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Biomedical subjects

L Q Tang

Publications and source records attributed to L Q Tang.

13 recordsLinked to original sources

Bioreductive metabolism of mitomycin C in EMT6 mouse mammary tumor cells: cytotoxic and non-cytotoxic pathways, leading to different types of DNA adducts. The effect of dicumarol.

The six DNA adducts formed in EMT6 mouse mammary tumor cells upon treatment with mitomycin C (MC) fall into two groups: (1) four guanine adducts of MC and (2) two guanine adducts derived from 2,7-diaminomitosene (2,7-DAM), the major reductive metabolite of MC. The two groups of adducts were proposed to originate from two pathways arising from reductive activation of MC: (a) direct alkylation of DNA and (b) formation of 2,7-DAM, which then alkylates DNA. The aim of this study was to test the validity of this proposal and to evaluate the significance of alkylation of DNA by 2,7-DAM. Treatment of the cells with 2,7-DAM itself yielded the same 2,7-DAM-guanine adducts as treatment with MC; however, 2,7-DAM was approximately 100-fold less cytotoxic than MC. The uptake and efflux of 2,7-DAM by EMT6 cells was comparable to that of MC, but 2,7-DAM alkylated DNA with higher efficiency than MC. These results validate the two proposed pathways and show that formation of 2,7-DAM-DNA adducts in MC-treated cells represents a relatively non-toxic pathway of reductive metabolism of MC. A selective stimulatory effect of dicumarol (DIC) on 2,7-DAM-DNA adduct formation in EMT6 cells treated with MC was also investigated. DIC had no effect on alkylation by MC in cell-free systems, nor did it have significant effects on adduct formation or cell survival for cells treated with 2,7-DAM. It is proposed that in the cell DIC stimulates a reductase enzyme located at subcellular sites where the activated MC species has no direct access to DNA and therefore is diverted into the non-cytotoxic pathway, which leads to the formation of 2,7-DAM and its adducts.

Animals↗

Prenatal hypoxia impairs the postnatal development of neural and functional chemoafferent pathway in rat.

1. To define the effects of prenatal hypoxia on the postnatal development of the chemoafferent pathway, ventilation and metabolism, pregnant rats were exposed to normobaric hypoxia (10 % oxygen) from embryonic day 5 to embryonic day 20. Offspring were studied at 1, 3 and 9 weeks of age in three separate protocols. 2. Prenatal hypoxia decreased the dopamine content in the carotid bodies at all ages, and decreased the utilisation rate of noradrenaline in the caudal part of the A2 (A2c), A1 and A5 noradrenergic brainstem cell groups at 3 weeks after birth. At 9 weeks of age, the level of dopamine in the carotid bodies was still reduced but the utilisation rate of noradrenaline was enhanced in A1. 3. Rats from dams subjected to hypoxia during pregnancy hyperventilated until 3 weeks after birth. In these rats, the biphasic hypoxic ventilatory response was absent at 1 week and the increase in minute ventilation was amplified at 3 weeks. 4. Prenatal hypoxia disturbed the metabolism of offspring until 3 weeks after birth. A weak or absent hypometabolism in response to hypoxia was observed in these rats in contrast to control animals. 5. Prenatal hypoxia impairs the postnatal development of the chemoafferent pathway, as well as the ventilatory and metabolic responses to hypoxia. These alterations were mostly evident until 3 weeks after birth.

3,4-Dihydroxyphenylacetic Acid↗

C-fos gene expression in rat brain around birth: effect of asphyxia and catecholamines.

