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L Li

Publications and source records attributed to L Li.

At least 307 records · Page 17Linked to original sources
PubMed2001

Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway.

To understand how the Wnt coreceptor LRP-5 is involved in transducing the canonical Wnt signals, we identified Axin as a protein that interacts with the intracellular domain of LRP-5. LRP-5, when expressed in fibroblast cells, showed no effect on the canonical Wnt signaling pathway by itself, but acted synergistically with Wnt. In contrast, LRP-5 mutants lacking the extracellular domain functioned as constitutively active forms that bind Axin and that induce LEF-1 activation by destabilizing Axin and stabilizing beta-catenin. Addition of Wnt caused the translocation of Axin to the membrane and enhanced the interaction between Axin and LRP-5. In addition, the LRP-5 sequences involved in interactions with Axin are required for LEF-1 activation. Thus, we conclude that the binding of Axin to LRP-5 is an important part of the Wnt signal transduction pathway.

3T3 Cells↗
PubMed2001

Study of properties on non-protected room temperature phosphorescence and delayed excimer fluorescence of pyrene solution.

A strong and stable room temperature phosphorescence (RTP) and delayed excimer fluorescence signal located at 596 and 475 nm, respectively, can be induced for pyrene solution in the absence of any protective medium only use KI or TlNO3 as a heavy atom perturber (HAP) and Na2SO3 as a deoxygenator. Both lifetimes of RTP and the delayed fluorescence are in the order of X-ms and the intensities are changed with kind and amount of HAP, but the peak positions are same and there is a iso-luminescent point in the emission spectra corresponding to emission at 475 nm and at 596 nm. The optimum conditions and the effects of kind and amount of HAP and organic solvents on luminescence properties of pyrene solution were studies in detail, and the photophysical process in the presence of KI or TlNO3 for phosphorescence and delayed excimer fluorescence emission of pyrene solution was discussed.

Fluorescent Dyes↗
PubMed2001

Monoclonal antibodies as a strategy for pulmonary diseases.

Monoclonal antibodies have been used successfully to elucidate the roles of putative mediators of pulmonary disease. In particular, clinical trials with monoclonal antibodies directed against interleukin-5, IgE or CD4 yielded results that were critical in dissecting the pathophysiology of asthma; but, more importantly, fundamental changes in the discovery, manufacture and safety of monoclonal antibodies have reinforced the enormous potential of these agents in treating pulmonary diseases. An unprecedented number of monoclonal antibodies are in development for a variety of acute and chronic conditions. Moreover, whereas only two monoclonal antibodies had received regulatory approval from the United States Food and Drug Administration between 1986 and 1997, seven more have received approval since then. Indeed, monoclonal antibody therapy has come of age.

Animals↗
PubMed2001

Microtubule disruption modulates the Rho-kinase pathway in vascular smooth muscle.

Microtubules constitute one of the main cytoskeletal components in eukaryotic cells. Recent studies have shown that microtubule disruption induced significant vasoconstriction or enhanced agonist-induced contraction in vascular smooth muscle. However, the underlying mechanisms are not clear. We hypothesize that microtubule disruption may affect contractile signaling in vascular smooth muscle and lead to the enhanced contraction. The present study demonstrates that both colchicine and nocodazole induced a small but sustained contraction (4-6% P0) in rat aortic rings. This microtubule disruption-induced contraction was abolished by co-treatment with either HA 1077 or Y-27632, both of which are relatively specific Rho-kinase inhibitors. However, co-treatment with ML-9, an inhibitor of myosin light chain kinase, (MLCK) did not have a significant effect on the colchicine-induced contraction. The enhanced KCl-induced contraction due to treatment with colchicine was also blocked by inhibition of Rho-kinase, but not by inhibition of MLCK. These results indicate that microtubule disruption modulates contractile signaling in vascular smooth muscle, mainly through the Rho-kinase pathway, but not MLCK. Interestingly, the colchicine-enhanced, phenylephrine-induced contraction was not completely blocked by inhibition of Rho-kinase suggesting that other signaling pathways might also be involved.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Alternative splicing of prosystemin pre-mRNA produces two isoforms that are active as signals in the wound response pathway.

