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Biomedical subjects

Z Xie

Publications and source records attributed to Z Xie.

At least 91 records · Page 5Linked to original sources

Oligomerization of dopamine and serotonin receptors.

Until recently, it has largely been assumed that G protein-coupled receptors (GPCRs) function as monomeric entities. However, over the past few years, we and others have documented that GPCRs can form dimers and oligomers, leading to a re-evaluation of the mechanisms thought to mediate GPCR function. Despite the growing number of investigations into dimerization, little is known about the structural basis of receptor-receptor interactions and the functional consequences of dimer formation. Here, we present a brief review of some insights we have gained into the dimerization of dopamine and serotonin receptors. We have demonstrated that agonist-regulated trafficking is identical for receptor monomers and dimers, however, agonist treatment appears to stabilise the receptor oligomers. An investigation of the structural assembly between receptors involved in dimerization showed that there are several sites of interaction including hydrophobic transmembrane domain interactions and intermolecular disulphide bonds. We have also examined receptor hetero-oligomerization and demonstrated the potential for novel functions as a result of these associations. Finally, as a result of these observations, we have been able to present evidence that GPCRs function as oligomers in the cell.

Animals↗

Regulation of Na/K-ATPase beta1-subunit gene expression by ouabain and other hypertrophic stimuli in neonatal rat cardiac myocytes.

Partial inhibition of Na/K-ATPase by ouabain causes hypertrophic growth and regulates several early and late response genes, including that of Na/K-ATPase alpha3 subunit, in cultured neonatal rat cardiac myocytes. The aim of this work was to determine whether ouabain and other hypertrophic stimuli affect Na/K-ATPase beta1 subunit gene expression. When myocytes were exposed to non-toxic concentrations of ouabain, ouabain increased beta1 subunit mRNA in a dose- and time-dependent manner. Like the alpha3 gene, beta1 mRNA was also regulated by several other well-known hypertrophic stimuli including phenylephrine, a phorbol ester, endothelin-1, and insulin-like growth factor, suggesting involvement of growth signals in regulation of beta1 expression. Ouabain failed to increase beta1 subunit mRNA in the presence of actinomycin D. Using a luciferase reporter gene that is directed by the 5'-flanking region of the beta1 subunit gene, transient transfection assay showed that ouabain augmented the expression of luciferase. These data support the proposition that ouabain regulates the beta1 subunit through a transcriptional mechanism. The effect of ouabain on beta1 subunit induction, like that on alpha3 repression, was dependent on extracellular Ca2+ and on calmodulin. Inhibitions of PKC, Ras, and MEK, however, had different quantitive effects on ouabain-induced regulations of beta1 and alpha3 subunits. The findings show that partial inhibition of Na/K-ATPase activates multiple signaling pathways that regulate growth-related genes, including those of two subunit isoforms of Na/K-ATPase, in a gene-specific manner.

Adenoviridae↗

Experimental study on skin sensitization potencies and cross-reactivities of hair-dye-related chemicals in guinea pigs.

In screening patch testing of hairdressers with occupational contact dermatitis, multiple positive reactions to hair dye-related chemicals, such as p-phenylenediamine (PPD), p-toluenediamine x 2HCl (PTD) and p-aminophenol (PAP), a fabric dye p-aminoazobenzene (PAB), and a tar dye Sudan III, were frequently encountered. To investigate individual skin sensitization potency and the cross-reactivities among above chemicals, a guinea pig maximization test with the above 5 chemicals was performed. In each group, 6 animals were induced with one of the chemicals at 0.1% concentration by intradermal injection and at 1.0% by topical application. The animals were challenged with all 5 chemicals in concentrations of dilution by 10 from 0.1% to 0.001%. Under the conditions of 0.1% challenges, similar sensitization potencies were observed in PPD (6/6), PTD (6/6), PAP (5/6) and PAB (6/6) groups, but no positive reactions were elicited in the Sudan III group. The cross-reactivities to PPD were confirmed in the animals challenged with PTD (6/6), PAP (6/6), PAB (6/6) and Sudan III (3/6). In the PTD-induced group, positive responses to cross-challenges were elicited by PPD (5/6), PAP (3/6), PAB (5/6) and Sudan III (1/6). The cross-reactivities to PAP were observed only with PPD (2/5) and PAB (5/5). PAB-induced animals responded only to PPD (1/6). The results indicate that all these chemicals except Sudan III are strong sensitizers. Their cross-reactivities are different in sensitized conditions, respectively. The cross-reactivities to PPD were higher than those to PTD, PAP and PAB.

