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Biomedical subjects

P Lu

Publications and source records attributed to P Lu.

At least 127 records · Page 7Linked to original sources

Dietary beta-alanine results in taurine depletion and cerebellar damage in adult cats.

We have used the taurine analogue, beta-alanine, to perturb the taurine concentrations in taurine-supplemented and taurine-deprived adult cats. By using 5% beta-alanine in the drinking water for 20 weeks, both groups of cats had greatly reduced brain taurine concentrations. Taurine-supplemented cat brain accumulated relatively small amounts of beta-alanine whereas taurine-deprived cats accumulated large amounts of beta-alanine. The cerebellum of cats treated with beta-alanine had a number of pathological changes compared with similar cats drinking water alone. The changes were more severe in the taurine-deprived cats, and included reduced numbers of granule and Purkinje cells, with many of those remaining appearing pyknotic and dying. Long swollen fibers were seen in the white matter, resembling Rosenthal fibers described in some human cerebellar diseases. There was also prominent gliosis. Using antibodies to beta-alanine and taurine, beta-alanine was localized in Purkinje cell soma and dendrites, in Golgi II cells, and in some granule cells, especially in taurine-deprived cats treated with beta-alanine. Taurine appears to have been virtually eliminated from Purkinje and granule cells, and concentrated in Golgi II cells and glia. We conclude that beta-alanine is responsible for these neurotoxic pathological changes.

Administration, Oral↗

H. polygyrus: B7-independence of the secondary type 2 response.

The gastrointestinal nematode parasite, Heligmosomoides polygyrus, has been used extensively in experimental studies of host immunity. The pronounced type 2 primary immune response to H. polygyrus is associated with elevated CD4+, TCR-alpha/beta + T cell IL-4 production and elevated serum IgE levels that are blocked by inhibiting CD28/ CTLA4-B7 interactions following in vivo administration of the chimeric fusion protein, CTLA4Ig. In the present study, we have examined the in vivo effects of blocking CTLA4Ig ligands on the secondary type 2 mucosal host protective immune response to this parasite. Our results show that although CD4+, TCR-alpha/beta + cells remain the primary source of elevated IL-4 during the secondary response, the protective immune response and the effector cell activity associated with it is B7-independent as CTLA4Ig administration at the time of challenge does not block (1) elevations in T cell IL-4 gene expression or protein secretion; (2) elevations in serum IgE levels, mucosal mastocytosis, or eosinophilia; or (3) host protection, as measured by adult worm burden and fecundity. These findings suggest that memory T helper cells do not require CD28-B7 interactions for their activation to effector cells that can mediate a host protective type 2 immune response.

Abatacept↗

Biodistribution and autoradiographic localization of I-125--labeled synthetic Peptide in aortic atherosclerosis in cholesterol-fed rabbits.

I-125 labeled SP4 is a synthetic oligopeptide derived from apolipoprotein B of low-density lipoprotein that has been shown to localized in atherosclerotic plaques in experimental animals. However, its biodistribution and mechanism of localization need to be further elucidated. Twenty-four cholesterol-fed (CF) and 20 normal (NL) New Zealand White rabbits were injected with I-125-SP4 and killed 15 to 30 min (6 NL; 6 CF) or 2 h (14 NL; 18 CF) later. We obtained aortic autoradiograms and activity concentrations (% injected dose/gm) in aortic segments and other tissues. The uptake of I-125-SP4 was higher in CF than in NL rabbits in all aortic segments (p < 0.05). I-125-SP4 was cleared rapidly in both CF and NL rabbits with 60 to 70% of the injected dose cleared from the blood by 1 h. No statistically significant differences in radiotracer biodistribution were observed between NL and CF rabbits although activity tended to be higher in the liver, gallbladder, and intestine in NL rabbits and in the kidney and spleen in CF rabbits. Silver grains were distributed mainly on foam cells of the fatty streaks in aortic microautoradiograms from two additional rabbits that had been injected with I-125-SP4. There were 23,518 plus minus 15,878 (SD) grains/mm(2) in fatty plaques but only 14,669 plus minus 11,035 grains/mm(2) in media muscle (p < 0.0001 [9 sections, 17 areas evaluated] in an atherosclerotic animal) in injected animals and 13,439 plus minus 5,565 grains/mm(2) in media muscle (two sections, four areas) in the normal control animals (NS versus media of atherosclerotic animal). I-125-SP4 specifically localizes in aortic atherosclerotic plaques in CF rabbits. There is no significant difference in tissue distribution between normal and CF rabbits except in the aorta. Preliminarily, it appears that the site of tracer uptake is on foam cells and this suggests the possibility of relative specificity for fatty plaque.

