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Biomedical subjects

C Lu

Publications and source records attributed to C Lu.

At least 37 records · Page 2Linked to original sources
PubMed2001

An amplified fragment length polymorphism map of the silkworm.

The silkworm (Bombyx mori L.) is a lepidopteran insect with a long history of significant agricultural value. We have constructed the first amplified fragment length polymorphism (AFLP) genetic linkage map of the silkworm B. mori at a LOD score of 2.5. The mapping AFLP markers were genotyped in 47 progeny from a backcross population of the cross no. 782 x od100. A total of 1248 (60.7%) polymorphic AFLP markers were detected with 35 PstI/TaqI primer combinations. Each of the primer combinations generated an average of 35.7 polymorphic AFLP markers. A total of 545 (44%) polymorphic markers are consistent with the expected segregation ratio of 1:1 at the significance level of P = 0.05. Of the 545 polymorphic markers, 356 were assigned to 30 linkage groups. The number of markers on linkage groups ranged from 4 to 36. There were 21 major linkage groups with 7-36 markers and 9 relatively small linkage groups with 4-6 markers. The 30 linkage groups varied in length from 37.4 to 691.0 cM. The total length of this AFLP linkage map was 6512 cM. Genetic distances between two neighboring markers on the same linkage group ranged from 0.2 to 47 cM with an average of 18.2 cM. The sex-linked gene od was located between the markers P1T3B40 and P3T3B27 at the end of group 3, indicating that AFLP linkage group 3 was the Z (sex) chromosome. This work provides an essential basic map for constructing a denser linkage map and for mapping genes underlying agronomically important traits in the silkworm B. mori L.

Animals↗
PubMed2001

LFA-1 expression on target cells promotes human immunodeficiency virus type 1 infection and transmission.

While CD4 and the chemokine receptors are the principal receptors for human immunodeficiency virus (HIV), other cellular proteins, such as LFA-1, are also involved in HIV infection. LFA-1 and its ligands, ICAM-1, ICAM-2, and ICAM-3, can be expressed on the cells infected by HIV, as well as on the HIV virions themselves. To examine the role of LFA-1 expressed on target cells in HIV infection, Jurkat-derived Jbeta2.7 T-cell lines that express either wild-type LFA-1, a constitutively active mutant LFA-1, or no LFA-1 were used. The presence of wild-type LFA-1 enhanced the initial processes of HIV infection, as well as the subsequent replication and transmission from cell to cell. In contrast, the constitutively active LFA-1 mutant failed to promote virus replication and spread, even though this mutant could help HIV enter cells and establish the initial infection. This study clearly demonstrates the contribution of LFA-1 in the different stages of HIV infection. Moreover, not only is LFA-1 expression important for initial HIV-cell interaction, subsequent replication, and transmission, but its activity must also be properly regulated.

Cell Adhesion↗
PubMed2001

Mechanism of temporal gradients in shear-induced ERK1/2 activation and proliferation in endothelial cells.

The aim of the current study was to investigate the intracellular signaling cascade that leads to temporal gradients in shear (TGS)-induced endothelial cell proliferation, with a focus on the involvement of extracellular signal-regulated kinases 1 and 2 (ERK1/2). With the use of well-defined pulsatile, impulse, step, and ramp laminar flow profiles, we found that TGS (impulse flow and pulsatile flow) induced an enhanced and sustained (>30 min) phosphorylation of ERK1/2 relative to step flow (which contains a step increase in shear followed by steady shear), whereas steady shear (ramp flow) alone downregulated activated ERK1/2. Nitric oxide (NO) was found to mediate both the stimulatory effect of TGS and the inhibitory effect of steady shear on endothelial ERK1/2 phosphorylation. Reactive oxygen species (ROS) were also demonstrated to be associated with TGS-induced ERK1/2 phosphorylation. Both G(q/11) and G(i3) were necessary for the activation of ERK1/2 by TGS. Finally, the TGS-induced endothelial proliferative response was abolished by ERK1/2 inhibition. Our study demonstrated the essential role of G proteins, NO, and ROS in TGS-dependent ERK1/2 activation and proliferative response in vascular endothelial cells.