Aminophenols↗

Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy.

The time at which ovarian failure (menopause) occurs in females is determined by the size of the oocyte reserve provided at birth, as well as by the rate at which this endowment is depleted throughout post-natal life. Here we show that disruption of the gene for acid sphingomyelinase in female mice suppressed the normal apoptotic deletion of fetal oocytes, leading to neonatal ovarian hyperplasia. Ex vivo, oocytes lacking the gene for acid sphingomyelinase or wild-type oocytes treated with sphingosine-1-phosphate resisted developmental apoptosis and apoptosis induced by anti-cancer therapy, confirming cell autonomy of the death defect. Moreover, radiation-induced oocyte loss in adult wild-type female mice, the event that drives premature ovarian failure and infertility in female cancer patients, was completely prevented by in vivo therapy with sphingosine-1-phosphate. Thus, the sphingomyelin pathway regulates developmental death of oocytes, and sphingosine-1-phosphate provides a new approach to preserve ovarian function in vivo.

Animals↗

Conserved amino acids at the C-terminus of rat phospholipase D1 are essential for enzymatic activity.

Rat brain phospholipase D1 (rPLD1) has two highly conserved motifs [H(X)K(X)4D, denoted HKD] located at the N-terminal and C-terminal halves, which are required for activity. Association of the two halves is essential for rPLD1 activity, which probably brings the two HKD domains together to form a catalytic center. In the present study, we find that an intact C-terminus is also essential for the catalytic activity of rPLD1. Serial deletion of the last four amino acids, EVWT, which are conserved in all mammalian PLD isoforms, abolished the catalytic activity of rPLD1. This loss of catalytic activity was not due to a lack of association of the N-terminal and C-terminal halves. Mutations of the last three amino acids showed that substitutions with charged or less hydrophobic amino acids all reduced PLD activity. For example, mutations of Thr1036 and Val1034 to Asp or Lys caused marked inactivation, whereas mutation to other amino acids had less effect. Mutation of Trp1035 to Leu, Ala, His or Tyr caused complete inactivation, whereas mutation of Glu1033 to Ala enhanced activity. The size of the amino acids at the C-terminus also affected the catalytic activity of PLD, reduced activity being observed with conservative mutations within the EVWT sequence (such as T/S, V/L or W/F). The enzyme was also inactivated by the addition of Ala or Val to the C-terminus of this sequence. Interestingly, the inactive C-terminal mutants could be complemented by cotransfection with a wild-type C-terminal half to restore PLD activity in vivo. These data demonstrate that the integrity of the C-terminus of rPLD1 is essential for its catalytic activity. Important features are the hydrophobicity, charge and size of the four conserved C-terminal amino acids. It is proposed that these play important roles in maintaining a functional catalytic structure by interacting with a specific domain within rPLD1.

Amino Acids↗

Effects of hypokalemia on cardiac growth.

In neonatal myocytes grown in culture, reductions in extracellular potassium concentration produced a hypertrophic response as assessed by induction of early response genes, atrial natriuretic peptide and skeletal actin, and repression of the alpha3 isoform of the sodium pump in a dose dependent manner. The degree of alpha3 repression appeared to be dose dependent with decreases in media (K). Similarly, decreases in media potassium concentrations caused increases in cytosolic calcium concentration in a dose dependent manner; moreover these increases in cytosolic calcium concentration correlated quite well with repression of alpha3 expression. In contrast, although moderate reductions of potassium concentration induced upregulation of skACT and ANP, severely reduced potassium concentrations caused repression of skACT and ANP expression. In parallel studies performed in vivo, 3-5 weeks dietary K restriction induced molecular phenotypical changes similar to that seen in the neonatal myocyte model without demonstrable growth as assessed by the heart weight/body weight ratio. However, when rates subjected to dietary K restriction were subsequently subjected to acute aortic constriction, cardiac growth was greater than in rats fed a control diet. These data suggest that hypokalemia may produce molecular phenotypic alterations consistent with cardiac hypertrophy as well as contribute to hypertrophy in an in vivo model.

