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Biomedical subjects

G Luo

Publications and source records attributed to G Luo.

At least 91 records · Page 5Linked to original sources
PubMed1998

Cloning and expression of murine CYP2Cs and their ability to metabolize arachidonic acid.

Five murine cytochrome P450 (CYP) 2C cDNAs were cloned and characterized, including four new members of this subfamily: CYP2C37, CYP2C38, CYP2C39, and CYP2C40. The cDNAs ranged from 1716 to 1812 bp in length and encoded polypeptides of 490 amino acid residues except for CYP2C40, which contained an additional glutamic acid residue at the carboxyl terminus. The amino acid identity of the murine CYP2Cs ranged from 69 to 92%, while the overall amino acid identity was 60%; however, within the six putative substrate recognition sites the identity was only 25 to 41%, suggesting possible differences in substrate specificity and product profiles. The CYP2C cDNAs were expressed in Escherichia coli following modification of the N-terminus. All five recombinant CYP2Cs metabolized arachidonic acid, but with different metabolic profiles and catalytic rates. Based on coelution with authentic standards on reverse-phase HPLC, themajor metabolites were tentatively identified asfollows: CYP2C29 and CYP2C39 produced 14, 15-cis-epoxyeicosatrienoic acid (EET); CYP2C37 produced 12-hydroxyeicosatetraenoic acid (HETE); CYP2C38 produced 11,12-EET; and CYP2C40 produced an unidentified metabolite that coeluted with 16-,17-, and 18-HETEs. The turnover numbers for CYP2C29, CYP2C37, CYP2C38, CYP2C39, and CYP2C40 were 0.34, 1.12, 5.15, 0.51, and 0.15 nmol/nmol/min, respectively. Reverse transcriptase-polymerase chain reaction demonstrated the presence of CYP2C29 mRNA in liver as well as in extrahepatic tissues including brain, kidney, lung, heart, and intestine. CYP2C38 and CYP2C40 were found in liver, brain, kidney, and intestine, with trace amounts in lung and heart, while CYP2C37 and CYP2C39 appeared to be liver specific.

Amino Acid Sequence↗
PubMed1998

Chromosomal transposition of a Tc1/mariner-like element in mouse embryonic stem cells.

Mouse has become an increasingly important organism for modeling human diseases and for determining gene function in a mammalian context. Unfortunately, transposon-tagged mutagenesis, one of the most valuable tools for functional genomics, still is not available in this organism. On the other hand, it has long been speculated that members of the Tc1/mariner-like elements may be less dependent on host factors and, hence, can be introduced into heterologous organisms. However, this prediction has not been realized in mice. We report here the chromosomal transposition of the Sleeping Beauty (SB) element in mouse embryonic stem cells, providing evidence that it can be used as an in vivo mutagen in mice.

Animals↗
PubMed1998

Biochemical characterization of selenium-containing catalytic antibody as a cytosolic glutathione peroxidase mimic.

A selenium-containing catalytic antibody (Se-4A4), prepared by converting reactive serine residues of a monoclonal antibody (4A4) raised against a GSH derivative into selenocysteines, acts as a mimic of cytosolic glutathione peroxidase (cGPX). To clarify the mechanism of action of this catalytic antibody, detailed studies on kinetic behaviour and biological activity were carried out. A rate of acceleration (kcat/Km/kuncat) 10(7)-fold that of the uncatalytic reaction is observed. Under similar conditions, the turnover number (kcat) of Se-4A4 is 42% of that of the natural rabbit liver cGPX. The Se-4A4 reaction involves a Ping Pong mechanism, which is the same as that of the natural cGPX. The selenocysteine residue is located in the binding site of the antibody and is shown to be crucial for this activity. Of the thiol compounds tested, only GSH is able to serve as substrate for Se-4A4. It was demonstrated, using the free-radical-damage system (hypoxanthine/xanthine oxidase) of cardiac mitochondria, that Se-4A4 can protect mitochondria from free-radical damage at least 10(4)-fold more effectively than the natural cGPX.

Antibodies, Catalytic↗
PubMed1998

Discovery and evaluation of a series of 3-acylindole imidazopyridine platelet-activating factor antagonists.

Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N, N-dimethylcarbamoyl)-4-ethynyl-3-[3-fluoro-4-[(1H-2-methylimidazo[4,5-c] pyrid-1-yl)methyl]benzoyl]indole hydrochloride (ABT-491, 22 m.HCl) which has been evaluated extensively and is currently in clinical development.

