Biomedical subjects

Lei Ma

Publications and source records attributed to Lei Ma.

At least 19 recordsLinked to original sources

PubMed2006

Cloning and characterization of 40S ribosomal protein S4 gene from Culex pipiens pallens.

The 40S ribosomal protein S4 gene (RPS4) has been cloned from Culex pipiens pallens. An open reading frame (ORF) of 789 bp was found to encode a putative 262 amino acid protein. The deduced amino acid sequence shares 96% and 91% identity with RPS4 genes from Aedes and Anopheles respectively. Transcript expression of RPS4 was determined by real-time PCR in all life stages of deltamethrin-susceptible and -resistant strains. The results demonstrated that this gene is expressed at all developmental stages. Meanwhile, in pupae and adults, RPS4 is overexpressed in deltamethrin-resistant strain than in -susceptible strain. Our data for the first time suggests that increased expression of the RPS4 gene may play some role in the development of deltamethrin resistance in C. pipiens pallens.

Amino Acid Sequence↗

PubMed2006

LRRTM3 promotes processing of amyloid-precursor protein by BACE1 and is a positional candidate gene for late-onset Alzheimer's disease.

Rare familial forms of Alzheimer's disease (AD) are thought to be caused by elevated proteolytic production of the Abeta42 peptide from the beta-amyloid-precursor protein (APP). Although the pathogenesis of the more common late-onset AD (LOAD) is not understood, BACE1, the protease that cleaves APP to generate the N terminus of Abeta42, is more active in patients with LOAD, suggesting that increased amyloid production processing might also contribute to the sporadic disease. Using high-throughput siRNA screening technology, we assessed 15,200 genes for their role in Abeta42 secretion and identified leucine-rich repeat transmembrane 3 (LRRTM3) as a neuronal gene that promotes APP processing by BACE1. siRNAs targeting LRRTM3 inhibit the secretion of Abeta40, Abeta42, and sAPPbeta, the N-terminal APP fragment produced by BACE1 cleavage, from cultured cells and primary neurons by up to 60%, whereas overexpression increases Abeta secretion. LRRTM3 is expressed nearly exclusively in the nervous system, including regions affected during AD, such as the dentate gyrus. Furthermore, LRRTM3 maps to a region of chromosome 10 linked to both LOAD and elevated plasma Abeta42, and is structurally similar to a family of neuronal receptors that includes the NOGO receptor, an inhibitor of neuronal regeneration and APP processing. Thus, LRRTM3 is a functional and positional candidate gene for AD, and, given its receptor-like structure and restricted expression, a potential therapeutic target.

Alzheimer Disease↗

PubMed2006

Cloning and overexpression of ribosomal protein L39 gene from deltamethrin-resistant Culex pipiens pallens.

The complete sequence of ribosomal protein L39 has been cloned from deltamethrin-resistant strain of Culex pipiens pallens (DR1 strain). Quantitative RT-PCR analysis indicated that the RPL39 transcription level was 23.4 times higher in DR1 strain than in susceptible strain at 4th instar larvae. The RPL39 expression was also found to be consistently higher throughout the life cycle of DR1 strain. A protein of predicted size 17 kDa has been detected by Western blotting in RPL39-transfected mosquito C6/36 cells. These RPL39-transfected cells also showed enhanced deltamethrin resistance compared to plasmid vector-transfected cells as determined by methyl tritiated thymidine ((3)H-TdR) incorporation. These results indicate that RPL39 is expressed at higher levels in DR1 strain, and may confer some insecticide resistance in Cx. pipiens pallens.

Actins↗

PubMed2006

Anidulafungin pharmacokinetics and microbial response in neutropenic mice with disseminated candidiasis.

