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Biomedical subjects

L Ji

Publications and source records attributed to L Ji.

At least 55 records · Page 3Linked to original sources
PubMed1999

Induction of apoptosis and inhibition of tumorigenicity and tumor growth by adenovirus vector-mediated fragile histidine triad (FHIT) gene overexpression.

We studied the effects of fragile histidine triad (FHIT) gene overexpression mediated by an adenoviral vector, Ad-FHIT, on cell proliferation, apoptosis, and cell cycle kinetics in human cancer cells and on tumorigenicity and tumor growth in nude mice. Overexpression of the FHIT gene significantly inhibited cell growth in various Ad-FHIT-transduced human lung cancer cells and head and neck carcinoma cells with FHIT gene abnormalities, but not in normal human bronchial epithelial cells. Fewer than 20% of cells in all Ad-FHIT-transduced cells survived at 7 days after transduction. Overexpression of the FHIT gene induced cell apoptosis and altered cell cycle processes. The apoptotic cell population markedly increased, and cells accumulated in S phase after Ad-FHIT transduction. The tumorigenicity of human H1299 lung cancer cells transduced by Ad-FHIT, in comparison with that of the control transductants and untreated cells, was eliminated in vivo. Subcutaneous tumor growth in nude mice who received intratumoral injections of Ad-FHIT, at a total dose of 3 x 10(10) plaque-forming units/tumor for H1299 tumors and 4 x 10(10)/tumor for A549 tumors, were suppressed by more than 85% and 90%, respectively, compared with that in nude mice who received injections of empty vector at the same dose or with PBS alone. Together, our results suggest that the FHIT gene, when delivered at high efficiency by a recombinant adenoviral vector, functions as a tumor suppressor gene both in vitro and in vivo.

Acid Anhydride Hydrolases↗
PubMed1999

Reduced toxicity, attenuated immunogenicity and efficient mediation of human p53 gene expression in vivo by an adenovirus vector with deleted E1-E3 and inactivated E4 by GAL4-TATA promoter replacement.

A recombinant adenovirus with deleted E1 and E3, and E4-inactivated by replacing the E4 promoter with a synthetic promoter composed of a minimal TATA box and five consensus yeast GAL4-binding site elements was developed and used to express the human tumor suppresser gene p53. The toxicity and immunogenicity of this vector and vector-mediated p53 gene expression in vivo were studied in immunocompetent C3H and C57BL/6 mice. Expression of the late viral gene product, hexon protein, was observed in C3H and C57BL/6 mice injected with E4 wild-type adenovirus constructs Adv-cmv-beta-Gal (BG), Adv-cmv-hp53 (WT), and empty E1- vector Adv-E4 (EW) 3 to 28 days after injection, but was undetectable in mice treated with E4 modified empty E1- vector Adv-GAL4 (EG) or Adv-cmv-hp53-GAL4 (G4). Expression of the p53 gene was observed in both WT- and G4-injected C3H and C57BL/6 mouse livers from days 3 to 28. Ten weeks after injection, p53 gene expression was still detected in G4-treated C57BL/6 mice at similar levels, but was not detectable in WT-treated mice. Vector-induced liver toxicity was evaluated by analyzing serum transaminases (SGOT and SGPT) activities. In all cases, SGOT and SGPT activities were markedly decreased in EG-treated C3H and C57BL/6 mice compared with those in EW-treated mice on days 3, 7 and 14 after injection. In C57BL/6 mice, the total anti-adenoviral CTL activities were two- to three-fold higher in animals treated with EW vector than in those treated with EG vector. These results suggest that inactivation of the E4 promoter efficiently diminished the viral replication and the late viral gene expression, reduced host immune response and consequently reduced toxicity and prolonged the duration of transgene expression in vivo.

Adenoviridae↗
PubMed1999

Free radical activity, antioxidant enzyme, and glutathione changes with muscle stretch injury in rabbits.

