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Biomedical subjects

Z Guan

Publications and source records attributed to Z Guan.

At least 91 records · Page 5Linked to original sources

Nitric oxide amplifies interleukin 1-induced cyclooxygenase-2 expression in rat mesangial cells.

Interleukin 1 and nitric oxide (NO) from infiltrating macrophages and activated mesangial cells may act in concert to sustain and promote glomerular damage. To evaluate if such synergy occurs, we evaluated the effect if IL-1 beta and NO on the formation of prostaglandin (PG)E2 and cyclooxygenase (COX) expression. The NO donors, sodium nitroprusside and S-nitroso-N-acetylpenicillamine, alone did not increase basal PGE2 formation. However, these compounds amplified IL-1 beta-induced PGE2 production. Similarly, sodium nitroprusside and S-nitroso-N-acetylpenicillamine by themselves did not induce mRNA and protein for COX-2, the inducible isoform of COX; however, they both potentiated IL-1 beta-induced mRNA and protein expression of COX-2. The stimulatory effect of NO is likely to be mediated by cGMP since (a) an inhibitor of the soluble guanylate cyclase, methylene blue, reversed the stimulatory effect of NO donors on COX-2 mRNA expression; (b) the membrane-permeable cGMP analogue, 8-Br-cGMP, mimicked the stimulatory effect of NO donors on COX-2-mRNA expression; and (c) atrial natriuretic peptide, which increases cellular cGMP by activating the membrane-bound guanylate cyclase, also amplified IL-1 beta-induced COX-2 mRNA expression. These data indicate a novel interaction between NO and COX pathways.

Animals↗

Broadband quadrupolar axialization of large multiply charged ions to enhance measurement and minimize conformational restrictions.

For high-resolution Fourier transform mass spectrometry of electrosprayed proteins, the signal-to-noise ratio of measuring nozzle-skimmer fragment ions can be improved substantially by their broadband quadrupolar axialization (QA), even without increasing their concentration in the ion cyclotron resonance cell. Axialization of the product ions makes possible larger, more concentric ion orbits for measurements. QA allowed the identification of new sequence-indicative product ions from a 29 kDa protein. However, QA of large molecular ions gives little increase in signal, consistent with original trapping near the cell axis. By recentering of ions undergoing ion-molecule reactions, these can be carried out at much higher kinetic energy and pressures; for cytochrome c this increases the achievable H-D exchange by 40%, corresponding to exchange at all the active sites of its completely denatured conformer.

Carbonic Anhydrases↗

Lipid composition in scrapie-infected mouse brain: prion infection increases the levels of dolichyl phosphate and ubiquinone.

The neutral and phospholipid composition of mouse brain infected with scrapie prions was investigated. During the later stages of this disease, the level of dolichol decreased by 30% whereas the level of dolichyl phosphate increased by 30%. In terminally ill mice, there was also a 2.5-fold increase in both total ubiquinone and its reduced form. Furthermore, alpha-tocopherol was elevated at this stage by 50%. In contrast, no changes were observed in phospholipid amount, in phospholipid composition, and in phosphatidylethanolamine plasmalogen content during the entire disease process. The fatty acid and aldehyde composition of individual phospholipids remained unaltered as well. No modifications could be detected in cholesterol content. Thus, the majority of membrane lipids in scrapie-infected mouse brain are modified in neither quantity nor structure, but specific changes occur to a few polyisoprenoid lipids. This specificity indicates that, although prions accumulate in lysosomes, the infection process is not associated with a general membrane destruction caused by lysosomal enzyme leakage.

Animals↗

Activation of elements of the phosphatidylinositol pathway in the primate corpus luteum by prostaglandin E2.