Cell Division↗
PubMed2001

Biological monitoring survey of organophosphorus pesticide exposure among pre-school children in the Seattle metropolitan area.

In this study we assessed organophosphorus (OP) pesticide exposure among children living in two Seattle metropolitan area communities by measuring urinary metabolites, and identified possible exposure risk factors through a parental interview. We recruited children in clinic and outpatient waiting rooms. We obtained spot urine samples in the spring and fall of 1998 from 110 children ages 2-5 years, from 96 households. We analyzed urine samples for six dialkylphosphate (DAP) compounds, the common metabolites of the OP pesticides. Through parental interviews we gathered demographic and residential pesticide use data. At least one of the DAP metabolites was measured in 99% of the children, and the two predominant metabolites (DMTP and DETP) were measured in 70-75% of the children. We found no significant differences in DAP concentrations related to season, community, sex, age, family income, or housing type. Median concentrations of dimethyl and diethyl DAPs were 0.11 and 0.04 micromol/L, respectively (all children). Concentrations were significantly higher in children whose parents reported pesticide use in the garden (0.19 vs. 0.09 micromol/L for dimethyl metabolites, p = 0.05; 0.04 vs. 0.03 micromol/L for diethyl metabolites, p = 0.02), but were not different based on reported pet treatment or indoor residential use. Nearly all children in this study had measurable levels of OP pesticide metabolites. Some of this exposure was likely due to diet. Garden pesticide use was associated with elevated metabolite levels. It is unlikely that these exposure levels would cause acute intoxication, but the long-term health effects of such exposures are unknown. We recommend that OP pesticide use be avoided in areas where children are likely to play.

Child, Preschool↗
PubMed2001

Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes.

We studied the effects of acetonitrile, dimethyl sulfoxide (DMSO), and methanol (MeOH) in human hepatocytes on cytochrome P450 (CYP) and phase II conjugation activities: phenacetin O-deethylation (CYP1A2), coumarin 7-hydroxylation (CYP2A6), tolbutamide 4-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), testosterone 6beta-hydroxylation (CYP3A4), and umbelliferone glucuronidation and sulfation. The solvents were evaluated at concentrations (v/v) of 0.1, 1, and 2%. Previously cryopreserved human hepatocytes pooled from multiple donors were used as suspension cultures in this study. DMSO was found to inhibit CYP2C9 and CYP2C19, CYP2E1, and CYP3A4 in a concentration-dependent manner. At 2% DMSO, the activities for the four isoforms were approximately 40% (CYP2C9), 23% (CYP2C19), and 11% (CYP2E1) of that observed for 0.1% acetonitrile and 45% (CYP3A4) of that observed for 1% acetonitrile. No apparent inhibitory effects were observed for the other activities evaluated. Methanol was found to inhibit CYP2C9 and CYP2E1 activities, but to a lesser extent than DMSO. Acetonitrile had no apparent effects on any of the on any of the activities evaluated. These findings should be considered when choosing an organic solvent for metabolism studies with human hepatocytes.

Acetonitriles↗
PubMed2001

[Study on the mode of inheritance for familial polycystic ovary syndrome].

OBJECTIVE: To investigate the mode of inheritance of polycystic ovary syndrome(PCOS). METHODS: The first female relatives with irregular cycle and the first male relatives with premature balding in each nuclear family were designated the affected. Their prevalence rates in families were respectively calculated. Analyses of segregation ratio were carried out among 139 nuclear families with PCOS by the methods of simple segregation and complex segregation of genetic epidemiology, respectively. RESULTS: The prevalence rates of irregular cycle among mothers and sisters with PCOS were 37.4% and 33.1% respectively, and the prevalence rates of premature balding among fathers and brothers of patients were 19.4% and 6.5%, respectively. The simple segregation analysis indicated that the segregation ratio of PCOS trait in siblings was 0.3023, the complex segregation analysis indicated that it fitted in with the inheritance model of co-dominant disorder with full penetrance and sporadic cases. The frequency of homozygote of disease gene in population was 0.046. CONCLUSION: PCOS presents the mode of co-dominant inheritance with complete penetrance.