The present study investigated changes in rate of free radical production, antioxidant enzyme activity, and glutathione status immediately after and 24 h after acute muscle stretch injury in 18 male New Zealand White rabbits. There was no change in free radical production in injured muscles, compared with noninjured controls, immediately after injury (time 0; P = 0.782). However, at 24 h postinjury, there was a 25% increase in free radical production in the injured muscles. Overall, there was an interaction (time and treatment) effect (P = 0.005) for free radical production. Antioxidant enzyme activity demonstrated a treatment (injured vs. control) and interaction effect for both glutathione peroxidase (P = 0.015) and glutathione reductase (P = 0.041). There was no evidence of lipid peroxidation damage, as measured by muscle malondialdehyde content. An interaction effect occurred for both reduced glutathione (P = 0.008) and total glutathione (P = 0.015). Morphological analysis (hematoxylin and eosin staining) showed significant polymorphonuclear cell infiltration of the damaged region at 24 h postinjury. We conclude that acute mechanical muscle stretch injury results in increased free radical production within 24 h after injury. Antioxidant enzyme and glutathione systems also appear to be affected during this early postinjury period.

Animals↗
PubMed1999

[Association of glucokinase gene with gestational diabetes mellitus in Chinese].

OBJECTIVE: To evaluate the role of glucokinase(GCK) gene in the pathogenesis of gestational diabetes mellitus (GDM) in Chinese. METHODS: Two microsatellite polymorphisms, GCK1 and GCK2 which located at approximately 10 Kb 3' and 6 Kb 5', respectively, of the human glucokinase gene on chromosome 7p13, were genotyped in 40 unrelated gestational diabetics and 43 controls. RESULTS: Four alleles (A, B, C, D) and seven genotypes were identified at the GCK1 locus. There was no significant difference in allele and genotype frequency between GDM and control groups at the GCK1 locus. For GCK2, four alleles(1,2,3,4) and eight genotypes were detected. When compared with control subjects, the GDM group had a much less frequency of the allele 2 (51.3% vs 69.8%, chi 2 = 5.965, P = 0.015), and a much more frequency of allele 3(31.3% vs 17.4%, chi 2 = 4.321, P = 0.038). Nine haplotypes of GCK1 and GCK2 were observed and haplotype B/2 was much less in GDM group(1.9% vs 19.4%, RR = 0.078 6, P = 0.003). Among the GDM patients, comparing with carriers of other alleles, the carriers of allele 3 of GCK2 locus had significantly elevated fasting and 2 hour's blood glucose levels during OGTT, and their insulin levels at 2nd and 3rd hour during the OGTT test were significantly decreased. Our results suggest that GCK gene was associated with Chinese GDM, and haplotype of GCK1/GCK2 B/2 was a protective factor for GDM.

Adult↗
PubMed1999

[GC-MS analysis of volatile constituents of rhizoma Heterosmilacis].

OBJECTIVE: To extract and analyze the volatile constituents from the dried rhizomes of Heterosmilax yunnanensis(A) and H. chinensis(B). METHODS: Qualitative and quantitative analysis were made by GC-MS and GC. RESULTS: Forty and forty-seven constituents were identified from A and B respectively, the identification rates being 74.85% and 81.26% respectively. CONCLUSION: The volatile constituents of A and B are almost the same, but slightly different in content.

Gas Chromatography-Mass Spectrometry↗
PubMed1999

[GC-MS analysis of essential oils from the roots of Saposhnikovia divaricata (Turcz.) Schischk, Libanotis laticalycina Shan et Sheh, Seseli yunnanense Franch. and Peucedanum dielsianum Fedde ex Wolff].

OBJECTIVE: To analyze the constituents of the essential oils from the roots of Saposhnikovia divaricata, Libanotis laticalycina, Seseli yunnanense and Peucedanum dielsianum. METHOD: GC-MS method was used. RESULT: 58 compounds were identified. CONCLUSION: To compare the constituents and their contents of 6 samples, 3 samples of S. divaricata growing in 3 places are similar, L. laticalycina, S. yunnanense and P. dielsianum are different from S. divaricata in varying degrees.

Alkynes↗
PubMed1999

[The visible spectra study of the conformation equilibrium of iron-metal-free porphyrin dimers].

A series of iron(III)-metal-porphyrin dimers linked with flexible alkoxyl chain at para position of two phenyl rings have been synthesized and characterized. An equilibrium of two conformations of porphyrin dimers (open and closed) has been studied by visible spectra. The intensity of absorption band 680 nm relates to equilibrium of two conformations. With the increase of the length of the alkoxyl chain,the closed conformation forms more easily. With the addition of axial ligand, the ferric ion of the dimers tends to bind with imidazole, and the intensity of the band 680 nm gradually decreases and disappears.

Dimerization↗
PubMed1999

[Studies on tailed metalloporphyrin coordination compounds. IX. Synthesis of tailed porphyrin with covalently linked phenylalanine and its fluorescence property].

