyloid plaques. To clarify the relationship of NAC and alphaSN with Abeta plaques, antibodies were raised to three domains of alphaSN. All antibodies produced punctate labeling of human cortex and strong labeling of Lewy bodies. Using antibodies to alphaSN(75-91) to label cortical and hippocampal sections of pathologically proven AD cases, we found no evidence for NAC in Abeta amyloid plaques. Double labeling of tissue sections in mixed DLB/AD cases revealed alphaSN in dystrophic neuritic processes, some of which were in close association with Abeta plaques restricted to the CA1 hippocampal region. In brain homogenates alphaSN was predominantly recovered in the cytosolic fraction as a 16-kd protein on Western analysis; however, significant amounts of aggregated and alphaSN fragments were also found in urea extracts of SDS-insoluble material from DLB and PD cases. NAC antibodies identified an endogenous fragment of 6 kd in the cytosolic and urea-soluble brain fractions. This fragment may be produced as a consequence of alphaSN aggregation or alternatively may accelerate aggregation of the full-length alphaSN.

Alzheimer Disease↗
PubMed1999

Intracellular accumulation of detergent-soluble amyloidogenic A beta fragment of Alzheimer's disease precursor protein in the hippocampus of aged transgenic mice.

To study amyloid beta-protein (A beta) production and aggregation in vivo, we created two transgenic (Tg) mouse lines expressing the C-terminal 100 amino acids of human amyloid precursor protein (APP): Tg C100.V717F and Tg C100.WT. Western blot analysis showed that human APP-C100 and A beta were produced in brain and some peripheral tissues and A beta was produced in serum. Using antibodies specific for the A beta C terminus we found that Tg C100.V717F produced a 1.6-fold increase in A beta42/A beta40 compared with Tg C100.WT. Approximately 30% of total brain A beta (approximately 122 ng/g of wet tissue) was water-soluble. The remaining 70% of A beta partitioned into the particulate fraction and was completely sodium dodecyl sulfate-soluble. In contrast, human Alzheimer's disease brain has predominantly sodium dodecyl sulfate-insoluble A beta. Immunohistochemistry with an A beta(5-8) antibody showed that A beta or A beta-containing fragments accumulated intracellularly in the hippocampus of aged Tg C100.V717F mice. The soluble A beta levels in Tg brain are similar to those in normal human brain, and this may explain the lack of microscopic amyloid deposits in the Tg mice. However, this mouse model provides a system to study the intracellular processing and accumulation of A beta or A beta-containing fragments and to screen for compounds directed at the gamma-secretase activity.

Aging↗
PubMed1999

An inducible human immunodeficiency virus type 1 (HIV-1) vector which effectively suppresses HIV-1 replication.

Recently, gene therapy vectors based upon the human immunodeficiency virus type 1 (HIV-1) genome have been developed. Here, we create an HIV-1 vector which is defective for all HIV-1 genes, but which maintains cis-acting elements required for efficient packaging, infection, and expression. In T cells transduced by this vector, vector expression is low but efficiently induced following HIV-1 infection. Remarkably, although the HIV-1 vector does not contain specific anti-HIV-1 therapeutic genes, the presence of the vector alone is sufficient to inhibit the spread of HIV-1 infection. The mechanism of inhibition is likely to be at the level of competition for limiting substrates required for either efficient packaging or reverse transcription, thereby selecting against propagation of wild-type HIV-1. These results provide proof of a concept for potential application of a novel HIV-1 vector in HIV-1 disease.

Cell Line, Transformed↗
PubMed1999

Demethylation capacity of human fetal adrenal mitochondrial cytochrome P-450 in vitro.

AIM: To explore the capacity and characteristics of adrenal mitochondria to metabolize xenobiotics in vitro in human fetus. METHODS: Subcellular fractions of fetal adrenal were prepared by differential centrifugation. Mitochondrial P-450 system was proved by spectral analyses and SDS-PAGE. The formaldehyde formation contents were measured with Nash reagent. RESULTS: The erythromycin N-demethylation linearly increased in the protein concentration (1-4 mg)- and incubation time (10-30 min)-dependent manners. A typical concentration-effect relationship appeared with erythromycin 0.067-1 mmol.L-1 and a positive correlation (r = 0.641, P < 0.05) existed between erythromycin N-demethylation and gestation months. The N-demethylation values (nmol.s-1/g protein) of erythromycin (2.7 +/- 0.8), benzfetamine (1.1 +/- 0.5), and aminophenazone (0.9 +/- 0.4) in mitochondria were 89% (P > 0.05), 162% (P < 0.01), and 62% (P < 0.01), respectively, of those in microsomes. There was correlation between mitochondria and microsomes in the N-demethylation of erythromycin (r = 0.708, P < 0.05) and benzfetamine (r = 0.707, P < 0.05). Troleandomycin stimulated erythromycin N-demethylation in adrenal mitochondria as well as in adrenal and liver microsomes in vitro. CONCLUSION: Fetal adrenal mitochondria, with multiple P-450 isoforms and greater capacity of demethylation, play a role in drug-metabolism during fetal development.

Adrenal Glands↗
PubMed1998

Processing of the Alzheimer's disease amyloid precursor protein in Pichia pastoris: immunodetection of alpha-, beta-, and gamma-secretase products.

betaA4 (Abeta) amyloid peptide, a major component of Alzheimer's disease (AD) plaques, is a proteolytic product of the amyloid precursor protein (APP). Endoproteases, termed beta- and gamma-secretase, release respectively the N- and C-termini of the peptide. APP default secretion involves cleavage within the betaA4 domain by alpha-secretase. To study the conservation of APP processing in lower eukaryotes, the yeast Pichia pastoris was transfected with human APP695 cDNA. In addition to the full-length integral transmembrane protein found in the cell lysate, soluble/secreted APP (sAPP) was detected in the culture medium. Most sAPP comprised the N-terminal moiety of betaA4 and corresponds to sAPPalpha, the product of alpha-secretase. The culture medium also contained minor secreted forms detected by a monoclonal antibody specific for sAPPbeta (the ectodomain released by beta-secretase cleavage). Analysis of the cell lysates with specific antibodies also detected membrane-associated C-terminal fragments corresponding to the products of alpha and beta cleavages. Moreover, immunoprecipitation of the culture medium with three antibodies directed at distinct epitopes of the betaA4 domain yielded a 4 kDa product with the same electrophoretic mobility as betaA4 synthetic peptide. These results suggest that the alpha-, beta-, and gamma-secretase cleavages are conserved in yeast and that P. pastoris may offer an alternative to mammalian cells to identify the proteases involved in the generation of AD betaA4 amyloid.

Alzheimer Disease↗