Female↗
PubMed2000

Laser flash photolysis evidence for styryl radical cation cyclization in the SET-induced photorearrangement of a p-methoxy-substituted 2-phenylallyl phosphite.

The SET-induced photorearrangement of dimethyl 2-(4-methoxyphenyl)allyl phosphite, 9 (UV light, uranium glass filter, 9,10-dicyanoanthracene (DCA), biphenyl), gives phosphonate 12 in 83% isolated yield. Laser flash irradiation at 355 nm of oxygen saturated solutions of phosphite 9 containing DCA and biphenyl generates the transient UV spectrum of the biphenyl radical cation that is quenched by electron transfer from phosphite 9 (k(q) = 8.9 x 10(9) M(-1) s(-1) at 20 degrees C) to form the 4-methoxystyryl cation 10. The UV spectrum of 10 decays by a measured first-order rate constant of 8.0 x 10(6) s(-1), presumably to generate the cyclic distonic radical cation 11. Intermediate 10 was further characterized by measurement of the second-order rate constants for its reaction with azide, chloride, and bromide ions and with the neutral nucleophile trimethyl phosphite. This study provides the first spectroscopic evidence regarding the proposed mechanism (Schemes 1 and 2) for the SET-induced photorearrangements of dimethyl 2-arylallyl phosphites to the corresponding 2-arylallylphosphonates. Moreover, absolute rate constants for the intramolecular trapping of alkene radical cations have seldom been measured. The removal of the electron from the styryl moiety of phosphite 9, rather than from phosphorus, and the detectability of 10 arise from the stabilizing effect of the 4-methoxy substituent. These results, however, do not allow conclusions to be made concerning the site of removal of an electron in the SET-induced photorearrangement of dimethyl 2-phenylallyl phosphite 1 to phosphonate 6.

Allyl Compounds↗
PubMed2000

The top of the inserted-like domain of the integrin lymphocyte function-associated antigen-1 beta subunit contacts the alpha subunit beta -propeller domain near beta-sheet 3.

We find that monoclonal antibody YTA-1 recognizes an epitope formed by a combination of the integrin alpha(L) and beta(2) subunits of LFA-1. Using human/mouse chimeras of the alpha(L) and beta(2) subunits, we determined that YTA-1 binds to the predicted inserted (I)-like domain of the beta(2) subunit and the predicted beta-propeller domain of the alpha(L) subunit. Substitution into mouse LFA-1 of human residues Ser(302) and Arg(303) of the beta(2) subunit and Pro(78), Thr(79), Asp(80), Ile(365), and Asn(367) of the alpha(L) subunit is sufficient to completely reconstitute YTA-1 reactivity. Antibodies that bind to epitopes that are nearby in models of the I-like and beta-propeller domains compete with YTA-1 monoclonal antibody for binding. The predicted beta-propeller domain of integrin alpha subunits contains seven beta-sheets arranged like blades of a propeller around a pseudosymmetry axis. The antigenic residues cluster on the bottom of this domain in the 1-2 loop of blade 2, and on the side of the domain in beta-strand 4 of blade 3. The I domain is inserted between these blades on the top of the beta-propeller domain. The antigenic residues in the beta subunit localize to the top of the I-like domain near the putative Mg(2+) ion binding site. Thus, the I-like domain contacts the bottom or side of the beta-propeller domain near beta-sheets 2 and 3. YTA-1 preferentially reacts with activated LFA-1 and is a function-blocking antibody, suggesting that conformational movements occur near the interface it defines between the LFA-1 alpha and beta subunits.

Amino Acid Sequence↗
PubMed2000

Folding and function of I domain-deleted Mac-1 and lymphocyte function-associated antigen-1.