Animals↗
PubMed1998

A General Formulation for Unidimensional Unfolding and Pairwise Preference Models: Making Explicit the Latitude of Acceptance.

Probabilistic unfolding models for direct responses of persons to statements are characterised by single peaked response functions. The range in which a positive response is most likely is termed the latitude of acceptance, a well known but little researched concept in the modelling of attitude measurement. This paper derives a general form for probabilistic unfolding models in which a natural parameter characterises the latitude of acceptance. It is shown that a number of already known models for unfolding can be reexpressed in this general form with different operational functions and that, in doing so, the implied latitude of acceptance for these models is identified. It is also shown that other unfolding models can be generated readily by specifying the operational function of the general form. A general form for pairwise preference models is also presented. A discussion on the latitude of acceptance parameter as a scale parameter is also provided. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Prolactin and growth hormone signal transduction in lymphohaemopoietic cells.

The peptide hormones, prolactin (PRL) and growth hormone (GH), are known to regulate numerous target tissues. Among such targets are cells of the immune system, including T cells, B cells, macrophages and natural killer cells. We have cloned a panel of PRL- and GH-inducible T cell genes for use in studies to understand how these hormones through the expression of these genes modulate the biology of immune function cells. This article focuses on the signalling pathways emanating from the PRL receptor (PRL-R) and GH receptor (GH-R), and the expression of PRL-inducible target genes.

Animals↗
PubMed1998

Lactogenic hormone signal transduction.

The peptide hormone prolactin (PRL) is known to regulate numerous target tissues. Among the less well-known targets are cells of the immune system, including T cells, B cells, and macrophages. Our laboratory has cloned a panel of PRL-inducible T-cell activation genes for use in studies investigating how PRL modulates the biology of cells of the immune system. This article focuses on two such PRL-inducible genes. One is a transcription factor called interferon regulatory factor-1, whose expression is regulated by signaling molecules along the PRL-inducible JAK/Stat signaling pathway. These signaling molecules include Stat1 and CBP as positive mediators and, unexpectedly, Stat5b as a negative mediator. A second PRL-inducible gene is c15/RNUDC, a novel nuclear movement protein, which may provide a link between PRL signaling and signaling via the lipid second messenger, platelet activating factor.

Animals↗
PubMed1998

Effects of vitamin C on myocardial mitochondrial function and ATP content in hypoxic rats.

AIM: To observe the effects of large dose of vitamin C (Vc) on myocardial mitochondrial function, ATP content, and myocardial structure in acute and chronic hypoxic rats. METHODS: Rats were exposed to a simulated altitude 4000 m (barometric pressure = 43 kPa) for 3 and 30 d. Vc (0.75 g.kg-1.d-1) was injected i.p. The heart mitochondrial respiratory function were determined by Clark-type O2 electrode; mitochondrial membrane fluidity (MMF) were assayed through fluorescence polarizative method; the contents of ATP, ADP, and AMP in myocardial tissue were measured with HPLC. RESULTS: After administration of Vc, the ATP content was increased from 35 +/- 3 mg.g-1 to 53 +/- 3 mg.g-1 in acute hypoxic rats (P < 0.01), from 42 +/- 4 mg.g-1 to 48 +/- 3 mg.g-1 in chronic hypoxic rats (P < 0.01); Pa, O2 was increased from 7.2 +/- 1.4 kPa to 9.5 +/- 1.2 kPa in acute hypoxic rats (P < 0.01); mitochondrial respiratory control rate (RCR) was increased from 2.1 +/- 0.6 to 4.7 +/- 0.5 in acute hypoxic rats (P < 0.01), and from 3.3 +/- 0.7 to 4.5 +/- 0.6 in chronic hypoxic rats (P < 0.01); MMF was increased in acute and chronic hypoxic rats (P < 0.05); the degree of myocardial necrosis in vitamin C preventive rats was attenuated as compared with those of acute hypoxic rats. CONCLUSION: Vc is effective on improving myocardial energy metabolism and protecting against myocardial structural injury in hypoxic rats.

Adenosine Triphosphate↗
PubMed1998

[The inhibitory effect of wild-type p53 gene on the growth and proliferation of lingual squamous cell carcinoma cell line Tca8113 in nude mice].