Candidemia is often fatal, especially in patients with persistent neutropenia. New therapies are needed. We performed 24-h pharmacodynamic studies to compare the efficacies of anidulafungin, fluconazole, and amphotericin B in neutropenic mice with disseminated candidiasis caused by one of three strains of Candida glabrata. Anidulafungin produced a maximal fungal kill (E(max)) of 1.4 to 1.9 log(10) CFU/g in kidneys and was not influenced by resistance to either fluconazole or amphotericin B. Fluconazole produced an E(max) of 1.3 log(10) CFU/g in mice infected with fluconazole-susceptible C. glabrata, but the E(max) was 0 for mice infected with a C. glabrata strain that had a fluconazole MIC of >/=32 mg/liter. Amphotericin B achieved an E(max) of 4.2 log(10) CFU/g in mice infected with amphotericin B-susceptible C. glabrata, but the E(max) was 0 for mice infected with a C. glabrata strain with an amphotericin B MIC of 2 mg/liter. In all instances, anidulafungin's maximal microbial kill was superior to that of fluconazole. Next, we performed a 96-h anidulafungin pharmacokinetic-pharmacodynamic study. Anidulafungin exhibited delayed peak concentrations in kidneys compared to those in serum, after which the concentrations declined, with a serum terminal half-life of 21.6 (+/-4.6) h. This was accompanied by a persistent 96-h decrease in the kidney fungal burden after treatment with a single anidulafungin dose of >/=8 mg/kg of body weight. This pharmacokinetic-pharmacodynamic picture of anidulafungin persistence in tissues and the resultant persistent fungal decline should be exploited to improve the efficacy of anidulafungin therapy for candidemia.

Algorithms↗

PubMed2006

Daturametelins H, I, and J: three new withanolide glycosides from Datura metel L.

Three new withanolide glycosides named daturametelins H-J (1-3), together with two known ones, daturataturin A (4) and 7,27-dihydroxy-1-oxowitha-2,5,24-trienolide (5), were isolated from the MeOH extract of the aerial parts of Datura metel L. (Solanaceae). Their structures were determined mainly by spectroscopic techniques including 2D-NMR (HMBC, HMQC, (1)H,(1)H-COSY, NOESY) and MS experiments. Compounds 1-5 were tested for their antiproliferative activity towards the human colorectal carcinoma (HCT-116) cell line. The nonglycosidic compound 5 exhibited the highest activity of the tested withanolides, with an IC(50) value of 3.2+/-0.2 microM (Table 3).

Antineoplastic Agents, Phytogenic↗

PubMed2006

A zwitterionic alkaloid, containing a rare cyclopentadienyl anion unit, from the stem barks of Daphniphyllum macropodum Miq.

A new Daphniphyllum alkaloid daphnicyclidin L (1), containing a rare cyclopentadienyl anion, which is stabilized as a zwitterion by an internal iminium counterion, was isolated from the stem barks of Daphniphyllum macropodum Miq., together with four known alkaloids: daphnicyclidin D (2), daphnicyclidin H (3), deoxyyuzurimine (4), and yuzurimine (5). The structures were elucidated on the basis of spectroscopic data. The configuration of 1 was elucidated by single-crystal X-ray diffraction crystallography.

Alkaloids↗

PubMed2006

Cassane diterpene-lactones from the seed of Caesalpinia minax HANCE.

Five new neocaesalpins, named neocaesalpin J-N (1-5, resp.), along with the known neocaesalpin A and eight known furanditerpenoids, namely epsilon-caesalpin, 7-acetoxy-epsilon-caesalpin, 14-deoxy-epsilon-caesalpin, caesalmins D-F, and bonducellins C and D, were isolated from the seeds of Caesalpinia minax HANCE. Their structures were determined on the basis of spectroscopic analyses.

Caesalpinia↗

PubMed2006

Sex differences in CYP3A activity using intravenous and oral midazolam.

BACKGROUND: Studies examining sex differences in CYP3A activity have produced conflicting results. Our objective is to investigate whether sex differences exist in CYP3A activity as assessed by intravenous (IV) or oral midazolam pharmacokinetic analysis in healthy volunteers. METHODS: Data from 13 previous studies were used. A single dose of IV midazolam (0.025 mg/kg) was administered to 66 white adults (37 women and 29 men; mean age, 36.3+/-7.7 years). A single dose of oral midazolam, 0.075 mg/kg (5 studies), 0.15 mg/kg (1 study), or 5 mg (1 study), was administered to 72 adults (71 white and 1 Asian; 37 women and 35 men; mean age, 38.3+/-8.9 years). Pharmacokinetic parameters were determined via population methods by use of a nonparametric adaptive grid program and a 2-compartment IV and 1-compartment oral absorption model. The maximum a posteriori probability Bayesian method was used to estimate each subject's pharmacokinetic parameters. Monte Carlo simulation was performed to determine the probability distribution of the area under the concentration-time curves (AUCs). RESULTS: Women exhibited 11% higher mean weight-corrected total body midazolam clearance and 28% higher oral clearance compared with men (P<or=.01). The median AUC of IV midazolam was 0.05 mg.h/L (range, 0.02-0.14 mg.h/L) in women and 0.06 mg.h/L (range, 0.02-0.14 mg.h/L) in men. The median AUC of oral midazolam was 0.11 mg.h/L (range, 0.02-0.60 mg.h/L) in women and 0.12 mg.h/L (range, 0.04-0.45 mg.h/L) in men. CONCLUSIONS: Although women showed significantly greater hepatic and intestinal CYP3A activity, only a minor sex difference in AUC was noted. Therefore the observed disparity may be of negligible clinical importance.