In those integrins that contain it, the I domain is a major ligand recognition site. The I domain is inserted between beta-sheets 2 and 3 of the predicted beta-propeller domain of the integrin alpha subunit. We deleted the I domain from the integrin alpha(M) and alpha(L) subunits to give I-less Mac-1 and lymphocyte function-associated antigen-1 (LFA-1), respectively. The I-less alpha(M) and alpha(L) subunits were expressed in association with the wild-type beta(2) subunit on the surface of transfected cells and bound to all the monoclonal antibodies mapped to the putative beta-propeller and C-terminal regions of the alpha(M) and alpha(L) subunits, suggesting that the folding of these domains is independent of the I domain. I-less Mac-1 bound to the ligands iC3b and factor X, but this binding was reduced compared with wild-type Mac-1. In contrast, I-less Mac-1 did not bind to fibrinogen or denatured bovine serum albumin. Binding to iC3b and factor X by I-less Mac-1 was inhibited by the function-blocking antibody CBRM1/32, which binds to the beta-propeller domain of the alpha(M) subunit. I-less LFA-1 did not bind its ligands intercellular adhesion molecule-1 and -3. Thus, the I domain is not essential for the folding, heterodimer formation, and surface expression of Mac-1 and LFA-1 and is required for binding to some ligands, but not others.

Animals↗
PubMed2000

Reaction of reducing hydroxyl radical adducts of pyrimidine nucleotides with riboflavin and flavin adenine dinucleotide (FAD) via electron transfer: a pulse radiolysis study.

Using the techniques of pulse radiolysis with time-resolved spectrophotometric detection, it has been demonstrated that the interaction of reducing OH radical adducts of dCMP, TMP and UMP with riboflavin (RF) and flavin adenine dinucleotide (FAD) does proceed via an electron transfer reaction. From buildup kinetics of radical species, the rate constants of electron transfer from reducing OH adducts of pyrimidines to RF and FAD have been determined, respectively. It could be deduced that RF and FAD would reduce the probability of repair of the damaged DNA in the presence of enzymes and antioxidants, accordingly RF and FAD might have a radiosensitization effect on DNA damage.

DNA↗
PubMed2000

Caspase-mediated degradation of AMPA receptor subunits: a mechanism for preventing excitotoxic necrosis and ensuring apoptosis.

Activation of ionotropic glutamate receptors of the AMPA and NMDA subtypes likely contributes to neuronal injury and death in various neurodegenerative disorders. Excitotoxicity can manifest as either apoptosis or necrosis, but the mechanisms that determine the mode of cell death are not known. We now report that levels of AMPA receptor subunits GluR-1 and GluR-4 are rapidly decreased in cultured rat hippocampal neurons undergoing apoptosis in response to withdrawal of trophic support (WTS), whereas levels of NMDA receptor subunits NR1, NR2A, and NR2B are unchanged. Exposure of isolated synaptosomal membranes to "apoptotic" cytosolic extracts resulted in rapid degradation of AMPA receptor subunits. Treatment of cells and synaptosomal membranes with the caspase inhibitors prevented degradation of AMPA receptor subunits, demonstrating a requirement for caspases in the process. Calcium responses to AMPA receptor activation were reduced after withdrawal of trophic support and enhanced after treatment with caspase inhibitors. Vulnerability of neurons to excitotoxic necrosis was decreased after withdrawal of trophic support and potentiated by treatment with caspase inhibitors. Our data indicate that caspase-mediated degradation of AMPA receptor subunits occurs during early periods of cell stress and may serve to ensure apoptosis by preventing excitotoxic necrosis.

Amino Acid Chloromethyl Ketones↗
PubMed2000

GM1 enhances the association of neuron-specific MAP2 with actin in MAP2-transfected 3T3 cells.

The ganglioside GM1 is a glycosphingolipid which enhances process formation of several neuronal lines and potentiates some growth factor-mediated responses. Previously we have shown that 24 h exposure of Neuro 2a cells to GM1 mobilized the neuron-specific microtubule-associated protein, MAP2, away from microtubule-rich areas to areas of neurite sprouting where MAP2 was more closely associated with the subcortical actin network. To examine the role of GM1 in fostering the shift of the association of MAP2 from tubulin to actin, NIH 3T3 cells were co-transfected with pHook-1, which expresses a surface antigen, and a construct expressing MAP2. Transfected cells were selected with magnetic beads coated with a hapten that binds to the expressed surface antigen and treated with 150 microg/ml GM1 for 18-24 h. Actin and MAP2 or tubulin and MAP2 were immunolocalized and examined with confocal microscopy. MAP2 was found throughout the cytoplasm as well as associated with actin filaments. As observed previously with Neuro 2a, GM1 treatment of transfected fibroblasts redistributed the MAP2 away from direct association with microtubules to peripheral areas where the association of MAP2 with actin was enhanced. GM1 did not induce neurite-like processes in MAP2-transfected cells. Treatment with cytochalasin B, which is reported to result in process formation, also did not induce neurite-like processes. These studies suggest that GM1's ability to mobilize MAP2 and promote its association with actin is not restricted to neurons.