Journal Article↗

Identification of a meristem L1 layer-specific gene in Arabidopsis that is expressed during embryonic pattern formation and defines a new class of homeobox genes.

Homeobox genes are master regulatory genes that specify the body plan and control development of many eukaryotic organisms, including plants. We isolated and characterized a cDNA designated ATML1 (for Arabidopsis thaliana meristem L1 layer) that encodes a novel homeodomain protein. The ATML1 protein shares high sequence homology inside and outside of the homeodomain with both the Phalaenopsis O39 and the Arabidopsis GLABRA2 (GL2) homeodomain proteins, which together define a new class of plant homeodomain-containing proteins, designated HD-GL2. The ATML1 gene was first expressed in the apical cell after the first asymmetric division of the zygote and continued to be expressed in all proembryo cells until the eight-cell stage. In the 16-cell proembryo, the ATML1 gene showed a distinct pattern of expression, with its mRNA becoming restricted to the protoderm. In the torpedo stage of embryo development, ATML1 mRNA disappeared altogether but reappeared later only in the L1 layer of the shoot apical meristem in the mature embryo. After germination, this L1 layer-specific pattern of expression was maintained in the vegetative shoot apical meristem, inflorescence, and floral meristems, as well as in the young floral organ primordia. Finally, ATML1 mRNA accumulated in the protoderm of the ovule primordia and integuments and gradually became restricted in its expression to the endothelium surrounding the embryo sac. We propose that ATML1 may be involved in setting up morphogenetic boundaries of positional information necessary for controlling cell specification and pattern formation. In addition, ATML1 provides an early molecular marker for the establishment of both apical-basal and radial patterns during plant embryogenesis.

Amino Acid Sequence↗

HIV infection and AIDS in China, 1985 through 1994.

OBJECTIVES: This paper analyzes data on the distribution of and risk factors for the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection in China. METHODS: Ten years of data on persons tested for HIV infection and AIDS and the proportion who tested positive were analyzed against the background of China's population count. The Chinese- and English-language literature on HIV and AIDS from 1985 through 1995 was also reviewed. RESULTS: Overall, more males than females had HIV infection. Intravenous drug use was the primary source of transmission, followed by heterosexual contacts. Only a small number of the persons tested were homosexual, but their proportion of HIV seropositivity ranked third to that of drug users; that of general hospital patients ranked fourth. CONCLUSIONS: HIV infection and AIDS in China began as a highly regionalized and largely rural problem in Yunnan Province. However, HIV infection and AIDS have become an emerging urban problem. HIV seropositivity is low among several groups thought to have an elevated risk.

Acquired Immunodeficiency Syndrome↗

A study of platelet specific antibody (anti-Sib(a)).

OBJECTIVE: To screen and analyse the platelet-specific alloantibody form the sera of patients who received multiple platelet transfusions or experienced side effects after platelet transfusions. METHODS: 156 patients, who received multiple platelet transfusion or experienced side effects after platelet transfusion, were collected from hospitals in Shanghai. The simplified sensitized erythrocyte platelet serology assay (SEPSA) was used to screen the platelet antibodies and the identification of specificities of the platelet alloantibodies was performed with a platelet panel of known antigens and absorption tests. RESULTS: Seventy-four sera were found positive. Among them 59 sera (47.4%) contained HLA antibodies, two sera (2.7%) platelet-specific antibodies, and 13 sera both HLA and platelet-specific antibodies. One of 2 sera containing platelet-specific alloantibody, the serum Zhu, was confirmed to have a monospecific platelet-specific alloantibody, the anti-Sib(a) (HPA-2b). CONCLUSIONS: We report the first case of anti-Sib(a) in Chinese Han population. The antigen frequency of Sib(a) is considered as one of the most important antibodies which will cause the platelet transfusion refractoriness in China.