The aim of this study was to observe the growth and proliferation of the Tca8113 cell line in nude mice after the wild-type p53 gene has been transfered by electroporation. The experiment consisted of four groups: the wild-type p53 gene, blank control plasmid, the mutant p53 gene, and blank control into which no gene was transfered. After the gene was transfected, the cells were planted into 16 nude mice respectively. When the tumor formed, the nude mice were killed and the tumors were studied by regular pathology, stereology and immunohistochemistry. The results showed that in the wild-type p53 gene group, the tumors weighed less heavy, the pathological mitosis decreased markedly, and stereologically, the ratio of the area of necrosis to the total tumorous area was smaller. Similarly, the count of the proliferation cell nuclear antigen in non-necrotic area went down. The above findings were statistically significant (P < 0.05). These indicate that when the tumor cells re-obtain the well functional exogenic wild-type p53 gene, the gene expresses and produces new negative cell-growth regulator to replace the abnormal regulation system partially, then the growth and proliferation of the tumors can be inhibited; therefore, it is suggested that the p53 tumor suppressor gene may possibly be used as a gene therapy agent to treat oral squamous cell carcinoma.

Animals↗
PubMed1998

[Lecture of principles and applications of capillary electrophoresis (VI) Applications of CE in DNA analysis, carbohydrate analysis and capillary ion analysis].

A review with 87 references on the application and new development of CE in DNA analysis, carbohydrate analysis and capillary ion analysis is presented. The DNA analysis included determinations of nucleotide, nucleoside and bases by CZE and MECC. It also includes dsDNA, PCR products analysis, purity control of oligonucleotide and DNA sequencing by CGE. Sometimes LIF detector needs to be introduced into DNA analysis. The carbohydrate analysis includes the methods for chemical derivatization and direct determination of carbohydrates by different CE modes. The capillary ion analysis includes the principle and determination of anions and cations.

Animals↗
PubMed1998

[Simultaneous analysis of organic acids and inorganic anions in alcoholic drink (dongjiu) by ion chromatography].

An ion chromatographic method for the simultaneous analysis of organic acids and inorganic anions in Dongjiu (alcoholic drink) was developed. An anion exchange column Shim-pack IC-A1(100 mm x 4.6 mm) was used. In non-suppressed anion exchange chromatography, potassium hydrogen phthalate (KHPh) is used as eluent most widely. However, there are several problems in this eluent for the analysis of Dongjiu (alcoholic drink) sample, such as the influence of a negative peak to the determination of acetic acid, ascorbic acid and lactic acid, the non-resolution of ascorbic acid, and lactic acid, and part overlapping of the peak of acetic acid with water peak. In order to solve these problems, a mixed eluent of 0.50 mmol/L KHPh and 0.25 mmol/L phthalic acid(H2Ph) was used in this work. The main organic acids and inorganic anions in Dongjiu were separated without interference peaks. The detection limits obtained by using the mixed eluent were 0.05-0.13 mg/L, several times lower than those obtained by using single KHPh eluent. This method, being without pretreatment, is simple to operate.

Acetic Acid↗
PubMed1998

[Studies on the biological and clinical characteristics of acquired pneumonia caused by K. planticola].

OBJECTIVE: To investigate the characteristics of biological, and clinical epidemiology of acquired pneumonia caused by a new type of Klebsiella, K. planticola. METHOD: 9 strains of K. planticola were isolated from respiratory samples of patients, in vitro, biological and serologic identification were done, in vivo, infected animal models were also evaluated. Clinical epidemiological inquiries were also performed. RESULT: 9 strains' biological features were different from those of the other Klebsiella. The 9 patients' ages were over forty and the primary disease was the third type tuberculosis of lungs. Using of antituberculosis drugs for long term as well as penicillins might be the predisposing factors, corticosteroids were used in 3 of the 9 patients, Combined infection with other pathogens in addition to K. planticola occurred in 8 patients, in 7/8, Candida albicans was identified. Drug sensitive tests show that all of them were resistant to penicillins and sensitive to the second and third generation cephalosporins. CONCLUSION: The new strain of Klebsiella was studied and this information will be useful for diagnosing and treating K. platicola.

Adult↗
PubMed1998

[The testing of local electroretinogram in macular diseases].

