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Biomedical subjects

D Lu

Publications and source records attributed to D Lu.

At least 253 records · Page 14Linked to original sources

Retrovirus-mediated transfer of an angiotensin type I receptor (AT1-R) antisense sequence decreases AT1-Rs and angiotensin II action in astroglial and neuronal cells in primary cultures from the brain.

The AT1-R has been implicated in many cellular and physiological actions of angiotensin II (AII) in the brain. A retrovirus vector (LNSV) containing an AT1B-R antisense sequence (AT1B-AS) (termed LNSV-AT1B-AS) was constructed and used to determine the feasibility of using viral-mediated gene transfer to control AT1-Rs and AII actions in astroglial and neuronal cells in primary cultures from rat brain. Briefly, a 1.26-kb antisense sequence corresponding to nt -132 to +1128 of AT1-R cDNA was cloned into the LNSV vector, the vector was transfected into PA317 cells, and transfected cells were selected in G418. Incubation of brain cells with culture medium containing LNSV-AT1B-AS viral particles showed that AT1B-AS was integrated into the genome and transcribed in brain cells. This was associated with a significant decrease in AT1-Rs and in the AII-stimulated increase of c-fos mRNA, a measure of AT1-R function. These observations show that the AT1B-AS gene can be transferred into astroglial cells in culture by LNSV and that such a transfer inhibits AT1-Rs and the AII stimulation of cellular activities. In addition, the usefulness of this approach to study AII-dependent pathophysiology in primary neuronal cultures from brain, in particular, is established.

Angiotensin I↗

An isochromosome of the long arm of chromosome 18 in a patient with myelodysplastic syndrome with myelofibrosis.

A case of myelodysplastic syndrome (MDS) with myelofibrosis and i(18q) is reported. The patient, a 29-year-old Chinese man, was noted to be anemic over a 10-year period. Recently, his spleen became progressively massive and bone marrow aspirates yielded "dry taps" on several occasions. Hematologic investigation disclosed pancytopenia, numerous nucleated red cells, and slightly increased myeloblasts (8%) in the peripheral blood. Bone marrow aspirate and biopsy revealed hypercellular marrow, trilineage dysplasia, and significant reticulin fibrosis, but without collagen formation. Bone marrow karyotypic analysis with R-banding showed an isochromosome 18q as a sole abnormality in 20 of 24 metaphases analysed. The patient died of severe anemia and bleeding due to bone marrow failure. We believe that i(18q) and myelofibrosis may be related to his poor prognosis.

Adult↗

A matched filter echo summation technique for MRI.

A technique is presented to increase the signal-to-noise ratio (SNR) in two-dimensional (2D), phase-encoded imaging at low SNR. The essence of this technique is to combine multiple echoes in the time domain. As analyzed in the paper, phase discrepancies exist among different echoes and may deteriorate the combined echo. In particular, extraneous phase shifts can be created if unshielded gradient coils are used. To overcome these phase discrepancies, a matched filter was derived from the k = 0 component of image. This matched filter has the same phase discrepancies among its echoes as the imaging signal and its magnitude decays with an average T2. In the echo summation with the matched filter, the phase of the matched filter was subtracted from the imaging signal and the magnitude of the matched filter was used as the weighting function. We have shown that this matched filter echo summation technique has better SNR than the case of 2D, phase-encoded imaging in both simulation and experiment. The SNR improvement is up to 60% in a phantom experiment. This technique is mostly useful in low SNR imaging that requires long imaging time, such as spectroscopic imaging and 19F imaging.

Humans↗

Magnetic resonance spectroscopy in childhood AIDS encephalopathy.

Twenty-five children with acquired immunodeficiency syndrome (AIDS) underwent cranial magnetic resonance imaging and proton magnetic resonance spectroscopy. Patients were divided into 2 groups based on clinical parameters: encephalopathy and nonencephalopathy. N-acetyl aspartate/creatine ratios were compared between the 2 groups and to control data. Spectra were obtained for 2 volumes of interest: the basal ganglia region and the white matter. The mean basal ganglia region ratio for the AIDS encephalopathy patients (n = 8) was 1.12 and the ratio for the AIDS nonencephalopathy patients (n = 17) was 1.48. The ratio for the 9 controls was 1.57. The encephalopathy group had a significantly lower ratio than both the control (P < .001) and the AIDS nonencephalopathy group (P < .002). The mean white matter ratio for the encephalopathy group (n = 8) was 1.47 and for the AIDS nonencephalopathy group (n = 13) was 1.82 with a control (n = 6) ratio of 1.82. The encephalopathy patients had a lower white matter ratio than the nonencephalopathy (P < .05) patients but the ratio was not different than controls (P < .11). It is concluded that N-acetyl aspartate/creatine ratios are reduced in childhood AIDS encephalopathy and proton magnetic resonance spectroscopy may be helpful in defining brain human immunodeficiency virus-1 infection. However, further longitudinal studies are necessary to determine the sensitivity and specificity of this technique.

