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Biomedical subjects

L Ge

Publications and source records attributed to L Ge.

At least 37 records · Page 2Linked to original sources

Characterization of a new genotype of measles virus detected in China and England.

We report the co-circulation of a new lineage of measles virus (MV) and an Edmonston-like (Ed-like) genotype of MV in China during 1995-7. Sequence analysis of 25 strains was performed on a 282 nucleotides (nt) region of the nucleoprotein (N) gene, a 450-nt region of the haemagglutinin (H) gene and a 152-nt region of the matrix (M) gene by direct sequencing of RT-PCR amplicons obtained from clinical specimens. The entire H gene was sequenced from two strains. The results showed that 24/25 Chinese strains belonged to a new genogroup and were distinct from the vaccine strains used in China and the UK, and also from MV strains previously described in Europe, Africa and the USA. The remaining strain was Ed-like. Two strains of the new genotype (IV) and one of the Ed-like genotype were also detected in the UK in 1996.

Adolescent↗

Determination of absorption characteristics of AG337, a novel thymidylate synthase inhibitor, using a perfused rat intestinal model.

The purpose of this study was to determine the intestinal absorption characteristics of AG337, a mechanism-based inhibitor of thymidylate synthase, using a perfused rat intestinal model. Effects of site, pH, temperature, concentration, Na+, and inhibitors on the absorption of AG337 were determined, after the compound was shown to be stable in buffers of various pH, blank perfusate, and intestinal homogenate. The results indicated that absorption of AG337 was temperature-, pH-, Na+-, concentration-, and site-dependent. The best site of absorption is duodenum, where the absorption was 3-10 times (p < 0. 05) higher than absorption at jejunum, ileum, and colon. Among the four pH's studied, the best was at pH 6.5 (p < 0.05). Absorption was 80% lower in the absence of Na+, and 75% lower when the temperature of the perfusate was decreased to 4 degreesC. Permeability of AG337 also decreased about 75% when the concentration was raised to 100 microM. These results suggest that a nutrient carrier may be involved in the transport of AG337. To determine the carrier responsible for the absorption of AG337, its absorption was determined in the presence of various inhibitors at different concentrations. The results indicated that transport of AG337 was inhibited significantly (p < 0.01) by 100 microM of adenine, hypoxanthine, and xanthine. The transport was also inhibited significantly (p < 0.01) by a mixture of 100 microM each of adenine, hypoxanthine, and xanthine, but not by a mixture of 100 microM each of thymine and uracil. A higher concentration of hypoxanthine resulted in increased inhibition. In contrast, prototypical inhibitors of nucleoside transporter, dipyridamole and nitrobenzylthioinosine (NBMPR), did not significantly decrease the transport of AG337. The results also showed that absorption of AG337 had a significant nonsaturable component, with a nonsaturable Pw of 0.8. In conclusion, absorption of AG337 in the rat intestine has been shown to be mainly via a purine base carrier with a significant nonsaturable component.

Animals↗

Expression of the Cell Adhesion Molecule CD44 in Human Lung Tumors and Cell Lines.

Background: The purpose of this study was to examine the expression of the cell adhesion molecule CD44 in normal lung, primary and metastatic lung tumors, and cell lines derived from primary lung carcinomas. Methods and Results: A total of 68 lung specimens including normal tissue and primary and metastatic tumors, as well as 28 cell lines cultured from primary lung tumors with high recurrence, were examined for CD44 expression by semiquantitative reverse transcription polymerase chain reaction. Variant exon expression was confirmed by Southern blotting and hybridization of particular samples. In tumor tissues, loss of CD44 variant expression correlated with increasing tumor stage; a smaller percentage of more aggressive and poorly differentiated tumors expressed CD44v. Tumors metastatic to the lung were negative for CD44 variant expression. In primary lung cell lines, as in tumor tissue, tumors of higher histologic grade were characterized by loss of CD44 variant expression. Conclusion: CD44 isoform expression in normal lung and tumor tissues and cell lines revealed an overall decrease in CD44 alternative splicing in lung neoplasms of increased malignancy.

Journal Article↗

[Effects of carbon disulfide on neurotransmitter and its metabolites in rats].