The current study was designed to examine the effects of prostaglandin (PG) E2 on progesterone production by primate luteal cells collected during the late luteal phase. PGE2 inhibited basal and human chorionic gonadotrophin (HCG)-stimulated progesterone production (P < 0.01) in late luteal phase corpora lutea. The ability of PGE2 to activate a second messenger system (phosphatidylinositol pathway) in corpora lutea of rhesus monkeys was also assessed. PGE2 significantly increased the accumulation of inositol phosphates (P < 0.05). This stimulation was not apparent in the early luteal phase but was manifested in the mid-late luteal phase. PGE2 also caused a rapid, yet transient, increase (P < 0.01) in intracellular free calcium ion concentrations ([Ca2+]i) in a large proportion of primate luteal cells. The proportion of luteal cells that responded to PGE2 with an increase in [Ca2+]i was smaller (P < 0.05) in corpora lutea collected during the early luteal phase (12%) in comparison with those collected during the latter half of the luteal phase (63-66%). Changes in [Ca2+]i in response to PGE2 were similar in small and large luteal cells. This study demonstrates that PGE2 activates elements of the phosphatidylinositol pathway in primate corpora lutea. This activation is augmented as the luteal phase progresses. Thus, the inhibitory effects of PGE2 on luteal progesterone production observed in the late luteal phase are associated with activation of elements of the phosphatidylinositol pathway.

Animals↗

Injury to vascular endothelial cells and the change of plasma endothelin level in dogs with gunshot wounds.

The purpose of this study was to evaluate the relationship between injury to endothelial cells and the plasma endothelin level after gunshot wounds. Forty dogs were divided into four groups. The dogs in group 1 served as a control. The dogs in groups 2,3, and 4, respectively, were shot in both hind legs, in the hypogastric part of the abdomen, or in the right chest by military bullets (5.56 mm or 7.62 mm). After wounding, blood samples were taken at different intervals and the number of circulating endothelial cells (CEC), an indicator of injury to vascular endothelial cells (VEC), and the level of plasma endothelin were measured. Results showed that the CEC number increased in all groups immediately after wounding and showed a peak value at 10 minutes and at 6 hours. The change in plasma endothelin level paralleled that of the change of CEC number, and a linear relationship was found between them. These results suggest that, in gunshot wounds, extensive injury to VEC may be the result of the temporary cavity and shock waves produced by high velocity missiles striking the body and causing secretions of endothelin. The mechanism of injury to VEC after a gunshot wound in discussed in this paper.

Animals↗

Interleukin-1 beta activates c-jun NH2-terminal kinase subgroup of mitogen-activated protein kinases in mesangial cells.

We investigated whether JNK is activated by interleukin-1 beta (IL-1 beta) in mesangial cells. We performed in-gel kinase assays with His-c-jun-(1-79), which contains the amino-terminal activation domain of c-jun and a mutant His-c-jun in which Ser-63 and Ser-73 of His-c-jun were mutated to Ala as the substrates. JNK1 (p45) and JNK2 (p54) isoforms phosphorylated His-c-jun in mesangial cells. IL-1 beta produced a time- and concentration-dependent increase in JNK activity. IL-1 beta did not phosphorylated the mutant, His-c-jun. The IL-1 beta-activated JNK activity was independent of serum and suppressed by neither tyrosine kinase inhibitors nor protein kinase C inhibitors. JNK was also stimulated by anisomycin and okadaic acid but not by phorbol 12-myristate 13-acetate. The protein synthesis inhibitors and okadaic acid potentiated the IL-1 beta-induced JNK activity. Together, these studies indicate that the novel JNK group of protein kinases may play an important role in the signal transduction pathway initiated by proinflammatory cytokines, such as IL-1 beta in mesangial cells.

Animals↗

[Clinical observation of the pathological changes of axial length, corneal curvature and posterior segment wall of eyeball in eyes with high myopia].

PURPOSE: To study the correlation between the characteristics of the morphologic changes in the wall of eyeball with high myopia and the visual function. METHODS: The axial length, corneal curvature, etc., of 280 eyes in 140 cases (the diopter was from -6.25D to approximately -30.00D) were examined and the data were settled statistically. RESULTS: (1) The corrected visual acuity in the patents with high myopia decreased apparently with the increase of diopter. The difference was significant (P < 0.001). (2) The axial length of anteroposterior diameter in 96.1% eyes increased, with which the diopter also increased. (3) 27.1% exophthalmos were forward. (4) There was no significant difference when compared the anterior surface corneal curvature with emmetropic eyes. (5) Posterior scleral staphyloma occurred in 80.7% eyes. (6) Optic nerve atrophy and optic disk atrophic arc spot occurred in 82.3% eyes. (7) The intraocular pressure increases in 5.3% eyes. CONCLUSION: The severe damage to the visual function because of the pathological changes on the wall of eyeball is the main cause that vision can not be corrected in clinics.