Animals↗

Identification of a novel family of nonclassic yeast phosphatidylinositol transfer proteins whose function modulates phospholipase D activity and Sec14p-independent cell growth.

Yeast phosphatidylinositol transfer protein (Sec14p) is essential for Golgi function and cell viability. We now report a characterization of five yeast SFH (Sec Fourteen Homologue) proteins that share 24-65% primary sequence identity with Sec14p. We show that Sfh1p, which shares 64% primary sequence identity with Sec14p, is nonfunctional as a Sec14p in vivo or in vitro. Yet, SFH proteins sharing low primary sequence similarity with Sec14p (i.e., Sfh2p, Sfh3p, Sfh4p, and Sfh5p) represent novel phosphatidylinositol transfer proteins (PITPs) that exhibit phosphatidylinositol- but not phosphatidylcholine-transfer activity in vitro. Moreover, increased expression of Sfh2p, Sfh4p, or Sfh5p rescues sec14-associated growth and secretory defects in a phospholipase D (PLD)-sensitive manner. Several independent lines of evidence further demonstrate that SFH PITPs are collectively required for efficient activation of PLD in vegetative cells. These include a collective requirement for SFH proteins in Sec14p-independent cell growth and in optimal activation of PLD in Sec14p-deficient cells. Consistent with these findings, Sfh2p colocalizes with PLD in endosomal compartments. The data indicate that SFH gene products cooperate with "bypass-Sec14p" mutations and PLD in a complex interaction through which yeast can adapt to loss of the essential function of Sec14p. These findings expand the physiological repertoire of PITP function in yeast and provide the first in vivo demonstration of a role for specific PITPs in stimulating activation of PLD.

Base Sequence↗

Reproductive toxicity of 1-bromopropane, a newly introduced alternative to ozone layer depleting solvents, in male rats.

1-Bromopropane has been newly introduced as an alternative to ozone-depleting solvents. We aimed to clarify its dose-dependent reproductive toxicity in male rats. Thirty-six Wistar male rats were randomly divided into 4 groups of 9. The groups were exposed to 200, 400, or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 12 weeks. Epididymal sperm indices were evaluated after a 12-week exposure. The testes, epididymides, seminal vesicle, prostate, and other organs were weighed and examined histopathologically. Spermatogenic cells, in stage VII seminiferous tubules, and retained spermatids, at the basal region of stages IX-XI seminiferous epithelium, were counted. Plasma testosterone levels were measured by radioimmunoassay. The testicular weight did not significantly change, but the weight of epididymides, seminal vesicle, and prostate dose-dependently decreased. The weight of seminal vesicle decreased significantly at the lowest concentration of 200-ppm and over. 1-Bromopropane induced a dose-dependent decrease in the epididymal sperm count and in motility, as well as an increase in tailless sperm and sperm with an immature head shape. The spermatogonia, preleptotene spermatocytes, pachytene spermatocytes, and round spermatids did not decrease significantly at stage VII. Retained, elongated spermatids near the basement membrane at the postspermiation stages IX-XI increased dose-dependently. Plasma testosterone levels significantly decreased at the 800-ppm dosage. 1-Bromopropane caused failure of spermiation. Its reproductive toxicity is different from that of 2-bromopropane, which specifically impairs spermatogonia. Thus, this solvent may have serious reproductive toxic effects in men, and should be used very cautiously in the workplace.

Administration, Inhalation↗

1-Bromopropane, an alternative to ozone layer depleting solvents, is dose-dependently neurotoxic to rats in long-term inhalation exposure.