OBJECTIVES: To record the local electroretinogram (LERG) in macular diseases, and define the using value of LERG in macular diseases. METHODS: The LERGs of five kinds of maculopathies were recorded with a spot light stimulator at 2.5, 5.0, 7.5 degrees of macular region. RESULTS: (1) The amplitudes of LERG at the three regions in Stargardt's disease, wet form age-related macular degeneration (AMD), central serous chorioretinopathy, and idiopathic macular hole were significantly lowered in comparison with the controls (P < 0.01). In the meanwhile, these diseases also showed high abnormal rates. While in dry form AMD and epiretinal membrane, the amplitudes of LERG had no significant changes (P > 0.05). (2) The abnormal rates of LERG were related to the stimulated area. In the three tested areas, the highest abnormal rates occurred at 2.5 degrees. CONCLUSIONS: There are mean differences in macular electrical activities in these maculopathies. LERG is an effective method of electrophysiology for testing macular function.

Adult↗
PubMed1998

[TLC identification of Flos Carthami].

In 137 kinds of medicinal meterials included 21 kinds of traditional Chinese patent medicines in Pharmacopoeia such as Qili Powder, character identified constituent of Flos Carthami was found by TLC, and was successful to be used to identification of Flos Carthami in 9 kinds of traditional Chinese patent meicines such as Qili Powder.

Carthamus tinctorius↗
PubMed1998

The study of local electrophysiology in macular diseases.

PURPOSES: To observe the features and clinical utility values of local electroretinogram (LERG) and local visual evoked potentials (LVEP) in macular diseases. METHODS: The spot stimuli were obtained by changing the shutters with different sizes of hole at the posterior of Ganzfeld ball. The recording electrode for LERG was made with the filament of platinum as blepharophthalmostat like. The LERG and LVEP were simultaneously recorded in macular diseases. RESULTS: The exudative AMD, Stargardt's disease, central serous chorioretinopathy and idiopathic macular hole had seriously decreased amplitudes of LERG and higher abnormal rates, comparing with atrophic AMD and idiopathic preretinal membranes in the region of 2.5 degrees and 5 degrees at macula. The abnormal rates in these diseases were higher for LERG than for LVEP. CONCLUSION: The LERG can objectively measure the variation of macular function in maculopathies. The sensitivities of LVEP are lower than those of LERG for macular diseases.

Adult↗
PubMed1997

Transcriptional inhibition by Stat5. Differential activities at growth-related versus differentiation-specific promoters.

Prolactin (PRL) induces transcriptional activation of not only growth-related genes such as interferon regulatory factor-1 (IRF-1) but also differentiation-specific genes such as beta-casein through a signaling cascade consisting of Janus kinases and Stat (signal transducer and activator of transcription) factors. To understand better the role of Stats in PRL signaling, we cloned rat Stat5b from a PRL-responsive T cell line Nb2. A Stat5b-specific peptide antibody was generated. In PRL receptor reconstituted COS cells cotransfected with Stat5b or Stat5a, both Stat5 proteins become tyrosine phosphorylated and bind to the IRF-1 GAS (interferon-gamma activation sequence) element in a PRL-inducible manner. Unexpectedly, both Stat5b and Stat5a inhibit PRL induction of the IRF-1 promoter, but they mediate PRL stimulation of the beta-casein promoter. Stat5-mediated inhibition was observed only at the native IRF-1 promoter and not at the isolated IRF-1 GAS element linked to a heterologous thymidine kinase promoter. Mutational analyses showed that the DNA binding activity of Stat5b is not required, but the carboxyl-terminal transactivation domain is essential for Stat5b to inhibit PRL induction of the IRF-1 promoter. These results suggest that Stat5b mediates inhibition via protein-protein interactions. In contrast, both DNA binding and transactivation domains of Stat5b are required to mediate PRL induction of the beta-casein promoter. Furthermore, a carboxyl-terminal truncated dominant negative Stat5b can reverse Stat5b inhibition at the IRF-1 promoter. These studies suggest that Stat proteins can act as not only positive but also negative regulators of gene transcription. Further, Stat5 can modulate gene expression without binding to DNA but via protein-protein interactions.

Amino Acid Sequence↗
PubMed1997

Mapping of the gene (NRAP) encoding N-RAP in the mouse and human genomes.

N-RAP is a nebulin-related actin-binding protein found at the myotendon junction in skeletal muscle and at the intercalated disks in cardiac muscle. We mapped the NRAP gene to mouse chromosome 19 using interspecific crosses and to human chromosome 10 using radiation hybrid panels. Comparative analysis of the mouse and human genomes indicates that the NRAP gene is located in regions of conserved synteny between the two species.

Animals↗