At birth, the mammalian nervous system must adapt rapidly to the new conditions it encounters in the extra-uterine environment. One aspect of this adaptation, known as arousal, is mediated by catecholamines, the levels of which in the brain increase rapidly after birth. The pattern of gene expression also changes. Shortly after birth, expression of the immediate early gene c-fos, known to reflect general neural activity, is up-regulated. Furthermore, asphyxia often occurs in connection with birth. In order to examine the effects of this phenomenon on the expression of c-fos, as well as on the rate of noradrenaline (NA) turnover, asphyxia was induced in rat pups delivered by caesarean section. Northern blot analysis and in situ hybridization revealed that the increase in expression of c-fos in certain areas of the brain was greatly enhanced by asphyxia of moderate duration; whereas more prolonged asphyxia lowered the level of c-fos mRNA. Asphyxia had a similar effect on the rate of NA turnover. Adrenergic receptor antagonists administered prior to birth attenuated the birth-related induction of c-fos mRNA. However, the potentiation of c-fos expression by asphyxia was not altered by these antagonists. Therefore, we propose that while catecholamines play an important role in the induction of c-fos in the brain at birth, the effects of asphyxia involve a different mechanism.

Adrenergic Antagonists↗

Maternal caffeine intake has minor effects on adenosine receptor ontogeny in the rat brain.

Maternal caffeine intake has been suggested to influence the offspring. We have studied the effects of maternal caffeine intake on adenosine and GABA receptors, targets for caffeine, during development of the rat brain. Caffeine (0.3 g/L) was added to the drinking water of rat dams during pregnancy and early postnatal life. Adenosine A1 and A2A and GABAA receptor development was studied using receptor autoradiography and in situ hybridization. Pups were examined on embryonic d 14 (E14), E18, E21, 2 h after birth (P2h), P24h, postnatal d 3 (P3), P7, P14, and P21. Adenosine A, receptor mRNA was detected at E14 and receptors at E18. A1 mRNA levels increased from the level reached at E18 between P3 and P14 (maximally a doubling), whereas A, receptors, studied by [3H]-1,3-dipropyl-8-cyclopentyl xanthine binding, increased later and to a much larger extent (about 10-fold) postnatally. Caffeine treatment had no significant effect on adenosine A1 receptors or on A1 receptor mRNA. A2A mRNA had reached adult levels by E18, whereas receptor levels were low or undetectable before birth and increased dramatically until P14. Caffeine did not influence A2A receptors or A2A receptor mRNA at any stage during development. [3H]-flunitrazepam binding, representing GABAA receptors, showed large regional variations during ontogeny, but there were no clear differences between the caffeine-exposed and the nonexposed pups. Thus, exposure to a low dose of caffeine during gestation and postnatal life had only minor effects on development of adenosine A, and A2A receptors and GABAA receptors in the rat brain.

Adenosine↗

Combination of systemic acetazolamide and topical dorzolamide in reducing intraocular pressure and aqueous humor formation.

OBJECTIVE: The study aimed to determine whether topical dorzolamide and systemic acetazolamide have an additive effect on intraocular pressure (IOP) and aqueous humor formation (AHF). DESIGN: This was a prospective, open-label, two-protocol clinical study. PARTICIPANTS: Sixteen patients with ocular hypertension or with primary open-angle glaucoma were studied. INTERVENTION: Baseline AHF was measured by computerized fluorophotometry and IOP by pneumatonometry without antiglaucoma therapy. In the first protocol, dorzolamide was randomized to one eye (N = 10) and IOP and AHF measurements were repeated. One week later, having used dorzolamide in one eye three times daily, patients had measurements performed before and after the single administration of oral acetazolamide 250 mg. In the second protocol, having used acetazolamide 250 mg four times daily for 4 to 7 days (N = 6), patients had measurements performed before and after a single drop of dorzolamide was instilled randomly into one eye. The patient continued acetazolamide and unilateral dorzolamide for 4 to 7 more days and returned for IOP and AHF measurements. MAIN OUTCOME MEASURES: Intraocular pressure and AHF were measured in treated and contralateral control eyes. RESULTS: In the first protocol, IOP (mmHg +/- standard deviation) was significantly (P = 0.02) lower in the dorzolamide (16.3 +/- 2.6) than in the contralateral control (19.9 +/- 2.9) eyes. Aqueous humor formation (microliter/minute +/- standard deviation) also was lower (P = 0.02) in dorzolamide eyes (1.79 +/- 0.4 vs. 2.33 +/- 0.5). After oral acetazolamide 250 mg, IOP was unchanged in dorzolamide eyes (17.6 +/- 2.0 preacetazolamide vs. 17.9 +/- 2.0 postacetazolamide), whereas it was reduced (P = 0.003) in control eyes (20.5 +/- 2.2 preacetazolamide vs. 16.9 +/- 2.3 postacetazolamide). Aqueous humor formation was reduced in control eyes (2.31 +/- 0.8 preacetazolamide vs. 1.73 +/- 0.6 postacetazolamide; P = 0.005) but not in dorzolamide-treated eyes (1.56 +/- 0.45 preacetazolamide vs. 1.77 +/- 0.39 postacetazolamide). In the second protocol, acetazolamide 250 mg four times daily symmetrically reduced IOP and AHF in both eyes. After single-drop dorzolamide in one eye, IOP and AHF did not change significantly. After 4 to 7 days of acetazolamide and unilateral dorzolamide, IOP and AHF remained reduced to a similar level in dorzolamide and control eyes not receiving topical therapy. CONCLUSION: Topical dorzolamide and oral acetazolamide, in the concentrations and doses used in this study, are not additive. Either drug alone results in maximum reduction in IOP and AHF. Concomitant glaucoma therapy of a topical and systemic carbonic anhydrase inhibitor is not warranted.