AIDS Dementia Complex↗

Glycosphingolipid fatty acid arrangement in phospholipid bilayers: cholesterol effects.

Deuterium wide line NMR spectroscopy was used to study cholesterol effects on the ceramide portions of two glycosphingolipids (GSLs) distributed as minor components in fluid membranes. The common existence of very long fatty acids on GSLs was taken into account by including one glycolipid species with fatty acid chain length matching that of the host matrix, and one longer by 6 carbons. N-stearoyl and N-lignoceroyl galactosyl ceramide with perdeuterated fatty acid (18:0[d35] GalCer and 24:0[d47] GalCer) were prepared by partial synthesis. They were dispersed in bilayer membranes having the 18-carbon-fatty-acid phospholipid, 1-stearoyl-2-oleoyl-phosphatidylcholine (SOPC), as major component. Glycolipid fatty acid chain behavior and arrangement were analyzed using order profiles derived from their 2H-NMR spectra. Cholesterol effects on order parameter profiles for 18:0[d35] GalCer, with chain length equal to that of the host matrix, followed the pattern known for acyl chains of phospholipids. The presence of sterol led to restriction of trans/gauche isomerization along the length of the chain, with the largest absolute increase in order parameters being toward the surface, but somewhat greater relative effect just below the "plateau" region. In cholesterol-containing membranes, order parameter profiles for the long chain species, 24:0[d47] GalCer, showed a characteristic secondary "plateau" associated with carbon atoms C14 to C23, a feature also present in SOPC bilayers without cholesterol and in pure hydrated 24:0[d47] GalCer. Cholesterol-induced ordering effects on the long chain glycolipid were similar to those described for the shorter chain species, but were minimal at the methyl terminus. Within a given membrane,SCD profiles for 1 8:O[d3] GalCer and 24:0[d47] GalCer were quantitatively similar to a membrane depth of C13 to C14. SCD values at C16 and C17 were about 15% and 28% higher, respectively, for the long chain GSL than for its short chain analogue inSOPC/cholesterol (compared to 21 and 31%, respectively, in membranes without cholesterol). Nitroxide spin labels attached rigidly to C16 of the long chain glycolipid gave EPR order parameters that were twice as high as for the same spin label at C16 on the shorter chain glycolipid in both matrices. It would appear that the above factors impose a tendency for the "extra" portion of the 24-carbon chain to cross the bilayer midplane where it may interact with terminal portions of acyl chains in the opposing monolayer; however, steric constraints, and probably collision events associated with lateral diffusion, induce wide orientation fluctuations in the segment involved.

Animals↗

Smoothed acyl chain orientational order parameter profiles in dimyristoylphosphatidylcholine-distearoylphosphatidylcholine mixtures: a 2H-NMR study.

The accommodation of chain-length mismatch in liquid crystal phase bilayers was examined by using deuterium nuclear magnetic resonance to obtain smoothed orientational order parameter profiles for acyl chains of both components in binary lipid mixture bilayers. Mixtures of dimyristoylphosphatidylcholine (DMPC) and distearoylphosphatidylcholine (DSPC) covering a range of compositions were prepared with either DSPC acyl chains or DMPC acyl chains perdeuterated. Orientational order parameters in the plateau regions of the smoothed profiles for both components were found to increase smoothly with increasing DSPC concentration. The orientational order parameters in the DSPC-smoothed profile were found to be slightly higher than corresponding values for DMPC over a wide range of bilayer composition. The shapes of the smoothed profiles for both components were found to be sensitive to bilayer composition. At low DSPC concentration, DSPC methylene deuterons near the bilayer center display a secondary plateau at low orientational order. At high DSPC concentration, the plateau of the DMPC-smoothed profile is stretched slightly. The concentration dependence of the smoothed profiles at low DSPC concentration appears to be consistent with a picture in which the last few segments of the DSPC chain cross the bilayer midplane, on average, but remain very disordered.

Deuterium↗

Biochemical prototype for familial thrombosis. A study combining a functional protein C mutation and factor V Leiden.

Resistance to activated protein C (APC) is associated with a single amino acid substitution in factor V (Arg506-->Gln, factor V Leiden) that results in delayed inactivation of the molecule by APC. The mutation is present in 20% of patients with a first episode of deep venous thrombosis. Arterial and venous thromboses are also associated with the type II protein C deficiency (protein CVermont). In protein CVermont, the substitution Glu20-->Ala alone (rPC gamma 20A) is responsible for the defective anticoagulant properties of PCVermont. It was recently established that a thrombotic episode occurred in 73% of family members who are heterozygous for both a functional protein C gene mutation and the factor V Leiden mutation. We evaluated the molecular defect that would accrue in the combined deficiency state of factor VR506Q/VaR506Q and rAPC gamma 20A using recombinant APC and natural purified factor VR506Q from patients homozygous for the Arg506-->Gln substitution. While wild-type recombinant APC (rAPC) slowly cleaves and inactivates factor VR506Q and factor VaR506Q, minimal cleavage of membrane-bound factor VR506Q and VaR506Q by rAPC gamma 20A at Arg306 and Arg679 occurs, and no loss in cofactor activity is observed. Our data demonstrate that rAPC gamma 20A cannot inactivate either factor VR506Q or factor VaR506Q at biologically relevant rates because of impaired cleavage at Arg306 and Arg679.(ABSTRACT TRUNCATED AT 250 WORDS)

Factor V↗

[Effects of pregnant exposure to electromagnetic field emitted by electric blankets on brain catecholamine and behavior in offspring mice].