3T3 Cells↗
PubMed2000

Enoximone echocardiography for predicting recovery of left ventricular dysfunction after revascularization : a novel test for detecting myocardial viability.

BACKGROUND: The possibility that enoximone, a nonglycoside, noncatechol, positive inotropic agent, in combination with 2-dimensional echocardiography may predict recovery of myocardial dysfunction after revascularization has not been yet evaluated. METHODS AND RESULTS: Forty-five patients with chronic coronary artery disease and left ventricular dysfunction underwent dobutamine (DE, 5 to 10 microg. kg(-1). min(-1)) and enoximone (EE, 1.5 mg/kg, over 10 minutes) echocardiography. Myocardial wall motion was scored from 1 (normal) to 4 (dyskinesia): an asynergic segment was considered to have contractile enhancement when the score decreased by >/=1 grade. Of 478 asynergic segments, 216 (45%) exhibited functional recovery after revascularization. Dobutamine- and enoximone-induced contractile enhancement was observed in 41% and 46% of segments, respectively. Compared with DE, EE had higher sensitivity (88% versus 79%, P<0.01) and negative predictive value (90% versus 84%, P<0.05) in predicting functional recovery. The specificity (89% versus 90%) and positive predictive value (87% for both EE and DE) were similar. Concordant interpretation of EE and DE findings was found in 85% (406 of 478) of affected segments. Prerevascularization coronary angiography showed that stenosis severity of vessels supplying areas which only improved with enoximone was significantly greater (89.9%) than that of vessels (77.7%) supplying areas that responded to both agents (P<0.02). Both dobutamine and enoximone increased heart rate (16% and 10%, respectively), whereas enoximone did not cause changes in systolic blood pressure that increased by 14% with dobutamine. CONCLUSIONS: Enoximone echocardiography provides a novel and reliable approach for the prediction of functional recovery after revascularization. Compared with dobutamine echocardiography, the test yields higher sensitivity and induces lesser hemodynamic alterations.

Adult↗
PubMed2000

Photosynthetic CO(2) assimilation, chlorophyll fluorescence and photoinhibition as affected by nitrogen deficiency in maize plants.

Effects of nitrogen deficiency on photosynthetic CO(2) assimilation, PSII photochemistry and photoinhibition were investigated in maize plants grown under natural illumination. Nitrogen-deficient plants had a significantly smaller CO(2) assimilatory capacity, but they showed little changes in the maximal efficiency of PSII photochemistry, the rate of Q(A) reduction and the heterogeneity of PSII reaction centers, suggesting that nitrogen deficiency had little effects on PSII primary photochemistry and photoinhibition even under natural illumination. However, modifications in PSII photochemistry under the steady state of photosynthesis induced by nitrogen deficiency were observed. This is reflected in decreases in the quantum yield of PSII electron transport, the efficiency of excitation energy capture by open PSII reaction centers, and the photochemical quenching coefficient and an increase in the non-photochemical quenching coefficient. These results suggest that modifications of PSII photochemistry under the steady state of photosynthesis may be a mechanism to downregulate photosynthetic electron transport so that production of ATP and NADPH would be in equilibrium with the decreased demand in the Calvin cycle in nitrogen-deficient plants. On the other hand, the nitrogen-deficient plants still exhibited increased susceptibility to photoinhibition when exposed to very high irradiance, although nitrogen deficiency induced no photoinhibition under natural illumination. Our results suggest that such increased susceptibility to photoinhibition was associated with the increased accumulation of inactivated PSII reaction centers, the decreased capacity of non-photochemical quenching, and the increased fraction of the reduction state of Q(A).