1-Bromopropane has been newly introduced as an alternative to ozone layer-depleting solvents. We aimed to clarify the dose-dependent effects of 1-bromopropane on the nervous system. Forty-four Wistar male rats were randomly divided into 4 groups of 11 each. The groups were exposed to 200, 400, or 800 ppm of 1-bromopropane or only fresh air 8 h per day for 12 weeks. Grip strength of forelimbs and hind limbs, maximum motor nerve conduction velocity (MCV), and distal latency (DL) of the tail nerve were measured in 9 rats of each group every 4 weeks. The other 2 rats of each group were perfused at the end of the experiment for morphological examinations. The rats of the 800-ppm group showed poor kicking and were not able to stand still on the slope. After a 12-week exposure, forelimb grip strength decreased significantly at 800 ppm and hind limb grip strength decreased significantly at both 400 and 800 ppm or after a 12-week exposure. MCV and DL of the tail nerve deteriorated significantly at 800 ppm. Ovoid or bubble-like debris of myelin sheaths was prominent in the unraveled muscular branch of the posterior tibial nerve in the 800-ppm group. Swelling of preterminal axons in the gracile nucleus increased in a dose-dependent manner. Plasma creatine phosphokinase (CPK) decreased dose-dependently with significant changes at 400 and 800 ppm. 1-Bromopropane induced weakness in the muscle strength of rat limbs and deterioration of MCV and DL in a dose-dependent manner, with morphological changes in peripheral nerve and preterminal axon in the gracile nucleus. 1-Bromopropane may be seriously neurotoxic to humans and should thus be used carefully in the workplace.

Administration, Inhalation↗

Harpin-induced hypersensitive cell death is associated with altered mitochondrial functions in tobacco cells.

Mitochondria play important roles in animal apoptosis and are implicated in salicylic acid (SA)-induced plant resistance to viral pathogens. In a previous study, we demonstrated that SA induces rapid inhibition of mitochondrial electron transport and oxidative phosphorylation in tobacco cells. In the present study, we report that plant programmed cell death induced during pathogen elicitor-induced hypersensitive response (HR) is also associated with altered mitochondrial functions. Harpin, an HR elicitor produced by Erwinia amylovora, induced inhibition of ATP synthesis in tobacco cell cultures. Inhibition of ATP synthesis occurred almost immediately after incubation with harpin and preceded hypersensitive cell death induced by the elicitor. Diphenylene iodonium, an inhibitor of the oxidative burst, did not block harpin-induced inhibition of ATP synthesis or cell death, suggesting that oxidative burst was not the direct cause for these two harpin-induced processes. Unlike SA, harpin had no significant effect on total respiratory O2 uptake of treated cells. However, respiration of harpin-treated tobacco cells became very sensitive to the alternative oxidase inhibitors salicyl-hydroxamic acid and n-propyl gallate. Thus, harpin treatment resulted in reduced capacity of mitochondrial cytochrome pathway electron transport, which could lead to the observed inhibition of ATP synthesis. Given the recently demonstrated roles of mitochondria in apoptosis, this rapid inhibition of mitochondrial functions may play a role in harpin-induced hypersensitive cell death.

Adenosine Triphosphate↗

Metabolic regulation of Na(+)/P(i)-cotransporter-1 gene expression in H4IIE cells.

We showed that the rat Na(+)/P(i) cotransporter-1 (RNaPi-1) gene was regulated by insulin and glucose in rat hepatocytes. The aim of this work was to elucidate signaling pathways of insulin-mediated metabolic regulation of the RNaPi-1 gene in H4IIE cells. Insulin increased RNaPi-1 mRNA abundance in the presence of glucose and decreased RNaPi-1 mRNA in the absence of glucose, clearly establishing an involvement of metabolic signals for insulin-induced upregulation of the RNaPi-1 gene. Pyruvate and insulin increased RNaPi-1 expression but downregulated L-pyruvate kinase, indicating the existence of gene-specific metabolic signals. Although fructose, glycerol, and lactate could support insulin-induced upregulation of the RNaPi-1 gene, compounds entering metabolism beyond pyruvate oxidation, such as acetate and citrate, could not, suggesting that RNaPi-1-specific metabolic signals are generated at or above pyruvate oxidation. Wortmannin, LY-294002, and rapamycin abolished the insulin effect on the RNaPi-1 gene, whereas expression of dominant negative Asn(17) Ras and mitogen-activating protein kinase (MAPK) kinase (MEK) inhibitor PD-98059 exhibited no effect. Thus we herein propose that metabolic regulation of RNaPi-1 expression by insulin is mediated through the phosphatidylinositol 3-kinase/p70 ribosomal S6 kinase pathways, but not the Ras/MAPK pathway.