OBJECTIVE: In order to study the mechanism of neurotoxic effects of carbon disulfide (CS2) on animal behavior. METHODS: Changes in monoamine transmitter, amino acid transmitter and their metabolites in brain tissues were observed in rats exposed to CS2 at levels of 0, 1,200 and 2,400 mg/m3 respectively, for two months, with high performance liquid chromatography. RESULTS: Indicated that exposure to CS2 could cause decrease in 3-methoxy-4-hydroxy mandelic acid (VMA), increase in 3,4-dioxybenzoic acid, a metabolite of dopamine, and high vanillic acid in rat straitum, decrease in excitatory amino acids and their metabolites (glutamine, aspartic acid and asparagine), with a certain relationship between contents of VMA, aspartic acid and asparagine and changes in neurobehavior. CONCLUSION: Disturbance of neurotransmitter metabolism plays an important role in neurotoxic effects of CS2.

Animals↗

[Geneotic analysis of wild type measles viruses circulating in China during 1995-1997].

To investigate the molecular epidemiology of measles virus (MV) in China, sequence analysis of MV was performed based on a 282-nt region of the nucleoprotein (N) gene and a 450-nt region of heamaglutinin (H) gene by direct sequencing of RT-PCR amplicons obtained from clinical specimens. Results revealed that one MV strain belonged to ED-like genotype and remainder strains were clustered into a new genotype which was distinct from Chinese vaccine strains and MV strains circulating in other countries, as previously described representing a new genotype. There was up to 15.4% divergence in the nt-282 N gene and 10.8% divergence in the nt-450 H gene between the new genotype and other genotypes.

China↗

Selectively-infective phage (SIP): a mechanistic dissection of a novel in vivo selection for protein-ligand interactions.

Selectively-infective phage (SIP) is a novel methodology for the in vivo selection of interacting protein-ligand pairs. It consists of two components, (1) a phage particle made non-infective by replacing its N-terminal domains of geneIII protein (gIIIp) with a ligand-binding protein, and (2) an "adapter" molecule in which the ligand is linked to those N-terminal domains of gIIIp which are missing from the phage particle. Infectivity is restored when the displayed protein binds to the ligand and thereby attaches the missing N-terminal domains of gIIIp to the phage particle. Phage propagation is thus strictly dependent on the protein-ligand interaction. We have shown that the insertion of beta-lactamase into different positions of gIIIp, mimicking the insertion of a protein-ligand pair, led to highly infective phage particles. Any phages lacking the first N-terminal domain were not infective at all. In contrast, those lacking only the second N-terminal domain showed low infectivity irrespective of the presence or absence of the F-pilus on the recipient cell, which could be enhanced by addition of calcium. An anti-fluorescein scFv antibody and its antigen fluorescein were examined as a protein-ligand model system for SIP experiments. Adapter molecules, synthesized by chemical coupling of fluorescein to the purified N-terminal domains, were mixed with non-infective anti-fluorescein scFv-displaying phages. Infection events were strictly dependent on fluorescein being coupled to the N-terminal domains and showed a strong dependence on the adapter concentration. Up to 10(6) antigen-specific events could be obtained from 10(10) input phages, compared to only one antigen-independent event. Since no separation of binders and non-binders is necessary, SIP is promising as a rapid procedure to select for high affinity interactions.

Calcium Chloride↗

Risk factors for human cysticercosis morbidity: a population-based case-control study.

A population-based case-control study to determine social and behavioural risk factors for Taenia solium cysticercosis in humans was carried out in a rural area. Shandong province, China. Forty-eight cases with cysticercosis were ascertained through a prevalence survey conducted among 7281 persons in 1993. For each case, four controls residing in the same village and matched for age and sex were randomly selected. Information regarding demographic, social and behavioural factors was collected during house visits through interviews and direct observation. Risk factors strongly associated with human cysticercosis included poor personal hygiene, being unable to recognize cysticerci-containing meat, poor pig-raising practices and a history of passing tapeworm proglottides. The results indicate that health education in combination with chemotherapy for taeniasis is required for the control of cysticercosis in humans.

Adolescent↗

[Comparison of defibrase and heparin in the prevention of thrombosis after coronary intervention].

To evaluate the effects of defibrase on thrombosis after coronary intervention. 12 dogs were randomized into group to be treated with defibrase (n = 6) and another group with heparin (n = 6) after coronary intervention. After implanting stents in coronary arteries, canine platelets labeled with 99mTc-hexamethyl propylene amine oxime were re-transfused into blood circulation. The stenting vessels were imaged with gamma-camera in vivo and in vitro at the 4th and 24th hour, then the relative radioactivity of stenting vessels was quantified. The isolated stenting vessels were weighted and measured with gamma-counter and the number of deposited platelets was calculated. The relative radioactivity and the number of deposited platelets were lower in the group of defibrase than in the group of heparin (P < 0.01). Compared with heparin, defibrase has more potent effect on the prevention of thrombus formation and may reduce the early-reocclusion after coronary intervention.

