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Q Cai

Publications and source records attributed to Q Cai.

At least 73 records · Page 4Linked to original sources
PubMed1997

Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: in vitro and in vivo studies.

Antisense oligonucleotides are being evaluated in clinical trials as novel therapeutic agents. To further improve the properties of antisense oligonucleotides, we have designed mixed-backbone oligonucleotides (MBOs) that contain phosphorothioate segments at the 3' and 5' ends and have a modified oligodeoxynucleotide or oligoribonucleotide segment located in the central portion of the oligonucleotide. Some of these MBOs indicate improved properties compared with phosphorothioate oligodeoxynucleotides with respect to affinity to RNA, RNase H activation, and anti-HIV activity. In addition, more acceptable pharmacological, in vivo degradation and pharmacokinetic profiles were obtained with these MBOs.

Animals↗
PubMed1997

Singlet oxygen involvement in ultraviolet (254 nm) radiation-induced formation of 8-hydroxy-deoxyguanosine in DNA.

In the present article, we report that ultraviolet (UV 254 nm) radiation substantially induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in purified DNA. The formation of 8-OHdG, a hallmarker of oxidative DNA damage, increased linearly up to 25 kJ/m2 and was dependent on the presence of oxygen in the solution. Deoxygenation by nitrogen significantly reduced the yield of 8-OHdG by UV radiation, whereas oxygenation with 100% oxygen substantially enhanced the yield. The hydroxyl radical (HO.) scavenger dimethysulfoxide (DMSO) dramatically quenched the formation of 8-OHdG by the ionizing radiation and Fenton reaction, but enhanced the formation of UV-induced 8-OHdG. Further studies showed that DMSO and mannitol, two predominant HO. scavengers, enhanced the levels of UV-induced 8-OHdG in a dose-dependent fashion, suggesting that UV-induced 8-OHdG is independent of the generation of HO.. The use of deuterium oxide (D2O), which prolongs the half life of singlet oxygen (1O2), substantially enhanced the yield of 8-OHdG by UV radiation, but not that by Fenton reaction. In contrast, sodium azide, a more and less specific 1O2 quencher, substantially reduced the levels of 8-OHdG by both UV radiation and Fenton reaction, indicating that sodium azide lacks the quenching specificity of 1O2 and HO.. It is proposed that UV induced 8-OHdG proceeds through a singlet oxygen involvement mechanism, rather than the generation of hydroxyl radicals.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1997

A novel RNA species from the turtle mitochondrial genome: induction and regulation of transcription and processing under anoxic and freezing stresses.

The present study identifies a previously cloned cDNA, pBTaR914, as homologous to the mitochondrial WANCY (tryptophan, alanine, asparagine, cysteine, and tyrosine) tRNA gene cluster. This cDNA clone has a 304-bp sequence and its homologue, pBTaR09, has a 158-bp sequence with a long poly(A)+ tail (more than 60 adenosines). RNA blotting analysis using pBTaR914 probe against the total RNA from the tissues of adult and hatchling turtles revealed five bands: 540, 1800, 2200, 3200, and 3900 nucleotides (nt). The 540-nt transcript is considered to be an intact mtRNA unit from a novel mtDNA gene designated WANCYHP that overlaps the WANCY tRNA gene cluster region. This transcript was highly induced by both anoxic and freezing stresses in turtle heart. The other transcripts are considered to be the processed intermediates of mtRNA transcripts with WANCYHP sequence. All these transcripts were differentially regulated by anoxia and freezing in different organs. The data suggest that mtRNA processing is sensitive to regulation by external stresses, oxygen deprivation, and freezing. Furthermore, the fact that the WANCYHP transcript is highly induced during anoxic exposure suggests that it may play an important role in the regulation of mitochondrial activities to coordinate the physiological adaptation to anoxia.

Adaptation, Physiological↗
PubMed1997

Freezing-induced genes in wood frog (Rana sylvatica): fibrinogen upregulation by freezing and dehydration.