A new tailed porphyrin with covalently linked phenylalanine 2 and its zinc complex 3 were synthesized. Intramolecular energy transfer (from singlet excited phenylalanine to porphyrin) was observed in compound 2 and 3. The influence of coordination chemistry factor on the fluorescence of porphyrin was also discussed.

Energy Transfer↗
PubMed1999

[The hydrogen bond between 5-(2-carboxyphenyl)-10, 15, 20-triphenylporphyrin and amino acid ester--study with UV-Vis titration and 1H-NMR].

The hydrogen bonds between the hydrogen of pyrrols in 5-(2-carboxyphenyl)-10,15,20-triphenylporphyrin and the oxygen of the carboxyl group of amino acid ester were confirmed by UV-Vis spectroscopic titration method and 1H-NMR. When amino acid ester was added to o-TPPCO2H solution in CHCl3, the Soret and Q and red-shifted dramatically and several isobestic points could be observed in UV-Vis spectra. In 1H-NMR, the signal of the hydrogen atoms of pyrrole in o-TPPCO2H (-2.78 ppm) decreased and a new signal in 0.260 ppm emerged, when o-TPPCO2H mixed with L-PheOEt at 1 : 1 (mol/mol).

Amino Acids↗
PubMed1998

Effects of endoglycoceramidase or D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol on glucose uptake, glycolysis, and mitochondrial respiration in HL60 cells.

The glycosphingolipid content of HL60 cells was reduced by endoglycoceramidase, an enzyme which specifically hydrolyzes glycosphingolipids on the cell surface, or by D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor which specifically reduces the activity of UDP-glucose:ceramide glucosyltransferase. Reduction of the glycosphingolipid content by both reagents resulted in enhancement of glucose uptake and glycolysis. Neither of these effects was observed in the presence of cytochalasin B, an inhibitor of facilitated glucose transport. The uptake of radiolabeled 3-O-methylglucose by the cells was not affected by treatment with either of the reagents, indicating no activation of the glucose transporter. On the other hand, both reagents decreased the level of ATP and CO2 production. The molecule mediating these effects appeared to be ceramide, since both treatments actually increased the intracellular ceramide content, and the cell-permeable short-chain ceramide N-acetylsphingosine, but not sphingosine, sphinganine, or palmitic acid, mimicked the effects of both reagents to comparable extents. Finally, the function of electron transport in isolated mitochondria fractions was found to be reduced by treatment of the cells with N-acetylsphingosine. These results strongly suggest that ceramide may affect mitochondrial respiration.

Cell Membrane Permeability↗
PubMed1998

A synthetic human Agouti-related protein-(83-132)-NH2 fragment is a potent inhibitor of melanocortin receptor function.

Chemical synthesis of Agouti proteins - Agouti and Agouti-related proteins - is complicated by their large size and by multiple cysteine residues located in the carboxyl terminal regions. Three human Agouti-related protein (AGRP) fragments, two of which correspond to a proposed endoprotease cleavage site between amino acids 82 and 83, were synthesized and tested for anti-melanotropic activity using Xenopus laevis dermal melanophores. Amino-terminal fragments AGRP(25-51) and (54-82) were devoid of significant antagonist activity, whereas the amidated carboxyl-terminal AGRP fragment (83-132)-NH2 was potently active with an inhibitory equilibrium dissociation constant (Ki) of 0.7 nM. The ability to synthesize functionally active AGRP should help unravel its role in the central nervous system and its unusual properties with respect to interaction with the melanocortin family of G-protein coupled receptors.

Agouti Signaling Protein↗
PubMed1998

Evaluation of GAL4/TATA in vivo. Induction of transgene expression by adenovirally mediated gene codelivery.

A synthetic GAL4-responsive promoter consisting of five GAL4-binding sites and a TATA box (GAL4/TATA) was evaluated for its transcriptional activity in an adenoviral backbone using luciferase as the reporter. Basal luciferase activities in vitro were the same for cells infected with either adenovirus-containing luciferase cDNA driven by GAL4/TATA (Ad/GT-Luc) or adenovirus-containing luciferase cDNA not driven by a promoter (Ad/PO-Luc). In vitro induction of GAL4/TATA by coinfection of cells with adenovirus expressing the GAL4/VP16 fusion protein (Ad/3-phosphoglycerate kinase (PGK)-GV16) was dose-dependent and reached as high as 4 x 10(4)- to 9 x 10(4)-fold above basal levels when GAL4/TATA and GAL4/VP16 were delivered at a ratio of 10:1. In vivo studies in Balb/c mice showed no detectable luciferase activities in liver or other tissues examined in mice infused with either Ad/GT-Luc or Ad/PO-Luc. High levels of luciferase activity were, however, elicited when animals were infused with Ad/GT-Luc and Ad/PGK-GV16. Together, these results suggest that combination of the GAL4 gene regulatory system with adenovirally mediated in vivo gene delivery may be applicable to the in vivo evaluation of promoter activities and in vivo targeting of gene expression.