Angioplasty, Balloon, Coronary↗

[Effect of intestinal lymph on blood pressure of rat].

The effect of intestinal lymph on blood pressure in rats was observed by the methods of lymph drainage and lymph infusion. The results obtained are as follows: (1) After 150 min of the lymph drained through the cannula of intestinal lymph duct, the blood pressure was significantly lower than that of the sham group (P < 0.05). (2) Equivalent albumin or intralipid infusion was not able to prevent the decrease in blood pressure when the lymph was lost. But in jugular-intestinal lymph duct shunt group, no significant blood pressure decrease could be seen during the drainage procedure for 4 h. (3) The blood pressure of rat with serious hemorrhagic shock could be increased significantly with a little amount of intestinal lymph infusion, and the rats survived longer than those of the control group (P < 0.05-0.01). The above results suggest that the intestinal lymph may play an important role in maintenance of blood pressure, in addition to the known function of lymphatic system by returning tissue fluid to blood and maintaining circulating blood volume.

Animals↗

Prime factors.

We use Voiculescu's free probability theory to prove the existence of prime factors, hence answering a longstanding problem in the theory of von Neumann algebras.

Journal Article↗

Localization of the gene responsible for the op (osteopetrotic) defect in rats on chromosome 10.

Osteopetrosis, a skeletal disorder of inadequate bone resorption with an abnormal increase in skeletal mass, results from a variety of independent single gene mutations that affect osteoclast differentiation and/or function. The osteopetrotic defect, op, is one of four spontaneous, nonallelic mutations in rats that result in osteopetrosis. In intercross progeny of (BN/SsN x LEW/SsN. +/op) F1 carriers, we mapped this locus by linkage analysis with microsatellite markers to rat chromosome 10. The linkage group contained, as well as op, 15 anonymous DNA loci and 9 DNA loci associated with genes (interleukin-3, myosin heavy chain [skeletal, embryonic], asialoglycoprotein receptor [hepatic lectin]-1, vesicle-associated membrane protein [synaptobrevin-2], sex hormone binding globulin, aldolase C, nitric oxide synthase [inducible], erythroblastic leukemia avian viral oncogene homolog-2, and proline-rich protein). The markers for these loci include nine not previously reported. The op locus mapped to the end of the chromosome 10 linkage group, within 1 cM of the anonymous DNA locus, D10Mit6. Based on its location, the op gene is likely to be distinct from seven described mutations in mice as well as three other mutations in rats. These results may permit a positional cloning strategy to be undertaken to identify the gene and mutation underlying the op defect.

Animals↗

Sodium butyrate is a potent modulator of smooth muscle cell proliferation and gene expression.

Sodium butyrate is a small, naturally occurring molecule with demonstrated activity on cell growth and differentiation. However, its effect on smooth muscle cells had not been examined. We have found that sodium butyrate and its more stable in vivo analogue tributyrin are potent DNA synthesis and cell proliferation inhibitors. The inhibitory activity of sodium butyrate was not mediated by an elevation of endogenous cAMP levels, a known pathway involved in SMC growth-arrest and maintenance of the contractile phenotype. Consistent with the concept that its activity is mediated by a cAMP-independent pathway, butyrate was able to augment the maximum DNA synthesis inhibitory effect of various agents that elevated intracellular cAMP levels. Additionally, butyrate present for just the initial 8 h or present as late as 16 h after serum addition was able to inhibit DNA synthesis. By contrast, the cAMP analogue, 8Br-cAMP had to be present throughout the entire G0 to S phase of the cell cycle to effectively inhibit DNA synthesis. These results indicated that sodium butyrate inhibited SMC growth through a cAMP-independent mechanism. We also found that sodium butyrate was unable to abrogate the expression of the serum-inducible genes c-fos, c-myc, Ki-Ras and PS4, but was able to directly stimulate the expression of PS4 and thrombospondin. These results indicate that a number of important early G1 events initiated by serum growth factors are unaltered by sodium butyrate and that this compound is able to directly stimulate the expression of certain genes normally associated with SMC proliferation.

Adenosine Monophosphate↗

[Experimental study on in vivo hematopoietic regulation of IL-6 gene-transfected tumor vaccine].