Acetazolamide↗

Effect of beta-adrenergic agents on intracellular potential of rabbit ciliary epithelium.

PURPOSE: To study the effects of beta-adrenergic agents on intracellular potential (Vm) of the isolated and intact rabbit ciliary epithelium. METHODS: Vm was measured on the isolated intact ciliary epithelium superfused with adrenergic agents and cyclic AMP modulators. RESULTS: The nonselective beta-adrenergic agonist isoproterenol depolarized Vm in a dose-dependent fashion. beta-adrenergic antagonists alone had no effect on baseline Vm. The isoproterenol response was blocked by the nonselective antagonist timolol (5 x 10(-5) M). The selective beta 2-antagonist ICI 118-551 caused a greater inhibition (IC50 approximately 7 x 10(-7)) than the selective beta 1-antagonist betaxolol (IC50 approximately 6 x 10(-6)). The isoproterenol response was also significantly (p < 0.03) blocked by the non-selective alpha-antagonist phentolamine. Cyclic AMP and phosphodiesterase inhibitors significantly decreased Vm. Pretreatment with these inhibitors potentiated the agonist-induced depolarization. Barium, a blocker of Ca(2+)-sensitive K+ channels, significantly decreased baseline Vm. Barium pretreatment blocked the beta-agonist and cAMP induced depolarization of Vm, suggesting that the K+ current is necessary for the observed isoproterenol response. Pretreatment with the cotransport inhibitor bumetanide had no effect on the isoproterenol-induced response. CONCLUSIONS: The beta-adrenergic agonist isoproterenol affects ionic transport processes across the ciliary epithelium (beta 2 > beta 1). This effect is likely mediated through adenylate cyclase coupled to adrenoreceptors and requires the presence of the K+ current. Blockage of the isoproterenol-induced decrease in Vm by a nonselective alpha-adrenergic antagonist indicates an interaction between the two adrenergic systems in the ciliary epithelium.

Adenylyl Cyclases↗

[Epidemiological trend and its impact on malaria control programme in Shenzhen from 1950-1995].

Shenzhen has been developed as the first economic special zone in China. Two large scale outbreaks of vivax malaria have occurred in the history. Anopheles anthropophagus has been identified as the major vector. For the last 45 years, we have adopted an effective measure for malaria control based on the epidemiological characteristics in different period. As a result, the morbidity rate of malaria has been under control given the condition of social and economy development and the big increase of mobile population.

Animals↗

Expression of c-fos, tyrosine hydroxylase, and neuropeptide mRNA in the rat brain around birth: effects of hypoxia and hypothermia.