Adenoviridae↗
PubMed1998

Suppression of the immune response to an adenovirus vector and enhancement of intratumoral transgene expression by low-dose etoposide.

Adenoviral vectors are commonly used in gene therapy trials because of their efficiency in gene transfer. However, their use is limited by cellular and humoral immune responses that result in temporary transgene expression and reduced efficacy of repeated vector administration. We hypothesized that certain oncolytic agents commonly used to treat cancer patients could suppress the immune response to adenoviral vectors, and enable repeated adenovirus-mediated cancer gene therapy. Etoposide and cyclophosphamide were tested for their ability to suppress the humoral and cellular immune responses to an adenoviral vector in immunocompetent C3H mice. Intratumoral transgene expression was monitored in adenovirus-immunized animals treated with etoposide or cyclophosphamide. Neutralizing antibodies to adenovirus and cytotoxic T lymphocyte (CTL) lysis of virally transduced cells were significantly suppressed in mice treated with etoposide at 2 or 10 mg/kg/day or cyclophosphamide at 10 mg/kg/day compared with untreated mice (P < 0.05). Significantly larger areas of gene transduction were observed in treated animals compared with untreated mice or the mice treated with cyclophosphamide at 2 mg/kg/day (P < 0.05). Our results suggest that repeated adenovirally mediated gene therapy is achievable in cancer patients who are concurrently undergoing treatment with chemotherapy.

Adenoviridae↗
PubMed1998

Prednisone and low-dose activated prothrombin complex concentrates for FVIII inhibitor in nonhaemophilic patients.

Eight nonhaemophilic patients with factor VIII (FVIII) inhibitors were reported. There was no difference in sex distribution. Median age at diagnosis was 62 years (ranging from 14 to 73 years). No associated disorders were revealed and all the patients were presented with severe muscular or arthral bleeding. Inhibitor titre was measured by the Bethesda method, which were 6.4, 126.0, 155.0, 4.8, 56.0, 13.5, 35.0 and 150.0 BU mL-1, respectively, at diagnosis. FVIII:C levels were less than 1 U dL-1 in seven patients and less than 2 U dL-1 in one patient. The median vWF:Ag level was 210% (ranging from 80% to 340%). All the patients had good response to activated prothrombin complex concentrates for acute bleeding episodes and prednisone for inhibitor elimination. Inhibitors completely eliminated in seven patients within a follow-up duration over 1 year, and one patient died of intracranial haemorrhage when her inhibitor titre decreased to 4.5 BU mL-1 and FVIII:C increased to 21 U dL-1.

Adolescent↗
PubMed1998

Gender-specific association of M235T polymorphism in angiotensinogen gene and diabetic nephropathy in NIDDM.

This study examined the association between the development of nephropathy in non-insulin-dependent diabetes mellitus (NIDDM) patients and M235T polymorphism in the angiotensinogen gene. White NIDDM patients with diabetic nephropathy (case subjects, n = 117) and patients without any evidence of nephropathy and > or = 10 years of NIDDM (control subjects, n = 125) were selected from among patients of the Joslin Diabetes Center and examined. In addition to a standardized examination, blood was drawn for DNA and determination of M235T genotypes at the angiotensinogen locus. For the angiotensinogen gene, the frequency of the genotype 235T/235T, known to be associated with essential hypertension, was higher among case subjects with nephropathy than in control subjects without this complication. This difference, expressed as the odds ratio for nephropathy among 235T/235T homozygotes in comparison with all other genotypes, was 2.2 (95% confidence interval, 1.1 to 4.4). The difference, however, was confined to men (odds ratio, 4.8; 95% confidence interval, 1.5 to 14.9), with the distribution of genotypes in case and control subjects being equal among women (odds ratio, 1.1). DNA polymorphism M235T in the angiotensinogen gene, which is associated with higher expression of this gene, contributes to the risk of diabetic nephropathy in NIDDM men but not in women.

Adult↗