Adenoviridae↗

HIV gp120 enhances NO production by cardiac myocytes through p38 MAP kinase-mediated NF-kappaB activation.

Human immunodeficiency virus (HIV) infection is associated with a surprisingly high frequency of myocardial dysfunction. Potential mechanisms include direct effects of HIV, indirect effects mediated by cytokines, or a combination. We have previously reported that interleukin-1beta (IL-1beta) (500 U/ml) alone induced nitric oxide (NO) production by neonatal rat cardiac myocytes (CM). Effects of the HIV-1 envelope, glycoprotein120 (gp120), on inducible NO synthase (iNOS) in CM have not been previously reported. Unlike IL-1beta, recombinant HIV-gp120 (1 microgram/ml) alone failed to enhance NO production in CM (0.5 +/- 0.4 vs. 0.4 +/- 0.5 micromol/1.25 x 10(5) cells/48 h, gp120 vs. control, respectively; n = 12, P = not significant). However, the addition of gp120 to IL-1beta significantly enhanced iNOS mRNA expression (70 +/- 1.5 vs. 26 +/- 2.4 optical units, IL-1beta + gp120 vs. IL-1beta, respectively; n = 3), iNOS protein synthesis (42 +/- 1.4 vs. 18 +/- 0.8 optical units, IL-1beta + gp120 vs. IL-1beta, respectively; n = 3), and NO production (NO(2)(-)) (6.6 +/- 0.6 vs. 4.1 +/- 0.8 micromol/1.25 x 10(5) cells/48 h, IL-1beta + gp120 vs. IL-1beta, respectively; n = 12, P </= 0.5). HIV-gp120 enhancement of IL-1beta-induced NO(2)(-) production was blocked by 10 microM of SB-203580 (SB), a selective p38 protein kinase inhibitor (3.6 +/- 0.2 vs. 6.6 +/- 0.6 micromol/1. 25 x 10(5) cells/48 h, IL-1beta + gp120 + SB vs. IL-1beta + gp120, respectively; n = 12, P </= 0.5). HIV-gp120-enhanced p38 protein kinase activity was associated with an increase in IL-1beta-stimulated NF-kappaB activity (184 +/- 12.7 vs. 92 +/- 10.7 optical units, IL-1beta + gp120 vs. IL-1beta, respectively; n = 3). None of these effects was seen with another recombinant HIV-1 protein, Tat. Thus HIV-gp120 enhancement of IL-1beta-induced NO production is associated with p38-mediated activation of NF-kappaB. Direct effects of HIV-gp120 on CM may provide a previously unrecognized mechanism contributing to HIV cardiomyopathy.

Animals↗

Autocorrelation function analysis of ECG signals in 20 rabbits.

In this experiment, we measured ECG signals of lead I, respectively, during normal and arrhythmia after 20 rabbits were anaesthetized. These signals were recorded, then the information was put into a computer and it analyzed Autocorrelation (AC) Function, and Power Spectrum. The results make us know: (1) periodicity corresponding relationship of ECG in normal rabbits can derive reflects from changes of ECG AC function changes of ECG signals in arrhythmia rabbits can derive relatively sensitive reflection from changes of ECG function (attenuating area S and the value of k) in normal rabbits. (2) The Autocorrelation Function of Electrocardio change but ECG in the normal. All these provide another useful method for the diagnosis of arrhythmia.