Adolescent↗

[The effects of retinoic acid on the ultrastructure of cultured fibroblasts].

The paper reports the effects of retinoic acid on the ultrastructure of cultured fibroblasts. Electron microscopic observation (SEM and TEM) showed that fibrous substances on the cell surface and outside the cell had decreased. The results indicated that retinoic acid inhibits collagen synthesis of fibroblasts. The possible mechanism of the effect of retinoic acid in the treatment of scar is discussed.

Collagen↗

Effect of tumor necrosis factor alpha on rabbit corneal endothelial permeability.

PURPOSE: Tumor necrosis factor alpha (TNF alpha) is present in the iris and the lacrimal gland, and its concentration is increased during inflammation and after corneal wounding. Although TNF alpha has been shown to increase keratocyte and corneal epithelial interleukin production, no definitive effects of TNF alpha on corneal endothelial cells have been reported. TNF alpha has been shown to disrupt barrier function in vascular endothelial monolayers through f-actin depolymerization. A reduction in intracellular cyclic adenosine monophosphate (cAMP) concentration may play a role in this response. This study was designed to examine the role and signal transduction mechanisms of TNF alpha modulation of endothelial permeability in the cornea. In addition, it is the first examination of the effects of TNF alpha on the barrier function of a noncultured cell monolayer. METHODS: Rabbit corneal endothelial superfusions were performed under an in vitro specular microscope. Corneas were processed for permeability measurements or f-actin staining. RESULTS: TNF alpha superfused corneas had significantly higher permeabilities than controls. f-actin staining revealed that TNF alpha superfusion disrupted f-actin filaments when compared to controls. Corneas superfused with the f-actin stabilizing agent phallacidin had significantly lower permeabilities than TNF alpha superfused pairs. Permeabilities of corneas superfused with TNF alpha plus 8-bromo-cAMP (0.01 to 3 mM) were significantly lower than TNF alpha superfused pairs at all concentrations, although only significantly lower at the 0.1 mM cAMP concentration. CONCLUSIONS: TNF alpha causes an increase in corneal endothelial permeability, and this increase is mediated by disruption of f-actin filaments; cAMP appears to be involved in this response.

8-Bromo Cyclic Adenosine Monophosphate↗

[Effect of dexamethasone on the human interleukin-2 receptor alpha chain gene expression].

Glucocorticoids have wide effects on the immune system, the mechanisms of these effects have not been clearly defined. The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) is a critical control point in the T-cell mediated immune response. The effect of dexamethasone, a synthetic glucocorticoid hormone, on IL-2R is unclear in comparison with its inhibition on the accumulation of IL-2 mRNA. Our study shows that dexamethasone increases the basal and PHA-induced mRNA levels of IL-2R alpha gene in Jurkat cells, but it does not affect the expression of reporter gene constructs containing 5' flanking sequences (-482bp/ +16bp or -350bp/+16bp) of the IL-2R alpha gene in PHA activated Jurkat cells. These results indicate that dexamethasone plays a positive regulatory role in the IL-2R alpha gene expression, but the effect is not mediated by the previously identified proximal regulatory elements located between -482bp/+1bp. Meanwhile, our results also provide evidence that the activation mechanism of dexamethasone is different from that of PHA, and that dexamethasone and PHA show a synergistic effect in the induction of IL-2R alpha gene expression.

Cell Line↗

[The microscopic vasculitis in tongue].

This is the first report of 16 cases with microscopic vasculitis of the tongue in Chinese literatures. The clinical manifestations and histopathology of the disease were described. The treatment of promoting blood circulation to remove blood was used stasis. Probably the microscopic vasculitis plays an importment role in the glossodynia.