NIH pregnant mice were exposed to electromagnetic field emitted by electric blankets with 1-1.2kV/m and 0.2-0.4microT for five hours daily during their whole gestational period. Catecholamine (CA) content in the hypothalamus of their newborn offsprings was quantitatively measured with histochemical methods, and their varied behavioral activities were determined with behavioral toxicological methods. Results showed catecholamine content in exposed offsprings decreased significantly not only seven days but also 40 days after delivery as compared with the controls (P < 0.01 and P < 0.05, respectively).

Animals↗

Interaction between intercalation type anticancer drugs and DNA studied by ultraviolet resonance Raman spectroscopy.

The interaction of typical intercalation type anticancer drugs, adriamycin (ADM) and aclacinomycin (ACM), with calf thymus DNA was studied first with ultraviolet resonance Raman spectroscopy (UVRRS). The results demonstrate that the important information such as intercalation sites of drugs, the electronic interaction and the hydrogen bonds between drugs and DNA can be obtained by UVRRS. The method can also show the influence of drugs on DNA conformation and hydrogen bonds between bases of DNA.

Aclarubicin↗

Construction and high expression of retroviral vector with human clotting factor IX cDNA in vitro.

The construction of the high titer and highly expressed safety retroviral vector carrying human clotting factor IX cDNA is reported. Retroviral vectors LNCIX, LIXSN and LCIXSN, driven by hCMV, LTR and hCMV combined with LTR promoter respectively, were constructed, based on the retroviral vector LNL6, and transferred into packaging cell line PA317 with electroporation. Human clotting factor IX was detected in the cultured cells transduced with LNCIX and LIXSN but not in the cells transduced with LCIXSN. The viral titer of PA317/LNCIX was 800,000 CFU per mL. With ELISA detection, it was found that the cells transduced with this vector can express human clotting factor IX at the level of 3.3 micrograms per 10(6) cells in 24 h in human fibrosarcoma cells HT-1080 and 2.5 micrograms per 10(6) cells in 24 h in hemophilia B patients' skin fibroblast HSF cells, and more than 80% of them were biologically active. The viral titer and expression of human FIX were increased, and the construction of retroviral vector backbone was improved and the safety was guaranteed as compared to those vectors used previously. These vectors may produce a sufficient quantity of factor IX proteins to cause the phenotypic modification for hemophilia B patients.

Cells, Cultured↗

[Epidemiological investigation of Campylobacter Jejuni infection in children].

Epidemiological studies on campylobacter jejuni infection in children were carried out in Chengdu during December 1987 to October 1989. Detection rate of campylobacter in 1,092 children with diarrhea was 11.36%, with the highest in children aged 1-2 and the lowest in babies within six months. Campylobacter jejuni could be detected in young children with acute diarrhea all the year round, with a higher detection rate in the spring and summer and lower in the autumn and winter. Campylobacter jejuni could be detected in 5.09% of healthy children, with a significant difference between kindergartens due to their living conditions. Use of spectrum of drug-resistance and plasmid analysis in children of nurseries and kindergartens to study campylobacter infection suggested campylobacter jejuni infection in children could be caused by a lot of distant-associated strains with genetic homogeneity.

Age Factors↗

[Studies on mode of human infection with Echinochasmus liliputanus].

Epidemiological survey and experimental studies on the mode of human infection with Echinochasmus liliputanus were carried out in Chenqiaozhou Village, Hexian County, Anhui Province in 1992. The results showed that humans could be infected through drinking unboiled water containing E.liliputanus cercaria or eating raw fish containing the metacercaria. The infection rates of E. liliputanus were 1.5% in the inhabitants who did not drink raw water, and 20.1% in those who used to drink raw water. It was only the cercaria, not the metacercaria that was detected in the water from ponds of this village. None of the investigated inhabitants ate uncooked fish. The results indicated that drinking raw water containing E.liliputanus cercaria was a major way through which a humans were infected and eating food containing the metacercaria was a minor mode of human infection.

Animals↗

[Fine stereo structure for natural organic molecules, a preliminary study. II. Melting point influenced by structure factors].

Crystal structures of two compounds from Tripterygium wilfordii Hook f. have been determined by X-ray diffraction method. Structure factors influencing melting point of solid state have been analysed. Crystal class (or space group), recrystallization solvent, force between molecules and fine changes of molecular structures will all cause melting point changes of crystal substance.

Crystallography, X-Ray↗