Arousal at birth is likely to be accompanied by changes in gene expression patterns in the brain. We analyzed the expression levels of genes that may be involved in neonatal adaptation. We have also tried to dissect the effect of hypoxia and hypothermia, two components that may play a role in gene expression at birth. Therefore, we analyzed the expression patterns of the c-fos, tyrosine hydroxylase, enkephalin, preprotachykinin-A, and neuropeptide Y genes in various brain regions of rat pups at various time points after cesarean section under normal conditions and after exposure to hypoxia and hypothermia. We found that c-fos RNA was up-regulated transiently after birth in neocortex, midbrain, and pons-medulla with a maximum of 30 min after cesarean section, and that this transient increase was not further augmented by hypoxia and hypothermia. The expression patterns of the other genes were not significantly altered, with the exception of a very slight increase in tyrosine hydroxylase RNA levels. We discuss tentative mechanisms for the transient increase in c-fos expression and the possible involvement of catecholamines in this process.

Animals↗

Dye coupling of rabbit ciliary epithelial cells in vitro.

PURPOSE: To examine the in vitro properties of gap junctions on the isolated rabbit ciliary epithelium. METHODS: Intracellular potential was measured and lucifer yellow (5% in 1 M LiCl) was iontophoretically injected into a ciliary epithelial cell. Fixated tissue was examined with a laser confocal microscope. RESULTS: Dye spread was observed throughout both layers (horizontally and vertically) of the ciliary epithelium adjacent to the injected cell that was more intensely labeled. Dye reflux did not occur at the site of microimpalement. Microiontophoretic dye injection in a bathing solution with a high Ca2+ (10 mM) or an acidic pH (6.3) completely inhibited cell-cell dye coupling in the rabbit ciliary epithelial cells. CONCLUSIONS: Laser confocal microscopy of intracellularly injected lucifer yellow dye demonstrates the physiologic presence of gap junctions between both ciliary epithelial layers. Extracellular acidosis and high concentration of extracellular Ca2+ cause loss of cell-cell coupling in the rabbit ciliary epithelium.

Animals↗

Halogenated inhalation anesthetic agents decrease transepithelial electrical measurements across the isolated iris-ciliary body.

Transmembrane electrical measurements were performed on the isolated rabbit iris-ciliary body (I-CB) to study the direct effects of halogenated inhalation anesthetic agents on the ciliary epithelium. Addition of either halothane, enflurane, or isoflurane to the control 95% O2:5% CO2 gas mixture resulted in a dose-dependent decrease in the short-circuit current (SCC) and potential difference (PD). This response was reversible after the anesthetic gas was discontinued. Pretreatment with either alpha-adrenergic or beta-adrenergic antagonists (phentolamine or timolol) had no effect on the halothane-induced decrease in SCC. Delivery of the analgestic gas N2O did not alter baseline electrical measurements across the isolated I-CB.

Analysis of Variance↗

Prevalence of age-related cataract in Ganzi and Shanghai. The Epidemiological Study Group.

It has been reported that the prevalence of cataract is much higher in plateau than that in plain regions. But the data are incomplete and can not be compared because of different examination methods and different diagnostic criteria. A small group of ophthalmologists was sent to Ganzi, Sichuan Province at the altitude of 3.393 m, and to Qinpu in the suburb of Shanghai which is at the sea level. In Ganzi 3,905 (91.97%) people including 822 Hans and 3,083 Zang and in Qinpu 3,101 (93.20%) were studied. Age-related cataract was diagnosed when there are cortical or nuclear, or mixed opacities; and aphakia due to previous extraction of age-related cataract. Direct method was used to standardize the data. The prevalence of age-related cataract in Ganzi is about 82% higher than that in Qinpu in all age groups; from age 16-60, the prevalence of age-related cataract in Ganzi is about 180% (in Hans) and 160% (in Zangs) higher than that in Qinpu. There is no significant difference in the prevalence of age-related cataract between the ethnic groups in Ganzi. In Ganzi, the sunshine hours per year are 1.28 times that in Qinpu, and the global radiation in Ganzi is 1.47 times that in Qinpu. The higher prevalence of cataract in Ganzi than in Qinpu may be due to the greater exposure to the sunshine on the Tibetan plateau. The differences in prevalence between males and females and between indoor and outdoor work are discussed.

Adolescent↗