Aged↗

[Significance of the expression of HLA-DR on keratinocytes in oral lichen planus lesions].

In this article, the expression of HLA-DR in keratinocytes in lesions of oral lichen planus (OLP) was investigated, using an immunohistochemical technique (PAP method). The results showed: HLA-DR positive keratinocytes were found in all groups of patients, the numbers and expressive degree of HLA-DR were related to types and duration of OLP, there were higher statistically significant differences between different groups and types of OLP (P < 0.01). The authors considered that the expression of HLA-DR in keratinocytes plays an important role in gathering T cells and forming inflammation in OLP lesions.

Adult↗

Real-time monitoring of the gas phase reactions of a single ion population using the remeasurement experiment in Fourier transform ion cyclotron resonance mass spectrometry.

A single population of multiply charged protein ions formed by electrospray ionization is held in a trapped ion cell and remeasured continuously by Fourier transform ion cyclotron resonance (FTICR) mass spectrometry while undergoing multiple reactions with diethylamine. In a first example, electrosprayed horse myoglobin with an average of 16 attached protons is reacted with base at a pressure of 1.5 x 10(-8) Torr for a period of 60 s. A total of 31 spectra acquired with a duty cycle of 2 s exhibit the charge state-dependent formation of up to three diethylamine adducts and removal of up to nine protons. A realtime measuring experiment is then conducted over a 1 h period to observe charge stripping of electrosprayed myoglobin ions, leaving as few as seven charges. Realtime monitoring is used to evaluate the effect of reagent gas pressure on adduct formation and is used in conjunction with high mass resolution FTICR detection to resolve the isotopic peaks within individual charge states of adduct spectra. The attractive features of real-time reaction monitoring include a dramatic reduction in experiment time and sample consumed while concurrently observing long-lived intermediates and reaction products as they form.

Cyclotrons↗

Staurosporine affects calcium homeostasis in cultured bovine adrenal chromaffin cells.

These studies show that the potent, non-specific, protein kinase inhibitor, staurosporine, disrupts Ca2+ homeostasis in cultured bovine adrenal chromaffin cells. Staurosporine treatment reduces basal and A23187-stimulated catecholamine release from chromaffin cells, but does not inhibit activated Ca2+ influx. Furthermore, pretreatment with staurosporine also reduces Ca(2+)-stimulated catecholamine release from digitonin-permeabilized cells (t1/2, 40.6 min; IC50, 66.0 nm). However, staurosporine does not inhibit the rise in intracellular Ca2+ ([Ca2+]i) in response to nicotine stimulation as measured by fura-2 photometry. These studies demonstrate that staurosporine interferes with the secretory process at some step at or after the rise in [Ca2+]i in adrenal chromaffin cells. Examination of the effects of staurosporine on 45Ca2+ movement shows that staurosporine produces a slowly developing basal 45Ca2+ accumulation; after 30 min no significant change is observed, but by 120 min, 45Ca2+ accumulation is increased by 29.5%. Thapsigargin and 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBHQ), inhibitors of Ca(2+) ATPases, were used to determine whether staurosporine induced 45Ca2+ accumulation results from sequestration of 45Ca2+ within intracellular stores. While thapsigargin has no significant effect, concomitant treatment with tBHQ prevents the increase in 45Ca2+ uptake associated with staurosporine treatment. Therefore, the tBHQ-sensitive Ca2+ store, but not the thapsigargin/inositol 1,4,5-triphosphate-sensitive Ca2+ store, appears to be staurosporine-sensitive. Overall, these studies indicate that staurosporine reduces catecholamine release by interfering with Ca2+ homeostasis. Furthermore, this work suggests that a staurosporine-sensitive phosphoprotein(s) is involved with the regulation of Ca2+ homeostasis in bovine adrenal chromaffin cells.

Alkaloids↗

Cell geometry considerations for the Fourier transform ion cyclotron resonance mass spectrometry remeasurement experiment.