Differential screening of a cDNA library produced from liver of the freeze-tolerant wood frog, Rana sylvatica, was used to search for freezing-induced genes. Five freezing-responsive cDNA clones representing different genes were isolated when approximately 80,000 plaques of a cDNA library, prepared from liver of frozen frogs (24 h at -2.5 degrees C), were screened with 32P-labeled total cDNA probes from control (5 degrees C) versus freezing-exposed frogs. Two clones, pBfFR45 and pBfFR04, are reported here in detail and were found to be homologous with the genes for the alpha- and gamma-subunits of fibrinogen, respectively. The clone pBfFR45 carried a 2,305-hp cDNA sequence that was of bipartite structure, containing two open reading frames (ORFs). The first ORF potentially encoded a 332-residue polypeptide, covering a partial sequence of the NH2-terminal region of the alpha-chain. The second ORF encoded a 247-amino acid sequence, covering the whole COOH-terminal region of the alpha-chain; this was highly homologous to the FASORF (fibrinogen-alpha second ORF) of chicken alpha-fibrinogen and the extended alpha-chain of the human protein. Under control (5 degrees C) conditions, moderate levels of fibrinogen alpha- and gamma-transcripts were exclusively found in liver. When frogs were given survivable freezing exposures, levels of these transcripts in liver were highly induced. Transcription of these genes was also elevated in gut and lung during freezing, but mRNA levels in these tissues were lower than in liver. A time course assay confirmed that the transcript levels of both alpha- and gamma-subunit genes were dramatically elevated within the early hours of freezing and reached a maximum threefold increase over control levels after 8 h of freezing exposure. Two other physiological stresses, whole body dehydration and anoxia exposure, mimic individual elements of freezing stress in wood frogs. Northern blot hybridization analysis showed that the expression of both the alpha- and gamma-genes was also upregulated in response to dehydration in vivo (20% of total body water lost), but both were completely inhibited by anoxia exposure.

Amino Acid Sequence↗
PubMed1997

[Role of endothelial-derived nitric oxide and its synthase in the development of hypoxic pulmonary hypertension in rat].

To clarify the role of endothelial-derived nitric oxide (EDNO) and its synthase (NOS) in the normal and hypertensive pulmonary vasculature, activity of endothelial NOS in the lungs, ENDO-dependent vasodilating response induced by bradykinin (BK), and cGMP content of lung tissue in normoxic and hypoxic rats were investigated. We also studied the effects of NOS inhibitor-L-NAME on the activity of NOS, cGMP content, mean pulmonary arterial pressure (mPAP) and carotid systolic arterial pressure (CAPs) in both rats. The results were as follows (1) In normoxic rats there was no NOS activity in the endothelium of small vessels (phi < or = 80 microns) and no relaxing response to BK. Long-term administration of L-NAME obviously inhibited the activity of ecNOS and cGMP content in the lungs of normoxic rats, therefore it led to the increment of CAPs but failed to elevate mPAP. (2) After hypoxic exposure for 10 days, NADPH-diaphorase (NADPH-d and ecNOS immunoreactivity turned to be positive in the endothelium of small vessels with diameter less than 80 microns. BK-induced EDNO-dependent vasodilation, the enzyme activity of cNOS and cGMP content in the lungs of hypoxic rats were significantly enhanced as compared with normoxic rats. Long-term administration of L-NAME in hypoxic rats markedly inhibited the enhancement of cNOS enzyme activity, the production of EDNO and cGMP content in rat lungs, consequently it significantly decreased mPAP but elevated CAPs obviously. These results suggest that the role of EDNO in maintaining the low basal tone of normal adult pulmonary circulation remain to be studied more precisely. The increased activity of ecNOS and the enhancement of EDNO synthesis might act to moderate the hypertension. The excess synthesis of EDNO might be toxic to the endothelium of pulmonary vessels, therefore potentiating the development of pulmonary hypertension.

Animals↗
PubMed1997

[Antiepileptic effects of nimodipine on penicillin-induced seizures in rats].

Injecting penicillin (PNC) intraperitoneally in Wistar rats, we observed their epileptic behaviour and electroencephalographys. The results showed that nimodipine (NIM), a calcium antagonist, could inhibit the seizures and epileptic discharges significantly. No epileptic action was noted while NIM was injected before PNC. It supports our consideration of NIM as a new sort of nonsedative anticonvulsant in clinical practice.

