Search PubMed⌕ Search

Biomedical subjects

X Guo

Publications and source records attributed to X Guo.

At least 397 records · Page 22Linked to original sources
PubMed1995

Stimulation of Cl- secretion by extracellular ATP does not depend on increased cytosolic Ca2+ in HT-29.cl16E.

Extracellular ATP and elevated cytosolic Ca2+ concentration ([Ca2+]i) are major secretagogues for Cl- in the goblet cell-like clone cl.16E derived from colonic HT-29 cells. The involvement of [Ca2+]i as a messenger for the purinergically stimulated Cl- secretion was investigated using whole cell patch-clamp and Ussing chamber techniques, as well as [Ca2+]i measurements using fura 2-loaded cells. Under voltage-clamp conditions, the whole cell current at +50 mV was 3 +/- 1 pA/pF under unstimulated conditions. Stimulation of purinergic receptors with 200 microM extracellular ATP increased the current at +50 mV to 41 +/- 10 pA/pF, with a half-maximal effective dose (ED50) of approximately 3 microM. The current was transient, usually lasting 1-2 min, and the current-voltage relationship was approximately linear between -70 and +50 mV. Evidence that the ATP-stimulated current was carried by Cl- included 1) the reversal potential of the current closely followed the Cl- equilibrium potential, and 2) the stimulated current was absent when Cl- was removed from both bath and pipette solutions. Exposure to ATP also increased [Ca2+]i, with an ED50 of approximately 1 microM and maximal changes (at 200 microM) from baseline (71 +/- 3 nM) to 459 +/- 50 nM. The ATP-dependent Cl- conductance increase was not diminished when [Ca2+]i was clamped at 100 nM using a Ca(2+)-1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid or Ca(2+)-ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid buffering system. However, the ATP effect did require some basal level of Ca2+ because clamping [Ca2+]i at < 10 nM abolished activation of the Cl- conductance. The presence of the protein kinase A inhibitor H-89 or the protein kinase C inhibitor staurosprine did not change the ATP-activated Cl-conductance. These data demonstrate that the ATP-stimulated increase in Cl- current does not require an increase in [Ca2+]i, suggesting the involvement of either another signaling pathway or direct activation of Cl- channels by purinergic receptors.

Adenosine Triphosphate↗
PubMed1995

Hemocyte alterations during melanotic encapsulation of Brugia malayi in the mosquito Armigeres subalbatus.

The involvement of hemocytes in melanotic encapsulation reactions against Brugia malayi was assessed in Armigeres subalbatus. Hemocyte populations, epitope changes, phenol oxidase (PO) activity, and the presence of an 84-kDa polypeptide were investigated in mosquitoes exposed to a B. malayi-infective bloodmeal (= immune-activated), in mosquitoes given a noninfective bloodmeal (= controls), in nonbloodfed mosquitoes (= naive), or in some combination of these. Total hemocyte populations in immune-activated mosquitoes significantly decreased at 24 hr postbloodmeal (PB) as compared with controls. At 48 and 72 hr PB, hemocyte population levels in immune-activated mosquitoes increased to control levels. Epitope changes, as indicated by wheat germ agglutinin (WGA) binding, also were observed. There was a significant increase in the percentage of hemocytes binding WGA in immune-activated mosquitoes at 24 hr PB as compared with controls. Furthermore, the activity of hemocyte PO, an enzyme involved in the melanotic encapsulation pathway, was significantly elevated at 12 hr PB in immune-activated mosquitoes as compared with controls. Analysis for the presence of an 84-kDa polypeptide in A. subalbatus indicates that a 2.0-kb message in total RNA hybridized to D6.12, an Aedes aegypti cDNA encoding an 84-kDa polypeptide that is associated with melanotic encapsulation responses. The hybridization of D6.12 to RNA was not greater in immune-activated as compared to control A. subalbatus, as has been observed in A. aegypti. Results indicate that these hemocyte changes correspond in time with the melanotic encapsulation reactions of A. subalbatus against filarial worms.

Animals↗
PubMed1995

A case-control study of the etiology of laryngeal cancer in Liaoning Province.

A case-control study of laryngeal cancer was conducted in Liaoning Province between January 1991 and April 1992 among 100 subjects with newly diagnosed cancer and 100 controls. The results of one factor analysis, odd ratio (OR), and conditional logistic regression indicated that smoking was the first significant risk factor for laryngeal cancer with an OR value of 16.8. Tobacco smoking ranked the first with an OR value of 30.4. Other factors such as alcoholic indulgence, insufficient intake of vegetable and fruits in winter and spring, air pollution in room and working environment, and fatigue of vocal cords were closely associated with the occurrence of laryngeal cancer.