Antigens, Human Platelet↗

[The application of the expert system in prosthedontics].

In this study, we developed an expert system for designing of frame work of Removable Partial Denture by the method of Artificial Intelligence. Both of Quick Basic and Tuber C language are used in this program. This system consider more other relative factors in removable partial denture designing except the amount and position of missing teeth. Base the idea of multy-layer knowledge we divide the process RPD designing into different layers according to their logical relationships. So, this system could imitate better the expert of prosthedontics to do the clinical examination, diagnosis, treatment plan and denture designing. There are 11 modules in this system totally. They are used to accomplish the case register, first visit examination, treatment plan, abutment examination, denture designing, biomechanic analysis of abutment, reference, explanation and etc. We used this system for 20 partial edentulous patients and compared the results with the designing plans of expert of prosthedontics, the rate of conformity is 83.6%.

Denture, Partial, Removable↗

[The comparative study of the macular light threshold in the normal and low visual acuity people].

PURPOSE: To test the macular light threshold (MLT) and the change of macular light sensitivity (MLS) in the normal and low visual acuity people. METHODS: MLT of 93 eyes of the normal and 76 eyes of low visual acuity people was measured with macular threshold test of Humphrey Field Analyzer-640. RESULTS: 1. MLT increases with age, there is a negative correlation between MLS and age 2. MLT of low visual acuity people is significantly higher than that of the normal visual acuity people in the same age group; 3. No significant difference of MLT was found in the four quadrants of visual field in the same age group; 4. No significant difference of MLT was found between male and female. CONCLUSIONS: MLS of the normal visual acuity people is superior to that of the low visual acuity people; MLS decreases with age.

Adult↗

Heteroatom substitution shifts regioselectivity of lauric acid metabolism from omega-hydroxylation to (omega-1)-oxidation.

In contrast to several isoforms of cytochrome P450 (including 1A1, 1A2, 2B1, 2C2, 2C6 and 2E1), cytochrome P450 4A1 and a fusion protein derived from it, show a strong preference for hydroxylation of lauric acid (C12) at the less chemically reactive omega-CH3 group instead of the more reactive (omega-1)-CH2 group. We have explored the interplay of steric effects on substrate binding vs chemical reactivity at various substrate loci in determining the striking difference in regioselectivity of CYP2B1 and a 4A1-derived fusion protein, through studies with heteroatom substituted analogs of lauric acid, i.e., 10-methoxydecanoic acid and 10-methylthiodecanoic acid. With both enzymes the former undergoes simple omega-hydroxylation (giving 10-hydroxydecanoic acid and HCHO), but the latter undergoes facile S-oxidation at the omega-1 position instead of omega-hydroxylation. The dramatic shift in the regioselectivity of the fusion protein toward the thia analog is consistent with the greater length of C-S bonds and the greater atomic radius and polarizability of sulfur lone-pair electrons within an otherwise restrictive active site.

Animals↗

Rapid genome change in synthetic polyploids of Brassica and its implications for polyploid evolution.

Although the evolutionary success of polyploidy in higher plants has been widely recognized, there is virtually no information on how polyploid genomes have evolved after their formation. In this report, we used synthetic polyploids of Brassica as a model system to study genome evolution in the early generations after polyploidization. The initial polyploids we developed were completely homozygous, and thus, no nuclear genome changes were expected in self-fertilized progenies. However, extensive genome change was detected by 89 nuclear DNA clones used as probes. Most genome changes involved loss and/or gain of parental restriction fragments and appearance of novel fragments. Genome changes occurred in each generation from F2 to F5, and the frequency of change was associated with divergence of the diploid parental genomes. Genetic divergence among the derivatives of synthetic polyploids was evident from variation in genome composition and phenotypes. Directional genome changes, possibly influenced by cytoplasmic-nuclear interactions, were observed in one pair of reciprocal synthetics. Our results demonstrate that polyploid species can generate extensive genetic diversity in a short period of time. The occurrence and impact of this process in the evolution of natural polyploids is unknown, but it may have contributed to the success and diversification of many polyploid lineages in both plants and animals.