Animals↗
PubMed1997

[Study on the molecular epidemiology of diarrhea caused by enterotoxigenic Escherichia coli, using polymerase chain reaction with multiple primer pairs].

A Polymerase Chain Reaction (PCR) method has been developed for detecting Enterotoxigenic Escherichia coli (ETEC). Three different sets of oligonucleotide primer were simultaneously used to amplify the enterotoxin genes of heat-labile (LTh) and heat-stable (STIa and STIb) enterotoxins of ETEC. These primers amplified the 627, 240 or 169 base pair DNA fragments from LTh, STIa and STIb genes of the reference ETEC strains, respectively. Five types of ETEC strains corresponding to the LTh, STIa, STIb, LTh-STIa, or LTh-STIb genotypes were distinguished by a single procedure of PCR, using the mixture of the three sets of primers. There was no cross-reaction with the non-ETEC strains. The lowest detection level was 10 cfu. A total number of 623 stool specimens of diarrheal patients from Shangdong Province induced by E. coli were examined by PCR and the positive rate of ETEC was 40.3%. The results indicated that PCR is a rapid, sensitive and specific method for detecting ETEC.

China↗
PubMed1996

Anoxia-induced gene expression in turtle heart. Upregulation of mitochondrial genes for NADH-ubiquinone oxidoreductase subunit 5 and cytochrome c oxidase subunit 1.

A cDNA library constructed from heart of anoxia-exposed adult turtles (Trachemys scripta elegans) was differentially screened with 32P-labeled single-stranded cDNA probes from heart of control versus anoxic animals to clone genes induced by anoxia stress. Four cDNA clones, pBTaR20, pBTaR34, pBTaR63 and pBTaR914 were obtained and confirmed to be upregulated in response to anoxic submergence (20 h in N2-bubbled water at 7 degrees C). Two clones, pBTaR20 and pBTaR63, were characterized by sequence analysis and in vivo expression. The clone pBTaR20 had a 1597-bp cDNA sequence and pBTaR63 contained a 1837-bp sequence. The pBTaR20 sequence contained a single open reading frame that was very close to full length and could potentially encode a polypeptide with 508 amino acids. The deduced polypeptide sequence showed approximately 83% of the residues identical with the sequence of cytochrome c oxidase subunit 1 (CO1) that is encoded by a mtDNA gene Cox1. The clone pBTaR63 contained a single potentially full-length open reading frame that could encode a polypeptide of 591 residues. This was similar to another mitochondrial protein, NADH-ubiquinone oxidoreductase subunit 5 (ND5), which is encoded by mtDNA gene Nad5. Analysis of the time course of expression of Cox1 and Nad5 by northern hybridization analysis showed that mRNA transcripts for both accumulated rapidly (within 1 h) in response to anoxia exposure. Both showed similar increases in their transcript content after 1 h of anoxia but with longer anoxia exposures (5 or 20 h) Nad5 mRNA levels remained high whereas Cox1 mRNA content declined somewhat. Northern-blot hybridization also revealed differential expression of these two genes in five other organs of T. s. elegans during anoxia exposure (brain, kidney, liver, red and white skeletal muscle), with a particularly large increase in mRNA transcript levels of both genes in anoxic red muscle. Organ-specific analysis of these genes in a freeze-tolerant turtle species (Chrysemys picta marginata) also showed that differential expression of these genes occurred in response to the ischemia induced by plasma freezing.

Amino Acid Sequence↗
PubMed1996

Mechanism of the systemic, left ventricular, and coronary vascular tolerance to a binge of cocaine in conscious dogs.