Systemin and its precursor protein, prosystemin, play an essential role in the systemic wound response pathway of tomato plants. We report here the isolation from tomato of a novel prosystemin cDNA (prosysB) that differs from the reported cDNA sequence (prosysA) by the addition of a CAG trinucleotide. Inspection of the prosystemin genomic sequence, which was mapped to the central region of chromosome 5, indicated that prosysA and prosysB transcripts are generated by an alternative splicing event that utilizes different 3' splice sites within intron 3. Quantitative RT-PCR analysis showed that prosysB transcripts accumulated to approximately twice the level of prosysA in all tissues that express the prosystemin gene. The relative abundance of the two mRNAs was unaffected by wounding or methyl jasmonate treatment, conditions that increase the level of total prosys mRNA. These findings indicate that alternative splicing of prosys pre-mRNA is a constitutive process. The amino acid sequence of prosysB is predicted to differ from that of prosysA by replacement of Arg-57 with Thr-Gly in the non-systemin portion of the protein. Over-expression of the prosysB cDNA in transgenic tomato plants conferred constitutive expression of defense genes that are regulated by wounding and systemin. We conclude that prosysB is the major prosystemin-encoding transcript in tomato, and that this isoform is active as a signal in the wound response pathway.

Acetates↗
PubMed2001

Tandem duplication mosaicism: characterization of a mosaic dup(5q) and review.

Mosaicism for tandem duplications is rare. Most patients reported had abnormal phenotypes of varying severity, depending on the chromosomal imbalance involved and the level of mosaicism. Post-zygotic unequal sister-chromatid exchange has been proposed as the main mechanism for tandem duplication mosaicism. However, previous molecular analyses have implicated both meiotic and post-zygotic origins for the duplication. We describe a newborn male who was originally diagnosed in utero with arrhythmia and tetralogy of Fallot. He had multiple dysmorphic features including telecanthus, blepharophimosis, high broad nasal bridge with a square-shaped nose, flat philtrum, thin upper lip, down-turned corners of the mouth, high-arched palate, micrognathia, asymmetric ears, and long, thin fingers and toes. Karyotyping of peripheral blood lymphocytes showed mosaicism for a tandem duplication of part of the long arm of one chromosome 5: mos46,XY,dup(5)(q13q33)[6]/46,XY[45]. Fibroblast cultures had the same mosaic karyotype with a higher frequency of the dup(5) clone: mos46,XY,dup(5)(q13q33)[9]/46,XY[21]. Fluorescence in situ hybridization analysis with a wcp5 confirmed the chromosome 5 origin of the additional material. Parental karyotypes were normal indicating a de novo origin of the dup(5) in the proband. Molecular analyses of chromosome 5 sequence-tagged-site (STS) markers in our family were consistent with a post-zygotic origin for the duplication. Therefore, mosaicism for tandem duplications can arise both through meiotic or mitotic errors, as a result of unequal crossing over or unequal sister-chromatid exchange, respectively. Our review indicates that mosaicism for tandem duplications is likely under-ascertained and that parental karyotyping of probands with non-mosaic tandem duplications should be performed.

Adult↗
PubMed2001

Mapping and genome sequence analysis of chromosome 5 regions involved in bladder cancer progression.

We studied the evolution of allelic losses on chromosome 5 by whole-organ histologic and genetic mapping in 234 mucosal DNA samples of 5 cystectomy specimens with invasive bladder cancer and preneoplastic changes in adjacent urothelium. The frequency of alterations in individual loci was verified on 32 tumors and 29 voided urine samples from patients with bladder cancer. Finally, deleted regions on chromosome 5 were integrated with the human genome contigs and sequence-based databases. Deleted regions on chromosome 5 involved in intraurothelial phases of bladder neoplasia defined by their nearest flanking markers and predicted size were identified as follows: q13.3-q22 (D5S424-D5S656; 38.8 centimorgan [cM]); q22-q31.1 (D5S656-D5S808; 19.2 cM), q31.1-q32 (D5S816-SPARC; 11.5 cM), and q34 (GABRA1-D5S415; 6.4 cM). The two most frequently deleted neighbor markers (D5S2055 and D5S818) mapping to q22-q31.1 defined a 9 cM region, which may contain genes that play an important role in early phases of urinary bladder carcinogenesis. Human genome database analysis provided an accurate map of deleted regions with positions of 138 known genes and revealed several smaller gene-rich areas representing putative targets for further mapping. The strategic approach presented here, which combines whole-organ histologic and genetic mapping with analysis of the rapidly emerging human genome sequence database, facilitates identification of genes potentially involved in early phases of bladder carcinogenesis.

Aged↗
PubMed2001

Bone marrow transplantation for T-B- severe combined immunodeficiency disease in Athabascan-speaking native Americans.