Carcinoma, Squamous Cell↗
PubMed1995

Effect of hepatocytes from normal or endotoxin treated animals on the production of tumour necrosis factor, interleukin-6, and prostaglandin-E2 by macrophages incubated in vitro with various fatty acids.

OBJECTIVE: To find out if the in vitro production of tumour necrosis factor (TNF), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) by macrophages (P3888D1) were influenced by the addition to the culture media of hepatocytes from normal guinea pigs and from guinea pigs after infusion with endotoxin with and without fatty acids. DESIGN: Laboratory experiment. SETTING: University hospital, United States MATERIAL: 12 male Hartley guinea pigs. MAIN OUTCOME MEASURES: Concentrations of TNF-alpha, IL-6, and PGE2. RESULTS: Hepatocytes inhibited the production of TNF by macrophages. Those from animals pretreated with endotoxin caused a large increase in the production of PGE2 and affected the production of IL-6 only in the presence of fatty acids. Fatty acids differed from each other in their effects on production of TNF-alpha and PGE2, but had no effect on the production of IL-6. CONCLUSION: These results support the concept that hepatocytes and macrophages may interact in vivo, and this interaction may be influenced both by fatty acids that arise from lipid metabolism and from endotoxin present during sepsis and translocation.

Animals↗
PubMed1995

[Sutureless incision for intraocular lens implantation].

The technique of incisional construction, the degree of automatic closure and the results of postoperative induced corneal astigmatism were reported in a series of 50 eyes with 5.5 mm sutureless incision for 6.0 mm PMMA intraocular lens (IOL) implantation. The patients ages ranged from 8 to 72 years. In this study, I-stage implantation was performed on 13 eyes and II-stage implantation, on 37 eyes. In this group, 19 aphakic eyes had had the histories of penetrating injuries and 1 to 3 times of operations. 15 aphakic eyes had had histories of senile cataract extractions, 14 eyes were congenital cataracts and another 2 eyes were other kinds. The surgical maneuvers included an external scleral frown incision 5 mm in chord length, a scleral-tunnel dissection and a corneal internal valve incision into the corneal limbus for 1 mm and keeping horizontally 6.0 mm in width. All the implantations were smooth, incisions closed watertightly without leakage or shallow anterior chamber. The means value of induced corneal astigmatism was -0.16(0.71)D with a range of +1.00 to -1.50 D. The complications were less than that of sutured operations. The results suggest that sutureless incision be safe, reliable, self-closed tightly, less induced astigmatism and could be a better kind of incision for standard IOL implantation.

Adolescent↗
PubMed1995

[The relationship between diabetic retinopathy and cataract extraction with intraocular lens implantation in diabetics].

47 diabetics (71 eyes) having undergone cataract extraction with intraocular lens (IOL) implantation were examined and followed up. The results show that there is significant difference in the last post-operative visual acuities between the diabetic group and non-diabetic group (P < 0.01). The main cause affecting the post-operative visual acuities of the diabetics is diabetic proliferative retinopathy (P < 0.001). There is no significant difference in the post-operative visual acuities between diabetic group with or without simple diabetic retinopathy and non-diabetic group (P > 0.05). The intra- and post-operative complications in the diabetic and non-diabetic group were also investigated and there was no significant difference. IOL implantation should be guarded for diabetics with proliferative retinopathy especially when complicated with maculopathy.

Aged↗
PubMed1994

NMR studies delineating spatial relationships within the cardiac troponin I-troponin C complex.

NMR spectroscopy and selective isotope labeling of both recombinant cardiac troponin C (cTnC3) and a truncated cardiac troponin I (cTnI/NH2) lacking the N-terminal 32-amino acid cardiac-specific sequence have been used to probe protein-protein interactions central to muscle contraction. Using [methyl-13C]Met-labeled cTnC3, all 10 cTnC Met residues of Ca(2+)-saturated cTnC3 could be resolved in the two-dimensional heteronuclear single- and multiple-quantum coherence spectrum of the cTnI.cTnC complex. Based on the known Met assignments in cTnC3, the largest chemical shift changes were observed for Met81, Met120, Met137, and Met157. Methionines 120, 137, and 157 are all located in the C-terminal domain of cTnC. Methionine 81 is located at the N terminus of the central helix. Minimal chemical shift changes were observed for Met45, Met47, and Met103 of cTnC3 in the cTnI.cTnC complex. All 6 Met residues in [methyl13C]Met-labeled cTnI/NH2 could be resolved in the cTnI.cTnC complex, suggesting that both cTnI and cTnC form a stable homogeneous binary complex under the conditions of the NMR experiment. In the absence of added protease inhibitors in the cTnI.cTnC complex, cTnI/NH2 was found to undergo selective proteolysis to yield a 5.5-kDa N-terminal fragment corresponding to residues 33-80. Judging from the NMR spectra of [methyl13C]Met-labeled cTnC3, cTnI-(33-80) was sufficient for interaction with the C-terminal domain of cTnC in a manner identical to that observed for native cTnI/NH2. However, in the presence of the proteolytic fragment cTnI-(33-80), the chemical shift of Met81 was not perturbed from its position in free cTnC3. Thus, residues located C-terminal to Arg80 in cTnI appear to be responsible for interaction with the N-terminal half of cTnC. Taken together, these results provide strong evidence for an antiparallel arrangement for the two proteins in the troponin complex such that the N-terminal portion of cTnI interacts with the C-terminal domain of cTnC. This interaction likely plays a role in maintaining the stability of the TnI.TnC complex.

