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Biomedical subjects

L Xu

Publications and source records attributed to L Xu.

At least 829 records · Page 46Linked to original sources

Dietary marine lipid does not alter susceptibility of (NZBxNZW)F1 mice to pathogenic microorganisms.

Female (NZBxNZW)F1 mice were fed for one month with a diet in which the sources of fat were either melted beef tallow or fish oil, the latter regimen being associated with a marked decrease in the expression of auto-immune disease in these animals. To test whether or not this beneficial effect was associated with an increased risk of infection, animals fed each of these diets were challenged intraperitoneally with graded doses of four different classes of microorganisms: a gram positive bacillus that is an intracellular parasite (Listeria monocytogenes), an exotoxin-producing gram negative bacillus (Pseudomonas aeruginosa), a yeast (Candida albicans), and a herpes group virus (murine cytomegalovirus). There was no difference in the susceptibility of the animals fed the two different diets to any of these infections as shown by either determinations of the LD50 for each organism or by assessment of the times of survival for those animals that did succumb. We conclude that the beneficial anti-inflammatory effects of fish oil diets in these mice are not associated with an increased risk of infection with a variety of microbial agents.

Animals↗

Grafting fibroblasts genetically modified to produce L-dopa in a rat model of Parkinson disease.

Rat fibroblasts were infected with a retroviral vector containing the cDNA for rat tyrosine hydroxylase [TH; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2]. A TH-positive clone was identified by biochemical assay and immunohistochemical staining. When supplemented in vitro with pterin cofactors required for TH activity, these cells produced L-dopa and released it into the cell culture medium. Uninfected control cells and fibroblasts infected with the TH vector were grafted separately to the caudate of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. Only grafts containing TH-expressing fibroblasts were found to reduce rotational asymmetry. These results have general implications for the application of gene therapy to human neurological disease and specific implications for Parkinson disease.

Animals↗

Dietary marine lipids suppress murine autoimmune disease.

Dietary marine lipids reduce both mortality and the severity of glomerulonephritis in inbred murine strains which develop spontaneous autoimmune disease. The protective effects of marine lipids appear to be accounted for by the major n-3 fatty acids in these preparations, 20:5 and 22:6. The n-3 fatty acids in dietary fish oil are extensively incorporated into several lipid classes in the spleen of autoimmune mice, including phosphatidylinositol, phosphatidylethanolamine, plasmalogens and saturated ether-linked phospholipids as well as diacylphosphoglycerides. The effects of dietary marine lipids on autoimmune disease in experimental models are highly specific. Careful controlled trials will be required to establish the role of dietary marine lipids in the therapy of human autoimmune disease.

Animals↗

[Measurement of evoked otoacoustic emissions in normal-hearing adults].

A system for recording evoked otoacoustic emissions (EOAE) was developed based on the signal processor normally used in auditory evoked potential measurements. With this system, click-evoked otoacoustic emissions with latencies between 5-10 ms were recorded from all the 59 normal-hearing ears tested. Although EOAE thresholds ranged from -5 to 25 dB SL, 3/4 of them was with 0-10 dB SL. Ten measurements at intervals of 1 week in 4 ears showed that EOAE was quite stable. Thus, the measurement of EOAE was considered of clinical significance as an objective, sensitive and quick hearing-screening test. Its prospect in clinical applications was also discussed.

Acoustic Stimulation↗

Retrovirus vector-mediated gene transfer into hepatocytes.

The introduction and stable expression of foreign genes in mammalian hepatocytes have recently been demonstrated by several techniques, including the use of physical approaches such as direct injection of a DNA calcium phosphate precipitate, electroporation of plasmid DNA and the exposure to liposome-erythrocyte ghost complexes as well as the biological approach of infection of primary hepatocyte cultures with retrovirus vectors. Retrovirus-mediated transduction has proven to be highly advantageous in many in vitro gene transfer studies of mammalian cells, and recent results with primary rat liver cultures have begun to define the conditions under which foreign genes can be transduced into hepatocytes in vitro. Fully differentiated hepatocytes are poorly susceptible, if at all, to infection with retroviruses, a phenomenon due at least in part to the fact that cells must undergo replication in order to retroviral integration and gene expression to occur. Hepatocytes are largely resting cells, arrested in G0. Nevertheless, primary cultures of hepatocytes are known to demonstrate a partial de-differentiation in vitro and undergo several rounds of replication. During a narrow period of time early in primary culture correlated roughly with the de-differentiation, adult hepatocytes do become susceptible to efficient infection with retrovirus vectors. In infected cells, gene expression remains relatively stable for the several week duration of the primary culture. It is not known if the restriction of virus infection in hepatocytes is a function of the state of cellular differentiation, of the availability of viral receptors or of other factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Development of the chick embryo: effects of egg mass.