A distinct form of autosomal recessive T-B- severe combined immunodeficiency disease occurs with a high frequency among Athabascan-speaking Native Americans (SCIDA), including Navajo and Apache Indians from the southwestern US and Dene Indians from the Canadian Northwest Territories. The SCIDA gene has been linked to markers on chromosome 10p although its identity and role in the pathogenesis of this disease are unknown. We report our experience in treating 18 Navajo and Dene children with SCIDA between 1984 and 1999; 16 underwent bone marrow transplants (BMT). All children were symptomatic within 2 months of birth, had the T-B- NK(+)SCID phenotype and 67% presented with oral and/or genital ulcers. Three children had evidence of maternal engraftment prior to transplant. Two children died shortly after diagnosis. Three children required more than one BMT and 12 are alive with T cell reconstitution at a median follow-up of 7 years. Three children developed normal B cell immunity, two of whom received ablative conditioning therapy with either radiation or busulfan. Three of the four children who died received therapy with either radiation or busulfan and two of eight long-term survivors who were also recipients of cytotoxic chemotherapy have failed to develop secondary teeth. These results demonstrate the efficacy of BMT in treating infants with this distinct form of SCID, although B cell reconstitution remains a problem even with HLA-matched donors. Without conditioning, T cell engraftment is likely when closely HLA-matched donors are used. With T cell depletion of haplocompatible marrow, conditioning with immunosuppressive therapy may be necessary; however, children with SCIDA who were treated with intensive immunosuppressive and myeloablative therapy had a poor outcome.

B-Lymphocytes↗
PubMed2001

Efficient transduction of murine B lymphocytes and B lymphoma lines by modified adenoviral vectors: enhancement via targeting to FcR and heparan-containing proteins.

Murine lymphocytes are relatively refractory to efficient transfection or retroviral gene transduction. Adenovirus has been used as a vector to transduce a wide variety of cell types. Several advantages of adenoviruses are their ability to transduce non-cycling cells and to transduce the majority of cells in a population. Unfortunately, lymphocytes are not susceptible to infection with conventional adenovirus. Therefore, to express genes efficiently in murine B cells, we tested the ability of genetically modified adenovirus to transduce the beta-galactosidase gene. We found that adenovirus containing polylysine in the fiber knob was able to efficiently transduce lipopolysaccharide (LPS)-activated splenic B cells and the B lymphoma line M12.4.1; greater than 80% of the cells expressed beta-galactosidase activity. However, small resting B cells did not express activity unless treated with LPS after infection. This transduction was mediated by interaction with charged molecules since heparan-sulfate, and to a lesser degree chondroitan sulfate, inhibited the transduction. In addition, adenovirus containing a FLAG epitope in the fiber protein was used to target the FcR expressed on B cells using an anti-FLAG antibody. In the presence of anti-FLAG, the modified adenovirus was able to efficiently transduce LPS-activated B cells and several B cell lymphoma lines. Interestingly, in the absence of anti-FLAG, there was low level transduction in the LPS-blasts and in M12.4.1 that was not inhibited by soluble adenovirus fiber protein or agents that block RGD-integrin interactions. These results demonstrate that modified adenovirus efficiently transduce B lymphocytes which will be critical for targeting genes to normal or malignant B cells.

Adenoviridae↗
PubMed2001

Actions of the soy phytoestrogen genistein in models of human chronic disease: potential involvement of transforming growth factor beta.

The structural similarity, but non-identity, between 17beta-oestradiol and the soy phytoestrogen genistein suggests that the two compounds will have actions that may be identical in some target biological systems, but different in others. Epidermal growth factor (EGF)-stimulated proliferation of human mammary epithelial cells (that do not express the oestrogen receptor) was significantly suppressed at genistein concentrations (5-10 microM) that are attainable physiologically. Others have shown previously that transforming growth factor beta (TGFbeta) has similar growth-inhibitory effects on human cells. Analysis of the conditioned medium of human mammary epithelial cells exposed to genistein plus EGF showed increased levels of TGFbeta relative to those in the medium of cells exposed to EGF or genistein alone. Related experiments in a primate model of menopause demonstrated that ingestion of soy containing isoflavones was correlated with the suppression of neurodegeneration-relevant phosphorylation of the microtubule-associated protein tau, while intake of Premarin (a hormone replacement therapy that is commonly prescribed for women) was not correlated. The results discussed here indicate that genistein, and probably other related phytoestrogens, have pleiotropic actions, some of which may involve TGFbeta activity.