Animals↗
PubMed1994

Mutagenesis of cardiac troponin I. Role of the unique NH2-terminal peptide in myofilament activation.

Phosphorylation of Ser residues in the NH2-terminal extension unique to cardiac troponin I (cTnI) is known to occur through protein kinase A and to alter myofilament Ca2+ activation (Robertson, S. P., Johnson, J. D., Holroyde, M. J., Kranias, E. G., Potter, J. D., and Solaro, R. J. (1982) J. Biol. Chem. 257, 260-263). Yet, how the NH2-terminal extension may itself affect thin filament Ca2+ signaling is unknown. To approach this question we have used molecular cloning, mutagenesis, and bacterial synthesis of a full-length cTnI and a truncated mutant (cTnI/NH2) missing the 32 amino acids. Using reconstituted preparations we could show no differences between cTnI and cTnI/NH2 either in inhibition of actomyosin ATPase activity, in Ca(2+)-reversible inhibitory activity, or in the relation between pCa and Ca2+ binding to the regulatory site of cTnC at either pH 7.0 or 6.5. There were also no significant differences at either pH in the pCa-MgATPase activity relation of myofibrils into which the various species of TnI has been exchanged. Our results indicate: 1) that phosphorylation most likely induces a new state of TnI activity rather than altering an intrinsic effect of the NH2-terminal peptide on Ca2+ activation; and 2) that domains outside the NH2-terminal extension are important with regard to differences in effects of acidic pH on Ca2+ activation on cardiac and skeletal myofilaments.

Actin Cytoskeleton↗
PubMed1994

Differential secretion of catecholamines in response to peptidergic and cholinergic transmitters in rat adrenals.

1. Rat adrenal medulla is stimulated by cholinergic and peptidergic transmitters released from splanchnic nerves. The peptidergic transmitter has been identified as vasoactive intestinal polypeptide (VIP) and its contribution in comparison to that of acetylcholine (ACh) is more prominent at low neuronal activity. The purpose of this study is to determine if ACh and VIP cause differential secretion of adrenaline and noradrenaline and whether the differential secretion also occurs when splanchnic nerves are stimulated at different frequencies. 2. Perfusion of the left adrenal gland with Krebs solution for several hours did not change adrenaline and noradrenaline contents (15.2 micrograms and 3.5 micrograms, respectively) and their ratio (4.4) from those of the unperfused right adrenal medulla (15.2 micrograms, 3.3 micrograms and 4.8, respectively). 3. Perfusion with ACh (10 microM for 4 min) resulted in the secretion of 109 ng of catecholamines and the ratio of adrenaline to noradrenaline was 3.8. Although the secretion increased with increased concentrations of ACh (30 and 100 microM), the ratios remained between 3 and 4. 4. Perfusion with VIP (10 microM for 4 min) resulted in the secretion of 27 ng of catecholamines and the ratio of adrenaline to noradrenaline was 9.7. A higher concentration of VIP (20 microM for 4 min) resulted in the secretion of greater amounts of catecholamines (102 ng) without significantly altering the ratio of adrenaline to noradrenaline (10.9). 5. Perfusion with as low as 0.01 microM pituitary adenylate cyclase-activating polypeptide (PACAP) increased the secretion of catecholamines to 31 ng and the secretion increased in a dose-dependent manner up to 0.3 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Antitumor agents. 148. Synthesis and biological evaluation of novel 4 beta-amino derivatives of etoposide with better pharmacological profiles.