We asked to what extent, within a species, differences in egg mass, hence in eggshell surface area and O2 conductance, could affect the development of the avian embryo. Large (L, about 70 g) and small (S, about 55 g) fertile chicken eggs were simultaneously incubated and the embryos studied at day 18, i.e. before the onset of lung ventilation. Embryo mass and O2 consumption (VO2) (measured with a manometric technique) normalized per mass of the freshly laid egg were higher in S than in L, while no differences occurred after normalization by egg surface area (S.A.). Egg water vapour conductance, which is proportional to O2 conductance, was also found to be directly proportional to egg S.A. Hence, the mass and VO2 of the embryo are more closely related to the O2 conductance of the eggshell than to egg mass, giving support to the concept that the avian embryo's VO2 is not an invariable species characteristic, but a variable dependent on O2 availability. Hatching and viability did not differ between L and S, and the specific mass of heart and lung and their cellular (DNA) concentration were also similar between the two groups of embryos. Therefore, differentiation of tissues and organogenesis do not seem to be affected by the differences in total O2 availability determined by the differences in egg mass, while they are probably more important than total tissue mass in setting the time of hatching.

Animals↗

The in vitro evaluation of nucleoside analogues as probes for use in the noninvasive diagnosis of herpes simplex encephalitis.

1-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) and the 5-iodo (FIRU), 5-bromo (FBrRU), 5-chloro (FClRU) and 5-fluoro (FFRU) analogues of 1-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)uracil were examined in four in vitro tests designed to evaluate their potential as radiopharmaceuticals in a non-invasive diagnostic test for herpes simplex encephalitis (HSE). The tests involved, (a) cellular uptake studies--which showed that all five nucleosides are selectively trapped in rabbit kidney cells infected with herpes simplex virus, type I, which codes for its own thymidine kinase; (b) incubation studies--which showed that, in human platelets, FIAU, FIRU and FFRU are not degraded by thymidine phosphorylase (an enzyme which catalyzes the glycosidic bond cleavage of physiological nucleosides); (c) a transport study, using mouse erythrocytes--which indicated that all five nucleosides have good affinity for a NBMPR-sensitive nucleoside transporter, with inhibition constants (Ki values in the range of 0.177-0.41; and (d) determination of octanol/water partition coefficients--which (log P = -0.14 to -1.67) indicated that FIAU is the most lipophilic of the five compounds studied, and may therefore cross the blood-brain barrier most readily. We conclude from the results that FIAU is the most promising compound for further evaluation in HSE animal models. The combination of tests described in this study provide a useful screening protocol for evaluation of other nucleoside analogues of potential use in a diagnostic test for HSE.

Animals↗

Synthesis and antiviral activity of IVFRU, a potential probe for the non-invasive diagnosis of herpes simplex encephalitis.

Synthesis of (E)-5-(2-iodovinyl)-1-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)uracil (IVFRU; 4a), and its [125I] and [131I] derivatives (4b and 4c) are described. Compared with IVDU, IVFRU had comparable antiviral activity (MIC50 = 0.01-0.1 microgram/ml), and a greater ethanol/water partition coefficient; its affinity for the murine erythrocyte nucleoside transporter system was greater than that of 2'-deoxyuridine. The [125I] derivative (4b) was selectively trapped within rabbit kidney cells (27.9 and 41.2% at 4 and 24 hr, respectively) infected in vitro by thymidine kinase-positive (TK+) herpes simplex virus (HSV-1), but not within either HSV (TK-) or mock-infected cells where uptake was less than 1%. It was resistant to glycosidic bond cleavage by pyrimidine nucleoside phosphorylases, but underwent catabolism to an unidentified metabolite and iodide during in vivo plasma and urinary excretion studies in mice. We conclude that the [123I] derivative of IVFRU warrants further evaluation as a non-invasive radiopharmaceutical agent for the diagnosis of herpes simplex encephalitis (HSE), and that IVFRU warrants further evaluation as an antiviral agent.

Animals↗

Grafting genetically modified cells to the brain: possibilities for the future.

Diagnostic and therapeutic approaches to disorders of the central nervous system (CNS) are particularly difficult to develop because of the relative inaccessibility of the mammalian brain to study and chemical treatment, the complexity and interconnectedness of CNS subsystems, and the profound and continued lack of fundamental understanding of the relationship between structure and function in the CNS. Neural grafting in the CNS has recently suggested a potential approach to CNS therapy through the selective replacement of cells lost as a result of disease or damage. Independently, studies aimed at direct genetic therapy in model systems have recently begun to suggest conceptually new approaches to the treatment of several kinds of human genetic disease, especially those caused by single-gene enzyme deficiencies. We suggest that a combination of these two approaches, namely the grafting into the CNS of genetically modified cells, may provide a new approach toward the restoration of some functions in the damaged or diseased CNS. We present evidence for the feasibility of this approach, including a description of some current techniques for mammalian cell gene transfer and CNS grafting, and several possible approaches to clinical applications.

Brain↗

Space flight visual simulation.

In this paper, based on the scenes of stars seen by astronauts in their orbital flights, we have studied the mathematical model which must be constructed for CGI system to realize the space flight visual simulation. Considering such factors as the revolution and rotation of the Earth, exact date, time and site of orbital injection of the spacecraft, as well as its orbital flight and attitude motion, etc., we first defined all the instantaneous lines of sight and visual fields of astronauts in space. Then, through a series of coordinate transforms, the pictures of the scenes of stars changing with time-space were photographed one by one mathematically. In the procedure, we have designed a method of three-times "mathematical cutting." Finally, we obtained each instantaneous picture of the scenes of stars observed by astronauts through the window of the cockpit. Also, the dynamic conditions shaded by the Earth in the varying pictures of scenes of stars could be displayed.

Astronauts↗