Biological Evolution↗

Fatty acid discrimination and omega-hydroxylation by cytochrome P450 4A1 and a cytochrome P4504A1/NADPH-P450 reductase fusion protein.

The omega-hydroxylation of fatty acids by certain cytochrome P450 enzymes shows a degree of chain-length and regionspecificity which is remarkable in view of the conformational flexibility of these substrates, the strong similarity in properties among homologs, and the lack of polar groups (other than the carboxy terminus) with which to guide and strength enzyme-substrate interactions. To investigate the chemical basis for these features of omega-hydroxylation we designed and synthesized a series of lauric acid analogs and evaluated them as substrates and inhibitors of omega-hydroxylation catalyzed by cytochrome P4504A1 and a cytochrome P450 4A1/NADPH-P450 reductase fusion protein. Among n-alkanoic acids, lauric acid was found to have the optimum chain length for the fusion protein, as it does for native cytochrome P450 4A1. With both enzymes, chain shortening caused a precipitous drop in turnover while chain lengthening caused a gradual drop in turnover. The fusion protein omega-hydroxylated methyl laurate and lauryl alcohol about 1/10th as efficiently as lauric acid, but it did not hydroxylate lauramide. 10-Methoxydecanoic acid underwent O-demethylation (via omega-hydroxylation). The branched substrate 11-methyllauric acid was hydroxylated efficiently and selectively at the omega-position. In contrast, the cyclopropyl analog 11,12-methanolauric acid was not detectably hydroxylated, although it induced Type I binding spectrum and inhibited lauric acid omega-hydroxylation by 43% at equimolar concentrations. omega-(Imidazolyl)-decanoic acid induced a Type II heme-binding spectrum and was an especially potent inhibitor of lauric acid hydroxylation. Collectively these data suggest that the active site of cytochrome P450 4A1 has an elongated tubular shape of definite length (ca. 14 A) with a recognition site for polar groups (including but not limited to carboxyl) at its entrance and the (oxo)heme group at its terminus.

Cytochrome P-450 CYP4A↗

Altered GABA distribution in hamster brain is an early molecular consequence of infection by scrapie prions.

Antibodies specific for GABA, glutamate and taurine were used to study the distribution of these amino acid neurotransmitters during the progression of scrapie in hamsters. Immunohistochemical distribution of glutamate and taurine were unaffected in scrapie hamsters compared with controls, but the distribution of GABA was altered by 21 days after inoculation. We found both a greater number of neurons showing GABA-like immunoreactivity and more intense staining in those neurons in scrapie-inoculated hamster brains, particularly in the hippocampus, inferior colliculus, frontal cortex and cerebellum. The overall concentrations of aspartate, GABA, glutamate and taurine, measured in seven different brain regions by PITC-amino acid analysis, were not significantly different between normal and scrapie-affected hamsters. The subtle alteration in GABA metabolism detected in this scrapie model suggests that PrPSc interacts directly with a component of the GABA system.

Animals↗

Sucrose: a solute that accumulates in the guard-cell apoplast and guard-cell symplast of open stomata.

Stomatal conductances of Vicia faba leaves were recorded over a day. Coordinately, (a) guard cells dissected from leaflets were assayed, providing total sucrose content, and (b) guard cells dissected from rinsed epidermes were also assayed, providing symplastic sucrose content. Compared with that of pre-dawn samples, apoplastic sucrose content increased 4.8-5.2 x (2 experiments), reaching 1,130-1,300 fmol.guard-cell-pair-1 at midday, when conductance was highest (ca. 0.13 mol.m-2.s-1); symplastic sucrose content increased 2.5-3.5 x, reaching 350-390 fmol.guard-cell-pair-1. Thus, there is a correlation between transpiration and guard-cell sucrose content, particularly that portion localized to the apoplast. Moreover, apoplastic sucrose is apparently a source of guard-cell nutrition and, possibly, osmoticum.

Carbon Dioxide↗