Journal Article↗
PubMed2000

Lens opacifications detected by slitlamp biomicroscopy are associated with exposure to organic nitrate explosives.

CONTEXT: Unusual cataracts (flecks) have been reported to occur at very low levels of trinitrotoluene exposure, but prevalence estimates vary widely. Cataracts have not been reported among workers in the United States exposed to organic nitrate explosives. OBJECTIVES: To determine the prevalence of unusual cataracts in a population of workers in the United States exposed to organic nitrate explosives, to determine whether associations exist with reported cataract risk factors, and to determine if other eye effects (eg, retinal hemorrhage) are associated with exposure. DESIGN: Cohort prevalence study. SETTING: A university-based ophthalmologic clinic. SUBJECTS: Sixty-one workers from an explosives plant comprised the exposed group. The comparison group consisted of 56 workers using chemicals other than organic nitrate explosives. OUTCOME MEASURES: The primary outcome measure was opacifications (flecks) of the crystalline lens, graded clinically on a scale of 0 to 4 +. Additional measures included visual acuity, applanation tonometry, and clinical evaluation using standard examination techniques. RESULTS: Sixty-three percent of the workers had anterior cortical lens opacifications in a pattern of peripheral flecks. Exposed subjects were 18 times more likely to exhibit changes than those not exposed, a statistically significant association (95% confidence interval [CI], 5.0-65.0; P<.001). A statistically significant association with the duration of exposure was also found. CONCLUSIONS: Asymptomatic, low-grade cataracts (flecks) were identified in 63% of the workers exposed to pentolite. No other eye effects were found to be associated with exposure. Cataracts were not associated with other known risk factors, but were associated with the duration of exposure. Biomicroscopy is widely available and useful for detecting changes in the asymptomatic stages.

Adult↗
PubMed2000

Pesticide exposure of children in an agricultural community: evidence of household proximity to farmland and take home exposure pathways.

Children's exposure to organophosphorus (OP) pesticides in an agricultural community in central Washington State was determined. Spot urine and hand wipe samples were collected from 109 children 9 months to 6 years of age, as were house dust samples, and wipe samples from various surfaces. Children were categorized based on parental occupation (agricultural vs nonagricultural) and on household proximity to pesticide-treated orchards. Median house dust concentrations of dimethyl OP pesticides in homes of agricultural families were seven times higher than those of reference families (1. 92 vs 0.27 microg/g; P<0.001). Median pesticide metabolite concentrations in agricultural children were five times higher than those in reference children (0.05 vs 0.01 microg/ml; P=0.09). Median pesticide concentrations in housedust (P=0.01) and metabolite concentrations in urine (P=0.01) from agricultural families were significantly higher in the children living near treated orchards (within 200 ft or 60 m) than those living more distant. Ten of 61 agricultural children had detectable OP pesticide levles on their hands, whereas none of the reference children had detectable levels. These findings indicate that children living with parents who work with agricultural pesticides, or who live in proximity to pesticide-treated farmland, have higher exposures than do other children living in the same community

Agriculture↗
PubMed2000

Open-loop and closed-loop optokinetic nystagmus (OKN) in myasthenia gravis and nonmyasthenic subjects.

Optokinetic nystagmus (OKN) eye movements of myasthenia gravis (MG) and nonmyasthenic ocular palsies, and normal subjects were examined under closed-loop and open-loop conditions. The open-loop OKN condition was achieved by adding the signal of eye-movement velocity of OKN to the computer-generated signal controlling the stimulus grating moving. The OKN was recorded by means of electromagnetic search scleral coil technique. In MG patients, the open-loop gains of OKN increased significantly after the intramuscular injection of an acetylcholinesterase inhibitor, neostigmine, while the closed-loop OKN gains were not significantly changed. Both the closed-loop and open-loop OKN gains of normal subjects and nonmyasthenic patients were not increased for the administration of neostigmine. The experimental results indicated that the open-loop OKN gain could be sensitive to reflect the changes of the function of neuromuscular junction in MG patients.

Adolescent↗