Animals↗
PubMed2001

A novel gene mutation that confers abnormal patterns of beta-carotene accumulation in cauliflower (Brassica oleracea var. botrytis).

The Or gene of cauliflower (Brassica oleracea var. botrytis) causes many tissues of the plant to accumulate carotenoids and turn orange, which is suggestive of a perturbation of the normal regulation of carotenogenesis. A series of experiments to explore the cellular basis of the carotenoid accumulation induced by the Or gene was completed. The Or gene causes obvious carotenoid accumulation in weakly or unpigmented tissues such as the curd, pith, leaf bases and shoot meristems, and cryptically in some cells of other organs, including the roots and developing fruits. The dominant carotenoid accumulated is beta-carotene, which can reach levels that are several hundred-fold higher than those in comparable wild-type tissues. The beta-carotene accumulates in plastids mainly as a component of massive, highly ordered sheets. The Or gene does not affect carotenoid composition of leaves, nor does it alter color and chromoplast appearance in flower petals. Interestingly, mRNA from carotenogenic and other isoprenoid biosynthetic genes upstream of the carotenoid pathway was detected both in orange tissues of the mutant, and in comparable unpigmented wild-type tissues. Thus the unpigmented wild-type tissues are likely to be competent to synthesize carotenoids, but this process is suppressed by an unidentified mechanism. Our results suggest that the Or gene may induce carotenoid accumulation by initiating the synthesis of a carotenoid deposition sink in the form of the large carotenoid-sequestering sheets.

Blotting, Northern↗
PubMed2001

Mutant NG108-15 cells (NG-CR72) deficient in GM1 synthase respond aberrantly to axonogenic stimuli and are vulnerable to calcium-induced apoptosis: they are rescued with LIGA-20.

The neuroblastoma x glioma NG108-15 hybrid cell line, a widely used model for the study of neuronal differentiation, contains a variety of gangliosides including GM1 and its sialosylated derivative, GD1a. To investigate the role of these a-series gangliotetraose gangliosides in neuritogenesis, we have obtained a mutated subclone of NG108-15 that is deficient in that family of gangliosides. NG108-15 cells were grown in the presence of cholera toxin, which killed the large majority of cells, and from the cholera-resistant survivors we isolated a clone, NG-CR72, that lacks GM1 and GD1a in the plasma and nuclear membranes. GM2 concentration was significantly higher in the plasma membrane. Enzyme assay indicated deficiency of UDP-Gal:GM2 galactosyltransferase (GM1 synthase), which was confirmed by incorporation studies with [3H]sphingosine. These cells resembled wild-type NG108-15 in extending dendritic processes in response to dendritogenic agents (retinoic acid, dibutyryl cAMP) but responded aberrantly to axonogenic stimuli (KCl, ionomycin) by extending unstable neurites that showed the cytoskeletal staining characteristic of dendrites. Moreover, mutant cells treated with the Ca2+ elevating axonogenic agents underwent apoptosis over time, attributed to dysfunction of Ca2+ regulatory mechanisms normally mediated by GM1. Such agents caused dramatic and sustained elevation of intracellular Ca2+ in mutant cells, in contrast to modest and temporary elevation in wild-type cells. Exogenous GM1, inserted into the plasma membrane, had no discernable protective effect on NG-CR72 cells whereas LIGA-20, a membrane-permeant derivative of GM1 that entered both plasma and nuclear membranes, blocked apoptosis, permitted extension of stable neurites, and attenuated the abnormal elevation of intracellular Ca2+.

Apoptosis↗
PubMed2001

Prostaglandin release by spinal cord injury mediates production of hydroxyl radical, malondialdehyde and cell death: a site of the neuroprotective action of methylprednisolone.

The present study explores in vivo whether and how prostaglandin F(2alpha) (PGF(2alpha)), a membrane phospholipid hydrolysis product, causes neuronal death. The concentration of PGF(2alpha) measured by microdialysis sampling increased threefold immediately following impact injury to the rat spinal cord. Administration of PGF(2alpha) into the cord through a dialysis fiber caused significant cell loss, increased extracellular levels of hydroxyl radicals and malondialdehyde - an end product of membrane lipid peroxidation - to 3.3 and 2.3 times basal levels, respectively. This suggests that PGF(2alpha)-induced cell death is partly due to hydroxyl radical-triggered peroxidation. Generating hydroxyl radical by administering Fenton's reagents into the cord through the fibers significantly increased malondialdehyde production - the first direct in vivo evidence that hydroxyl radical triggers membrane lipid peroxidation. Methylprednisolone significantly reduced the release of PGF(2alpha) upon spinal cord injury and blocked PGF(2alpha)-induced hydroxyl radical and malondialdehyde production, but did not significantly reduce Fenton's reagent-induced malondialdehyde production, despite the production of more malondialdehyde by PGF(2alpha). This suggests that methylprednisolone may not directly scavenge hydroxyl radical, and that its 'antioxidant' effect is a consequence of blocking the pathways for producing toxic PGF(2alpha) and for PGF(2alpha)-induced hydroxyl radical formation, thereby reducing membrane lipid peroxidation.