Administration, Oral↗

PubMed2006

Larvicidal activity of extracts of Ginkgo biloba exocarp for three different strains of Culex pipiens pallens.

Ethanolic extracts from the Ginkgo biloba L. exocarp from the Chinese ginkgo were assayed against larvae of three strains of Culex pipiens pallens Coquillett. The chemical compositions were detected using a Hewlett-Packard 6890/5973 mass spectrometric detector. The larvicidal bioassay was carried out according to the recommendations of the World Health Organization. The analysis of the essential oil of ginkgo exocarp showed that its major components are ginkgo acid (85.3%) and ginkgo phenolic (5.69%). The larvicidal bioassay showed that extracts of ginkgo exocarp have LC50 of 18.6, 12.7, and 25.0 mg/liter for deltamethrin-susceptible, deltamethrin-resistant, and field strains, respectively. The acute toxicity concentrations of the ginkgo extracts that killed 50% (LD50) of Wistar rats within 2 wk and young carp within 96 h were 4947.2 mg/kg and 557.9 mg/liter, respectively. These results are promising in creating new, effective, and affordable approaches to mosquito control.

Animals↗

PubMed2006

[Effects of acupuncture at Weizhong (BL40) on brain function with PET/CT].

OBJECTIVE: To observe the effect of needling at Weizhong (BL 40) acupoint in inducing metabolic changes in brain with positron emission tomography and dynamic contrast (PET/CT) imaging for exploring the mechanism of central regulation of acupuncture. METHODS: PET/CT was performed before and during needling Weizhong acupoint of right leg by electro-acupuncture in 8 healthy volunteers, and also in other 8 subjects without any acupoint stimulation for control. Difference of brain functional images between the two groups before and during needling was analyzed by pairing t-test with statistical parametric mapping. RESULTS: The needling evoked mean activated cerebral functional regions were: left Broadmann area (BA) 10, 11, 22, 38, 39, 40, 44-46, right BA10, bilateral BA18, 19, and left cerebellar cortex, claustrum and insula (t > 3.36, P < 0.01, k >30 voxels); its mean inhibited brain functional regions were: bilateral BA24, left BA7, 8, 19, 40, right BA 1, 3, 6, 20, 44, and left substantia nigra. CONCLUSION: There is a certain connection between Weizhong acupoint and the brain. Needling this acupoint could exert effects through activating or inhibiting brain function in specific regions and neurohumoral regulation. One of the central regulation mechanisms of acupuncture was functional activation in superior, middle, and inferior frontal gyrus, insula and cerebellum and functional inhibition in callosal gyrus, lobi parietalis and substantia nigra. This study further demonstrated PET/CT is useful in revealing TCM meridian theory and could provide objective proof of central regulation for acupuncture treatment.

Acupuncture↗

PubMed2005

Increased nuclear factor-erythroid 2 p45-related factor 2 activity protects SH-SY5Y cells against oxidative damage.

The ability of cells to control the balance between the generation and quenching of reactive oxygen species is important in combating potentially damaging effects of oxidative stress. One mechanism that cells use to maintain redox homeostasis is the antioxidant response pathway. Antioxidant response elements (AREs) are cis-acting elements located in regulatory regions of antioxidant and phase II detoxification genes. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is a member of the Cap 'n' Collar family of transcription factors that binds to the ARE and regulates the transcription of specific ARE-containing genes such as NAD(P)H:quinone oxidoreductase 1, glutamylcysteine synthetase and heme oxygenase. Activation of Nrf2 results in release from its negative repressor, Kelch-like ECH-associated protein 1 (Keap1), and allows Nrf2 to translocate into the nucleus to induce gene expression. In this study, we demonstrate that increasing Nrf2 activity by various methods, including chemical induction, Nrf2 overexpression or Keap1 siRNA knockdown, protects cells against specific types of oxidative damage. Cells were protected against 6-hydroxydopamine- and 3-morpholinosydnonimine-mediated toxicity but not against 1-methyl-1-4-phenylpyridinium toxicity. As oxidative stress is a hallmark of several neurodegenerative disorders, including Parkinson's disease, pharmacological agents that selectively target the Keap1-Nrf2 pathway may provide a novel neuroprotective strategy for the treatment of these diseases.