BACKGROUND: Prior experimental studies have emphasized the cardiovascular effects of acute, single doses of cocaine. However, cardiovascular complications are most often reported in chronic users, who have been exposed to repetitive doses of cocaine. It remains unclear whether there is tolerance or sensitization to the systemic, left ventricular, and coronary hemodynamic effects of a binge of cocaine. METHODS AND RESULTS: We studied 11 conscious, chronically instrumented dogs to determine the systemic pressor, inotropic, chronotropic, and coronary vascular resistance responses to cocaine (1 mg/kg IV) administered every 25 minutes for five doses. There was progressive tolerance to the systemic pressor (mean arterial pressure: first dose, +42 +/- 4% from 97 +/- 2 mm Hg; fifth dose, +8 +/- 3% from 116 +/- 7 mm Hg; P < .01) and heart rate (first dose, +45 +/- 8% from 93 +/- 5 bpm; fifth dose, +8 +/- 2% from 109 +/- 9 bpm; P < .01) responses and abolition of the positive inotropic (left ventricular dP/dt: first dose, +19 +/- 4% from 2824 +/- 75 mm Hg/s; fifth dose, -3 +/- 5% from 2531 +/- 436 mm Hg/s; P < .01) and coronary vasoconstrictor (coronary vascular resistance: first dose, +38 +/- 9% from 1.9 mm Hg.mL-1.min-1; fifth dose, -7 +/- 2% from 2.6 +/- 0.2 mm Hg. mL-1.min-1; P < .01) responses to a binge of cocaine despite progressive increases in peak plasma cocaine concentrations. In contrast, both the plasma norepinephrine and epinephrine responses were attenuated with repetitive exposure to cocaine, whereas myocardial alpha and beta-adrenergic responsiveness was maintained. CONCLUSIONS: Repetitive cocaine administration is associated with the development of early and progressive tolerance to systemic, left ventricular, and coronary vascular effects of cocaine. The mechanism of the tolerance involves neither impaired myocardial nor coronary vascular responsiveness to adrenergic stimulation but, rather, attenuated catecholamine responses to repetitive cocaine administration.

Animals↗
PubMed1996

Kinetic assay of antitrypsin in human serum by a surface acoustic wave(SAW)-impedance sensor.

Antitrypsin in human serum was determined by using both the SAW-impedance sensor system and spectrophotometry, indicating that the mean value for women was significantly higher than the mean value for men; the value for acute pancreasis patients is about 2-folds of the normal values, and there is no significant difference between the acute pancreasis patients and the pancreatic cancer patients.

Journal Article↗
PubMed1996

Effect of dietary genistein on antioxidant enzyme activities in SENCAR mice.

Dietary administration of the soybean isoflavone genistein (50 and 250 ppm) for 30 days significantly increases the activities of antioxidant enzymes in various organs of SENCAR mice. Feeding a 250-ppm genistein diet to SENCAR mice significantly increases the activities of catalase in small intestine, liver, and kidney, the activities of superoxide dismutase and glutathione peroxidase in skin, and the activity of glutathione reductase in skin and small intestine. Feeding 50 ppm genistein to SENCAR mice results in elevated catalase activity in the small intestine and increases glutathione-S-transferase activities in skin, small intestine, liver, kidney, and lung. Dietary genistein's greatest enhancement of antioxidant enzyme activities occurred in skin and small intestine. Our results suggest that dietary genistein enhances the activities of antioxidant enzymes in various organs, which may be a mechanism(s) of genistein's chemopreventive action.

Animals↗
PubMed1996

Inhibition of UV light- and Fenton reaction-induced oxidative DNA damage by the soybean isoflavone genistein.

We have investigated the effect of the soybean isoflavone genistein on 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in calf thymus DNA exposed to either UV irradiation or the Fenton reaction system. Under the conditions used we observed that UV light and the Fenton reaction significantly increase 8-OHdG formation in DNA. Co-incubation with genistein inhibits the formation of 8-OHdG induced by either UV light irradiation or the Fenton reaction in a dose-dependent manner. The quenching effect of genistein on 8-OHdG formation induced by UV light is much more potent than that by the Fenton reaction, suggesting that the mechanisms of 8-OHdG formation may differ between the two systems. We further compared the antioxidant activities and quenching effect on 8-OHdG formation of genistein with biochanin A. Genistein potently scavenges both hydrogen peroxide in the medium and superoxide anion generated by xanthine/xanthine oxidase, whereas biochanin A has either a weak or no scavenging effect on these reactive oxygen species. However, both genistein and biochanin A display a similar quenching effect on UV light-induced 8-OHdG formation. These results suggest that the quenching effect of genistein and biochanin A on UV light-induced 8-OHdG formation is different from their ability to scavenge hydrogen peroxide and superoxide anion. The potent inhibition of UV light-induced oxidative DNA damage by genistein suggests its potential anticarcinogenic role in photocarcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

Detection of cytosine methylation and mapping of a gene influencing cytosine methylation in the genome of Citrus.