In the present study, we investigated the effects on hematopoiesis of inactivated vaccines prepared from mouse erythroid leukemia cells (FBL-3) transfected with IL-6 gene. After treatment with IL-6 gene-transfected FBL-3 cells, the platelet count in mice started to increase at day 4, reached its maximum at day 10 and lasted for 25 days. The neutrophil count also increased significantly, but WBC count remained unchanged. The CFU-GM and CFU-MK were elevated to some extent in bone marrow and spleen. These results indicated that in addition to augmentation of antitumor immunity, IL-6 gene-transfected tumor vaccine could promote hematopoietic functions in bone marrow and spleen, and elevate platelet and neutrophil counts in peripheral blood. This approach to gene therapy may be applicable in leukemia treatment, especially for thrombocytopenia related to leukemia or chemotherapy.

Animals↗

Functional antibody single-chain fragments from the cytoplasm of Escherichia coli: influence of thioredoxin reductase (TrxB).

The cytoplasmic expression of a functional antibody (Ab) fragment, containing the correct intradomain disulfide bonds, was investigated in E. coli. We used a single-chain Fv (scFv) fragment of the levan-binding Ab ABPC48, which was shown to be functional only in the presence of the disulfide bonds. Significant amounts of functional, disulfide-containing scFv could be produced in the cytoplasm of E. coli in the absence of thioredoxin reductase (TrxB) activity. The amount of soluble protein remained largely unchanged by this null mutation. A stronger promoter did not result in further improved yields of functional Ab fragment, despite much higher protein production, suggesting that inefficient disulfide formation was still limiting the yield of active scFv. This method of expressing functional Ab fragments in the cytoplasm of E. coli may be important for screening and selection systems.

Antigen-Antibody Reactions↗

A mouse Ig kappa domain of very unusual framework structure loses function when converted to the consensus.

Antibody gene sequences, particularly those of kappa light chains, are very well conserved in the framework region, and the variability is concentrated in the complementarity-determining regions (CDR). We now found that the murine antibody 93-6 (Djavadi-Ohaniance, L., Friguet, B., and Goldberg, M. (1984) Biochemistry 23, 97-104) whose Fab fragment binds the beta-subunit of Escherichia coli tryptophan synthase with high affinity (Kd of 6.7.10(-9) M) has a highly unusual kappa light chain framework, which is crucial for the function of this antibody. It carries an insertion of 8 amino acids in a conserved framework loop that faces the antigen, and its framework region 2 (FR2) which precedes CDR2 is shortened by one amino acid, normally leucine and part of an absolutely conserved beta-bulge preceding CDR2. Removal of the insertion to restore the consensus sequence reduced the binding affinity of 93-6 by a factor 3, while insertion of the missing leucine into FR2 completely abolished binding.

Amino Acid Sequence↗

Isolation of a cDNA encoding a growth-arrest associated gene and characterization of its regulation.

We are interested in understanding the molecular events associated with the growth-arrest of vascular SMCs. We constructed a subtracted cDNA library enriched in nucleotide sequences associated with quiescent SMCs. This library was screened with similarly subtracted 32P-labeled cDNAs to identify growth-arrest associated cDNA clones. Characterization of 19 of these cDNA clones revealed that 9 hybridized to mRNAs that exhibited a 2-3-fold increase in growth-arrested SMCs. In addition, two other cDNAs hybridized to a 5 Kb mRNA that was elevated approximately 10-fold in high density growth-arrested SMCs. Genomic Southern blot hybridization and DNA sequencing analysis indicated that these cDNAs encoded the same gene (LG7) and that this gene may be a member of a multigene family or that it may contain a sequence shared by other unrelated genes. Augmented expression of LG7 was associated with both high cell density and serum deprivation induced growth-arrest. LG7 mRNA expression was down-regulated when SMCs were incubated with FBS or with reagents that arrest cells in early S-phase. Additional analysis with cell cycle specific inhibitors indicated that LG7 mRNA levels were also low when cells were blocked at the G2 phase of the cell cycle but blockage at mitosis resulted in an elevated level of LG7 mRNA. We further demonstrated that the expression of LG7 was dependent on the presence of a relatively labile protein since protein synthesis inhibitors specifically blocked the expression of this mRNA but not the mRNA expression of alpha 1(III) collagen or ferritin H-chain. Finally, we demonstrated that Bt2cAMP was able to induce mRNA expression of LG7 within 2 h, suggesting that this gene may be directly regulated via the cyclic-AMP-dependent protein kinase pathway.

Animals↗