1-Methyl-4-phenylpyridinium↗

PubMed2005

Serine proteinase over-expression in relation to deltamethrin resistance in Culex pipiens pallens.

Two serine proteinase genes were isolated from Culex pipiens pallens as significantly up-regulated genes in a deltamethrin-resistant strain through a combination of suppression substractive hybridization and gene expression profiling by macroarrays. These two genes were found to be expressed at least threefold higher in the resistant strain than in the susceptible one. By using rapid amplification of cDNA ends to screen the constructed cDNA library, we cloned these two sequences. There were 909 bp with an open reading frame of 786 bp in the sequence of trypsin cDNA (GenBank/NCBI AF468495), the deduced protein had 261 amino acids, which was most similar to the trypsin gene of Anopheles gambiae. There were 992 bp with an open reading frame of 816 bp in the chymotrypsin cDNA (GenBank/NCBI AY034060), and its deduced amino acid sequence had 271 amino acids, which was most similar to the chymotrypsin-like protein from Aedes aegypti. The two genes were stably expressed in mosquito C6/36 cells, and the expected 29 and 30 kDa bands were shown with Western blot, respectively. In these cells, after deltamethrin treatment, they had protective effects on the viability. The results indicate that trypsin and chymotrypsin were more highly expressed in the deltamethrin-resistant strain, and was related to insecticide resistance in mosquitoes, Cx. pipiens pallens.

Amino Acid Sequence↗

PubMed2005

Bidirectional labeling and registration scheme for grayscale image segmentation.

In this paper, we introduce a new image segmentation scheme that is based on bidirectional labeling and registration and prove that its segmentation performance is equivalent to that of the conventional watershed segmentation algorithm. The proposed bidirectional labeling and registration scheme, which we refer to as bidirectional labeling and registration scheme (BIDS), involves only linear scans of image pixels. It uses one-dimensional operations rather than the queues that are used in traditional segmentation algorithms, which are two-dimensional problems. BIDS also provides unique labels for individual homogeneous regions. In addition to achieving the same segmentation results, BIDS is four times less computationally complex than the conventional watershed by immersion technique.

Algorithms↗

PubMed2005

Cloning and overexpression of CYP6F1, a cytochrome P450 gene, from deltamethrin-resistant Culex pipiens pallens.

CYP6F1 (GenBank/EMBL accession No. AY662654), a novel gene with a complete encoding sequence in the cytochrome P450 family 6, was cloned and sequenced from deltamethrin-resistant 4th instar larvae of Culex pipiens pallens. The cDNA sequence of CYP6F1 has an open reading frame of 1527 bp, which encodes a putative protein of 508 amino acid residues. The deduced amino acid sequence of CYP6F1 indicated that the encoded P450 has conserved domains of a putative membrane-anchoring signal, putative reductase-binding sites, a typical heme-binding site, an ETLR motif and substrate recognition sites. Semi-quantitative RT-PCR analysis indicated that the CYP6F1 gene was expressed to a greater extent in the deltamethrin-resistant strain than in the susceptible strain of Cx. pipiens pallens. The expression levels of the CYP6F1 gene in the deltamethrin-resistant 1st, 2nd, 3rd, 4th instar larvae and adult female mosquitoes differed, with highest expression levels in the 4th instar larvae. In addition, the CYP6F1 gene was stably expressed in mosquito C6/36 cells, and the expected 61.2 kDa band was identified by Western blotting. The cells transfected with CYP6F1 had an increased resistance to deltamethrin as compared with control cells. These results indicate that CYP6F1 is expressed at higher levels in the deltamethrin-resistant strain, and may confer some insecticide resistance in Cx. pipiens pallens.

Amino Acid Sequence↗

PubMed2004

Solution-phase synthesis of single-crystalline iron phosphide nanorods/nanowires.

A solution-phase route for the preparation of single-crystalline iron phosphide nanorods and nanowires is reported. We have shown that the mixture of trioctylphosphine oxide (TOPO) and trioctylphosphine (TOP), which are commonly used as the solvents for semiconductor nanocrystal synthesis, is not entirely inert. In the current process, TOP, serving as phosphor source, reacts with Fe precursors to form FeP nanostructures with large aspect ratios. In addition, the experimental results show that both TOP and TOPO are necessary for the formation of FeP nanowires and their ratio appears to control the morphology of the produced FeP structures. A possible growth mechanism is discussed.