Animals↗
PubMed2001

Cerebrin prohormone processing, distribution and action in Aplysia californica.

The isolation, characterization, and bioactivity in the feeding circuitry of a novel neuropeptide in the Aplysia californica central nervous system are reported. The 17-residue amidated peptide, NGGTADALYNLPDLEKIamide, has been termed cerebrin due to its primary location in the cerebral ganglion. Liquid chromatographic purification guided by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry allowed the isolation of the peptide with purity adequate for Edman sequencing. The cerebrin cDNA has been characterized and encodes an 86 amino acid prohormone that predicts cerebrin and one additional peptide. Mapping using in situ hybridization and immunocytochemistry showed that cerebrin containing neuronal somata are localized almost exclusively in the cerebral ganglion, mostly in the F- and C-clusters. Both immunostaining and mass spectrometry demonstrated the presence of cerebrin in the neurohemal region of the upper labial nerve. In addition, immunoreactive processes were detected in the neuropil of all of the ganglia, including the buccal ganglia, and in some interganglionic connectives, including the cerebral-buccal connective. This suggests that cerebrin may also function as a local signaling molecule. Cerebrin has a profound effect on the feeding motor pattern elicited by the command-like neuron CBI-2, dramatically shortening the duration of the radula protraction in a concentration-dependent manner, mimicking the motor-pattern alterations observed in food induced arousal states. These findings suggest that cerebrin may contribute to food-induced arousal in the animal. Cerebrin-like immunoreactivity is also present in Lymnaea stagnalis suggesting that cerebrin-like peptides may be widespread throughout gastropoda.

Amino Acid Sequence↗
PubMed2001

Ectopic distal location of the papilla of vater in congenital biliary dilatation: Implications for pathogenesis.

BACKGROUND/PURPOSE: This study investigates the relationship between the location of the papilla of Vater and the length of the common channel in patients with congenital biliary dilatation (CBD). METHODS: Cholangiograms from 121 CBD patients and 13 normal controls were the subjects for this study. A length index defined as the length of the common channel divided by the height of the second lumbar vertebra was used for standardization. RESULTS: In the controls, the papilla of Vater was located in the middle of the descending or second part of the duodenum in all cases. In 39 (32.2%) of the 121 CBD patients papilla of Vater was located in the descending duodenum (group I), and in 82 (67.8%) it was distal to the descending duodenum (group II). The average length index of the common channel in group II was significantly longer than in group I (1.123 +/- 0.374 v 0.660 +/- 0.246; P <.001). Findings for the common bile duct were similar. CONCLUSIONS: There is a significantly higher incidence of ectopic distal location of the papilla of Vater in CBD patients than in controls. The more distal the location of the papilla of Vater, the longer the common bile duct and the common channel.

Adolescent↗
PubMed2001

Neuroprotective effects in gerbils of spiramine T from Spiraea japonica var. acuta.

The neuroprotective effects of spiramine T, an atisine-type diterpenoid alkaloid isolated from the Chinese herbal medicine Spiraea japonica var. acuta (Rosaceaee), on cerebral ischemia-reperfusion injury produced by 10-min bilateral occlusion of the common carotid arteries followed by 5-day reperfusion in gerbils were investigated. Intravenous spiramine T (0.38, 0.75, and 1.5 mg.kg-1) markedly reduced the stroke index, enhanced the recovery of EEG amplitude during reperfusion and decreased the concentrations of cortex calcium and LPO in a dose-dependent manner. However, no significant effects on water and sodium contents were observed. These results suggested that spiramine T exhibited protective effects on cerebral ischemia-reperfusion injury in gerbils, and its mechanism might be related to reducing calcium accumulation and lipid peroxidation. This is the first report on spiramine T as a natural product with neuroprotective effects.

Animals↗