Three cell geometries, closed cubic, closed elongated, and open elongated, are evaluated for optimum remeasurement performance in the Fourier transform ion cyclotron resonance mass spectrometry (FTICR) experiment. The advantages and disadvantages of each cell during normal FTICR operation are discussed. Unit remeasurement efficiency is obtained for the closed elongated cell at approximately 71% of the cell radius, whereas the open elongated cell achieves unit remeasurement at only approximately 18% of the cell radius. The closed cubic cell does not achieve unit remeasurement efficiency at a detectable signal level. A correlation between remeasurement efficiency and the characteristic radial electric field of each trapped ion cell is established. Radial dispersion of the ion cloud is considered the dominant signal loss mechanism in the remeasurement experiment, and cell geometries are examined for optimized sensitivity and unit remeasurement efficiency.

Electricity↗

Gangliosides inhibit PDGF-induced signal transduction events in U-1242 MG human glioma cells.

In this study we investigated the responses of intracellular calcium ([Ca2+]i) and protein kinase C (PKC) to PDGF in U-1242 MG cells. PDGF-BB stimulated [3H]PDBu binding approximately 2-3 fold. This response was inhibited by preincubating the cells with an inhibitor of phospholipase C (PLC), U73122, suggesting that PLC mediates the induction of PKC translocation by PDGF. PDGF also increased the concentration of [Ca2+]i that was attenuated in a calcium-free medium. This indicates that PDGF-induced elevation of [Ca2+]i is mainly due to influx of extracellular calcium. PDGF-stimulated translocation of PKC was inhibited by the intracellular calcium buffer BAPTA/AM. All gangliosides studied except GM3 inhibited these responses with similar efficacy. Collectively, these results indicate that the signal transduction pathway initiated by PDGF leading to PKC translocation in U-1242 MG cells is intact, and this pathway is inhibited by several gangliosides.

Calcium↗

Arachidonic acid inhibits hCG-stimulated progesterone production by corpora lutea of primates: potential mechanism of action.

Arachidonic acid (AA) is a precursor of metabolites known to affect the corpus luteum (CL) in many species, including primates. We have shown that some of these products (prostaglandins F2 alpha and E2) inhibit pro-gesterone (P4) production and activate the phosphatidylinositol (PI) pathway in CL of rhesus monkeys. A direct role of AA in luteal function has also been suggested. The current experiments were designed to investigate the effect of AA on P4 synthesis and to examine the ability of AA to activate the PI pathway in CL of rhesus monkeys. Basal and hCG-stimulated P4 production by luteal cells collected during the midluteal phase was measured after treatment with AA (1, 5, and 10 microM) or linoleic acid (1, 5, and 10 microM). Dispersed cells (50,000/tube) were incubated at 37 degrees C for 2 h. AA elicited a dose-dependent decrease in hCG-stimulated, but not in basal, P4 production. hCG-stimulated P4 production was reduced (P < 0.01) at AA doses of 5 microM (12.1 +/- 1.5 ng/mL) and 10 microM (8.6 +/- 1.8 mg/mL) to hCG alone (18 +/- 1.6 ng/mL). There was no significant effect of 1 microM AA (15.2 +/- 1.6). Response to linoleic acid was dissimilar and was not dose-dependent. Viability of cells was not affected by any treatment. Indomethacin, a prostaglandin synthesis inhibitor, and nordihydroguaiaretic acid, an inhibitor of lipoxygenase, did not interfere with the inhibitory effect of AA. Activation of the PI pathway was assessed by monitoring the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to inositol phosphates and by monitoring increases in intracellular free calcium concentrations ([Ca2+]i) in individual cells. Moreover, the ability of AA to activate protein kinase C (PKC) in luteal cells was measured using a [3H]phorbol dibutyrate (PDBu) binding assay. AA did not alter PIP2 hydrolysis or [Ca2+]i, however, AA (10 microM) increased specific binding of [3H]PDBu to luteal cells (P < 0.05). We conclude that AA inhibits hCG-stimulated P4 production by primate luteal cells. AA exerts this action without being converted to prostaglandins or leukotrienes. This inhibition may be mediated through the activation of PKC. These results suggest a possible role for AA in the regulation of luteal function in primates, and that PKC-activation by AA may promote its effects.

Animals↗