Journal Article↗

PubMed2003

DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation.

Disrupted-In-Schizophrenia 1 (DISC1) is a novel gene associated with schizophrenia by multiple genetic studies. In order to determine how mutations in DISC1 might cause susceptibility to schizophrenia, we undertook a comprehensive study of the cellular biology of DISC1 in its full-length and disease-associated mutant forms. DISC1 interacts by yeast two-hybrid, mammalian two-hybrid, and co-immunoprecipitation assays with multiple proteins of the centrosome and cytoskeletal system, including MIPT3, MAP1A and NUDEL; proteins which localize receptors to membranes, including alpha-actinin2 and beta4-spectrin; and proteins which transduce signals from membrane receptors, including ATF4 and ATF5. Truncated mutant DISC1 fails to interact with ATF4, ATF5 or NUDEL. Deletion mapping demonstrated that DISC1 has distinct interaction domains: MAP1A interacts via its LC2 domain with the N-terminus of DISC1, whereas MIPT3 and NUDEL bind via their C-terminal domains to the central coiled-coil domain of DISC1, and ATF4/5 bind via their C-terminal domains to the C-terminus of DISC1. In its full-length form, DISC1 protein localizes to predominantly perinuclear punctate structures which extend into neurites in some cells; mutant truncated DISC1, by contrast, is seen in a diffuse pattern throughout the cytoplasm and abundantly in neurites. Both forms co-localize with the centrosomal complex, although truncated less abundantly than full-length DISC1. Although both full-length and mutant DISC1 are found in microtubule fractions, neither form of DISC1 appears to bind directly to microtubules, but rather do so in a MIPT3-dependent fashion that is stabilized by taxol. Based on these data, we propose that DISC1 is a multifunctional protein whose truncation contributes to schizophrenia susceptibility by disrupting intracellular transport, neurite architecture and/or neuronal migration, all of which have been hypothesized to be pathogenic in the schizophrenic brain.

Activating Transcription Factors↗

PubMed2003

DISC1 (Disrupted in Schizophrenia-1) is expressed in limbic regions of the primate brain.

Disrupted in Schizophrenia-1 (DISC1) was identified as truncated by a balanced translocation segregating with schizophrenia and other major mental illness in a large Scottish family. As a step in evaluating the function of DISC1 and its potential role in human schizophrenia, we have determined its regional expression in the primate brain by in situ hybridization. DISC1 expression is highly localized, with most prominent expression in the dentate gyrus of the hippocampus and lateral septum, and lower levels of expression in the cerebral cortex, amygdala, paraventricular hypothalamus, cerebellum, interpeduncular nucleus, and subthalamic nucleus. Given that many of these regions have been implicated in schizophrenia pathogenesis, these results suggest brain circuits through which DISC1 truncation may predispose to schizophrenia.

Animals↗

PubMed2002

Multifocal electroretinogram: age-related changes for different luminance levels.

BACKGROUND: Age-related changes in the first-order multifocal electroretinogram (mfERG) responses were measured for two different luminance levels (200 and 700 cd.m(-2)). The relative contribution of optical and neural factors to senescent change in response was evaluated. METHODS: Data were obtained from one eye of each of 71 normal phakic subjects, age 9-80 years. The mfERG responses were recorded with the 7" stimulus-refractor unit (EDI) and VERIS 4.3 using the following protocol: bipolar contact lens, 103 hexagons, consecutive stimulation with 200 and 700 cd.m(-2), pupils > or =6 mm, amplification of 10(5), filter cut-offs at 10 and 300 Hz. RESULTS: Age-correlated decreases in amplitude and response density and increases in P1 implicit time were found for both luminance levels. The mean response density (nV.deg(-2)) was higher for the 700 cd.m(-2) stimulus, but the rate of change with age was not significantly different from that obtained with the 200 cd.m(-2) stimulus. Implicit time was not significantly different for the two light levels, nor was the rate of change with age. The decrease in response density and the increase in implicit time with age were significant across all retinal regions, dividing the 50 deg stimulus into six concentric rings. Age-related change in response density was greatest for the central retina and decreased with increasing retinal eccentricity. CONCLUSION: Log mfERG response changes linearly as a function of age. Analyses of the effects of reduced ocular media transmission and increased stray light, along with ancillary data obtained from pseudophakes, imply that age-related changes in the mfERG are due to both optical and neural factors.

Adolescent↗