A new method was developed to detect DNA methylation in the Citrus genome using random amplification coupled with restriction enzyme digestion. Genomic DNA from Citrus grandis (L.) Osb., Poncirus trifoliata (L.) Raf., and their F1 hybrid was amplified using 7 individual 10-mer random primers. Prior to amplification the DNA templates were digested with 2 pairs of restriction endonucleases (HpaII-MspI and (or) Sau3AI-NdeII) with different sensitivities to cytosine methylation and after PCR amplification their amplified products were further digested with the same enzymes. Using this method, it was possible to detect 28 methylation events involving 23 amplified bands with the 7 random primers and 2 pairs of enzymes. A methylation polymorphism was found at a Sau3AI site in a 1.2-kb band amplified with one primer. One locus influencing cytosine methylation at this restriction site was identified through genetic analysis of a BC1 population between C. grandis and P. trifoliata and was mapped to linkage group IV using an already developed core map. This technique for detecting methylation and methylation polymorphisms is simple and should be applicable to any eukaryotic species and to many situations where it is desirable to determine whether a sequence is methylated.

Base Sequence↗
PubMed1995

In vivo formation of DNA-adducts in mouse skin DNA by tamoxifen.

Tamoxifen (TAM)-induced DNA adduct formation in mouse skin was determined by a nuclease P1-enhanced 32P-postlabelling technique. Topical application of TAM significantly induced a number of DNA-adducts in mouse skin in a dose- and time-dependent manner. When SENCAR mice were topically treated with different doses of TAM for 6 h, total DNA adduct levels in skin were increased by 2.5- (1 mumol TAM), 4.5- (5 mumol TAM) and 4.8-fold (10 mumol TAM), respectively. In addition, at least four novel DNA adducts were observed. Time-course studies showed that TAM-induced DNA adducts reach a peak at 6 h post-treatment. However, the pattern of TAM-induced DNA adducts was different from that induced by DMBA (a potent skin carcinogen). TAM has been found to form DNA-adducts in the liver and kidney of rodents. Our work confirms the genotoxic effects observed by other investigators by showing that TAM also causes DNA-adducts formation in mouse skin. Since TAM is widely used for the treatment of breast cancer and currently for chemo-prevention trials, further studies should be conducted to assess the potential risk of long-term use of TAM in humans.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

An unusual group 2 LEA gene family in citrus responsive to low temperature.

Six cDNAs representing unique cold-induced sequences have been cloned from the hardy citrus relative Poncirus trifoliata. Among these, pBCORc115 and pBCORc119 were found to belong to the same gene family. Sequencing data indicated that pBCORc115 and pBCORc119 each contained an open reading frame, coding for a 19.8 kDa protein (COR19) and a smaller 11.4 kDa protein (COR11) respectively. Inspection of the deduced amino acid sequences revealed three large repeats in COR19, but only one was present in the COR11. Two elements: a Q-clustered tract and a K-rich motif were identified in each repeat. The K-rich motifs were similar to those of cotton D-11 and Group 2 LEA proteins. A Serine-cluster, a common feature in many Group 2 LEA-like proteins, was also found in these proteins, but it was in an unusual position at the carboxy-terminus. A bipartite motif of basic residues, similar to known nuclear targeting sequences, was also present in COR19 and COR11, suggesting that members of this protein family may have a nuclear targeting function. The expression of COR19 mRNA in response to cold acclimation, drought, flooding, and salinization was examined. COR19 expression in leaf tissue was induced in response to cold acclimation, but repressed during drought and flooding stress.

Adaptation, Physiological↗