Animals↗

[Element concentrations in Rheum palmatum and R. likiangense plants and soil in Tibet plateau].

The characteristics of element concentrations in Rheum palmatum and R. likiangense plants and soil were studied using ICP method. The results showed that the P concentrations in soil was significantly lower than that in leaves and rhizomes; Fe concentration was 50-100 times higher in soil than in rhizomes, and leaves, and without significant difference between rhizomes and leaves; Na, Mn and Cu concentrations appeared soil > leaves > rhizomes; and Ca concentration showed soil < leaves < rhizomes for R. palmatum, and soil > leaves > rhizomes for R. likiangense. Although K, Mg, Ca, Mn and Zn concentrations were obviously different between soils of the 2 species, K and Mg concentrations were consistent in their leaves or rhizomes, and the difference of Ca, Mn and Zn concentrations between their rhizomes was insignificant.

Calcium↗

[Radial artery for coronary artery bypass grafting: operative techniques and early results].

OBJECTIVE: To review the experience coronary artery bypass grafting (CABG) with the radial artery (RA) performed from June 1997 to December 1999. METHODS: A total of 71 patients received CABG in whom the performance of the radial and ulnar arteries were checked preoperatively with the modified Allen's test. A curvilinear skin incision was made from 3 cm distal to the cubital fossa to 2 cm before the proximal crease at the wrist. The RA was mobilized together with its satellite veins and surrounding fat tissues. Small branches were divided between titanium clips. Direct touching on the RA trunk was totally avoided and use of diathermy was minimized. A 1% papaverine solution of heparinized Ringer's was applied intraluminally into the free RA graft before it was stored in the same solution for later use. Seventy-two RAs were harvested and 79 distal anastomoses were made mostly to the posterior descending branches and the circumflex marginal branches. All the proximal anastomoses were directed to the aorta. Calcium channel blockers were routinely used for a period of 6 months postoperatively. RESULTS: There was 1 death for an operative mortality of 1.4%. The death was not caused by failure of RA graft. There was no compartment syndrome or hand ischemia. No perioperative myocardial infarction was observed. CONCLUSIONS: It is easy and safe to use the RA for CABG by which good results can be achieved. A'no-touch' harvesting technique and use of calcium-channel blockers are essential to the functioning of this conduit.

Adult↗

[The recognition of the epidemic area of tsutsugamushi disease on Nan Peng Lie Island in China and the strategy of prevention].

OBJECTIVE: To investigate the region for the epidemic area of tsutsugamushi disease. METHODS: Epidemiological studies, Orientia tsutsugamushi isolation, and preventive measures were used. RESULTS: The region belonged to epidemic area of south subtropical zone. The main host was found Rattus norvegicu. The main biological vector was Leptotrombidium deliens. The seasonal trends of the quantity of Rattus norvegicu and Leptotrombidium deliens were consistent with the incidence change of the disease in the region. Orientia tsutsugamushi has been isolated from Rattus norvegicu and Leptotrombidium deliens. Data showed that Orientia tsutsugamushi isolated strains mainly belongs to Karp. Sero-epidemiological data showed that antibodies of Orientia tsutsugamushi are 100.0% positive in the residents of the region and 4.0% in army men. After taking comprehensive preventive measures, the incidence was descending. CONCLUSION: Nan Peng Lie island was proved an epidemic area of tsutsugamushi disease.

Animals↗

[Bacillus subtilis undergoes natural genetic transformation on agar plates].

This paper conducted preliminary investigation on natural genetic transformation of Bacillus subtilis on agar plates. The results showed that, under same conditions, the natural transformation of the strain on agar plate was much more efficient than that of standard liquid method, and the transformation system could sustain higher DNase concentration. In addition, that the LB culture, which usually did not support the strain acquire competency, could undergo transformation as soon as it being spread on agar plate, suggested that the natural genetic transformation of Bacillus subtilis on solid plates may be different form the standard liquid transformation method. The cell-to-cell transformation between strains having different genetic makers could also be observed on agar plates.

Agar↗