A series of novel 4 beta-amino derivatives of etoposide (1), which can form water-soluble salts and demonstrate excellent activity against mdr- and topo II-resistant cell lines, have been synthesized. Compared with etoposide, compounds 5-6, 8, and 10-16 show comparable or greater inhibition of human DNA topo II. In a cellular protein-DNA complex formation assay, compounds 5-6, 8, 10-14, and 16 are more potent than 1. A dose-response study of 8 shows that it is 20 times more active in formation of protein-linked DNA breaks than etoposide. Furthermore, both 8 and its free base 7 were found to be highly active toward etoposide-resistant KB cell lines. All compounds were also evaluated in vitro against a total of 56 human tumor cell lines derived from seven cancer types. Comparison of the log10 GI50 mean graph midpoints of 5-19 (-4.89 to -7.30) with that of 1 (-4.08) shows these new analogs to be 6-1659-fold more active than 1.

Antineoplastic Agents↗
PubMed1994

Antitumor agents. 144. New gamma-lactone ring-modified arylamino etoposide analogs as inhibitors of human DNA topoisomerase II.

The trans-fused gamma-lactone ring of etoposide is readily epimerized to its cis epimer, which is biologically inactive, or is metabolized to the inactive ring-opened hydroxy acids. Modification of this gamma-lactone ring of 4 beta-(arylamino)-4'-O-demethyl-4-desoxypodophyllotoxin resulted in several compounds (15-16, 21-22, and 24) that should block this epimerization and the resulting biological deactivation. In a topoisomerase II inhibition assay, compounds 21, 22, and 24 showed comparable activity to etoposide. In a protein-linked DNA complex formation assay, compounds 21 and 22 were more active than etoposide.

Antineoplastic Agents↗
PubMed1994

ATP-stimulated electrolyte and mucin secretion in the human intestinal goblet cell line HT29-Cl.16E.

The response of confluent monolayers of HT29-Cl.16E cells to stimulation by extracellular ATP and ATP analogues was investigated in terms of mucin and electrolyte secretion. Mucin secretion was measured as release of glucosamine-labeled macromolecules trapped at the stacking/running gel interface of polyacrylamide gels and electrolyte secretion as short-circuit current (Isc). Luminal ATP stimulated a transient increase in the release of mucins and of Isc corresponding to a secretory Cl- current. Both secretions peaked at 3 to 5 min after addition of ATP. Maximal ATP-stimulated mucin secretion over 15 min was up to 18-fold above control with an apparent ED50 of approximately 40 microM. Maximal peak Isc after stimulation with ATP was approximately 35 microA/cm2 with an apparent ED50 of about 0.4 mM. ATP-dependent Isc was at least in part due to Cl- secretion since removal of Cl- from the medium reduced the peak Isc by 40% and the Isc integrated over 40 min by 80%. The secretory responses were not associated with cell damage as assessed by failure of ethidium bromide to enter into the cells, absence of release of lactate dehydrogenase, maintenance of monolayer conductance, viability, and responses to repeated applications of ATP. The order of efficacy of nucleotide agonists was similar for both processes with ATP > ADP > AMP > or = adenosine. Luminal ATP was much more effective than basolateral addition of this compound. These results suggest involvement of a luminal P2-type receptor which can initiate signaling pathways for granule fusion and mucin release as well as for activation of Cl- channels. P2-receptor-stimulated mucin and Isc release was strongly inhibited by a 30 min preincubation with the classical K+ channel blockers quinine (1 mM), quinidine (1 mM), and Ba2+ (3 mM). Experiments with amphotericin B to measure separately the conductance changes of either luminal or basolateral plasma membrane revealed that quinidine did not directly block the ATP-induced basolateral K+ or the luminal anion channels. The quinidine inhibition after preincubation is therefore most easily explained by interference with granule fusion and location of anion channels in granule membranes. Luminal P2 receptors may play a role in intestinal defense mechanisms with both fluid and mucin secretion aiding in the removal of noxious agents from the mucosal surface.

Adenosine↗
PubMed1994

Production of tumor necrosis factor, interleukin-6 and prostaglandin E2 by LPS-stimulated rat bone marrow macrophages after thermal injury: effect of indomethacin.

The effect of thermal injury on the in vitro production of TNF, IL-6, and PGE2 by bone marrow-derived, LPS-stimulated rat macrophages was studied. Thermal injury caused a general hyperactivity in the production of the mediators by the cells. Indomethacin, a cyclooxygenase inhibitor of PGE2 synthesis, inhibited the production of IL-6 and PGE2 but had no effect on the production of TNF. These results suggest that the observed low concentration of PGE2 produced by the cells was insufficient to cause inhibition of TNF synthesis; thus, the effect of indomethacin would be undetectable. The results also suggest that indomethacin may act directly in inhibiting the production of IL-6 by the macrophages. The hyperactive effect of thermal injury on the production of inflammatory mediators by newly differentiated bone marrow derived macrophages can be important in the overall systemic response to the insult.

Animals↗