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Biomedical subjects

X Ji

Publications and source records attributed to X Ji.

At least 145 records · Page 8Linked to original sources
PubMed1995

[An analysis of causes of post-operative shallow anterior chamber in glaucoma filtering surgery].

131 eyes of 103 cases having undertaken glaucoma filtering surgeries were randomly selected to analyze retrospectively the causes of the post-operative shallow anterior chamber. The causes are choroidal detachment accounting for 75.6%, excessive filtration 13.3% and malignant glaucoma 11.1%. As the rate of discovery of the choroidal detachment under a direct ophthalmoscope was quite low, the definite diagnosis depended primarily on B-ultrasonography. It is discovered that in the analysis of the possible factors leading to choroidal detachment, the plasma level of fibronectin is correlated to the development of the post-operative choroidal detachment of a glaucoma filtering operation, suggesting the impairment of microcirculatory function be investigated to approach the causes of the choroidal detachment following anti-glaucoma and other intraocular surgeries.

Adult↗
PubMed1995

Functional coupling of the beta 2-adrenoceptor to a pertussis toxin-sensitive G protein in cardiac myocytes.

Recently we demonstrated that the effects of beta 2-adrenoceptor (AR) stimulation to augment Ca2+ current (ICa), cytosolic Ca2+ (Cai) transients, and contractility in rat ventricular myocytes are largely dissociated from its effect to increase cellular cAMP levels. This result suggested that beta 2ARs might be coupled to signaling pathways other than the Gs alpha-mediated activation of adenylyl cyclase. Here we show that pertussis toxin (PTX) pretreatment specifically potentiates the responses of rat heart cells to beta 2AR but not beta 1AR stimulation. After PTX pretreatment, 1) the dose-response curve for the effects of the beta 2AR agonist zinterol on contraction amplitude is shifted leftward and upward (EC50 changed from about 1.0 microM to 70 nM), 2) in indo-1-loaded cells, the maximal effects of zinterol (10(-5) M) on Cai transient and contraction amplitudes are additionally increased 1.7- and 2.0-fold, respectively, over those in control cells, and 3) the increase in ICa amplitude induced by the same zinterol concentration is potentiated by 2.5-fold. Similar effects of PTX are observed when beta 2ARs are stimulated by isoproterenol in the presence of a selective beta 1AR blocker, CGP 20712A. All effects of beta 2AR agonists in both PTX-treated and control cells are abolished by a selective beta 2AR blocker, ICI 118,551. In contrast, neither the base-line ICa, Cai transient, and contraction in the absence of beta AR stimulation nor the beta 1AR-mediated augmentations of these parameters are significantly altered by PTX treatment. These results demonstrate, for the first time, that the Gs-coupled beta 2AR can simultaneously activate a pathway that leads to functional inhibition in cardiac cells via a PTX-sensitive G protein. The activation of more than one G protein during beta 2AR stimulation, leading to functionally opposite effects, may provide a mechanism to protect the heart from Ca2+ overload and arrhythmias during the response to stress.

Adenylate Cyclase Toxin↗
PubMed1995

Study of cellulose acetate membrane-based glucose biosensors.

A new immobilization procedure was designed to covalently immobilize enzymes onto a cellulose acetate membrane that was simple and easy to handle. The resultant enzyme membrane was very stable, with high specific activity. A glucose oxidase membrane was prepared by using this method, which was combined either with an oxygen electrode or with a hydrogen peroxide electrode to construct a glucose biosensor. The response characteristics of both biosensors were compared.

Biosensing Techniques↗
PubMed1994

Incorporation of bisphosphonates into adenine nucleotides by amoebae of the cellular slime mould Dictyostelium discoideum.

Bisphosphonates are a class of synthetic pyrophosphate analogues. Some are known to be potent inhibitors of osteoclast-mediated bone resorption in vivo, but their mechanisms of action are unclear. The order of potency of bisphosphonates as inhibitors of bone resorption closely matches the order of potency as inhibitors of growth of amoebae of the slime mould Dictyostelium discoideum, indicating that bisphosphonates may have a mechanism of action that is similar in both osteoclasts and Dictyostelium. Methylenebisphosphonate and several halogenated derivatives, which have low potency as antiresorptive agents and as growth inhibitors of Dictyostelium, are metabolized intracellularly by Dictyostelium amoebae into methylene-containing adenine nucleotides. We have used a combination of n.m.r. and f.p.l.c. analysis to determine whether incorporation into nucleotides is a feature of other bisphosphonates, especially those that are potent antiresorptive agents. Only bisphosphonates with short side chains or of low potency are incorporated into adenine nucleotides, whereas those with long side chains or of high potency are not metabolized. Bisphosphonate metabolism in cell-free extracts of Dictyostelium was accompanied by inhibition of aminoacylation of tRNA by several aminoacyl-tRNA synthetases. These enzymes were barely affected by the bisphosphonates that were not metabolized. The results indicate that some bisphosphonates are not metabolically inert analogues of pyrophosphate and appear to be metabolized by aminoacyl-tRNA synthetases. The cellular effects of some bisphosphonates may be the result of their incorporation into adenine nucleotides or inhibition of aminoacyl-tRNA synthetases, although the potent bisphosphonates appear to act by a different mechanism.

Adenine Nucleotides↗
PubMed1994

Structure and function of the xenobiotic substrate binding site of a glutathione S-transferase as revealed by X-ray crystallographic analysis of product complexes with the diastereomers of 9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene.

The three-dimensional structures of isoenzyme 3-3 of glutathione (GSH) transferase complexed with (9R,10R)- and (9S,10S)-9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene [(9R,10R)-2 and (9S,10S)-2], which are the products of the addition of GSH to phenanthrene 9,10-oxide, have been determined at resolutions of 1.9 and 1.8 A, respectively. The structures indicate that the xenobiotic substrate binding site is a hydrophobic cavity defined by the side chains of Y6, W7, V9, and L12 from domain I (the GSH binding domain) and I111, Y115, F208, and S209 in domain II of the protein. All of these residues are located in variable-sequence regions of the primary structure of class mu isoenzymes. Three of the eight residues (V9, I111, and S209) of isoenzyme 3-3 that are in direct van der Waals contact with the dihydrophenanthrenyl portion of the products are mutated (V9I, I111A, and S209A) in the related isoenzyme 4-4. These three residues are implicated in control of the stereoselectivity of the class mu isoenzymes. The hydroxyl group of Y115 is found to be hydrogen-bonded to the 10-hydroxyl group of (9S,10S)-2, a fact suggesting that this residue could act as an electrophile to stabilize the transition state for the addition of GSH to epoxides. The Y115F mutant isoenzyme 3-3 is about 100-fold less efficient than the native enzyme in catalyzing the addition of GSH to phenanthrene 9,10-oxide and about 50-fold less efficient in the Michael addition of GSH to 4-phenyl-3-buten-2-one. The side chain of Y115 is positioned so as to act as a general-acid catalytic group for two types of reactions that would benefit from electrophilic assistance. The results are consistent with the notion that domain II, which harbors most of the variability in primary structure, plays a crucial role in defining the substrate specificity of class mu isoenzymes.

Animals↗
PubMed1994

Inhibitory effects of bisphosphonates on growth of amoebae of the cellular slime mold Dictyostelium discoideum.

Bisphosphonates are inhibitors of bone resorption and are used increasingly as therapeutic agents for treating clinical disorders of skeletal metabolism. Their mode of action is still not fully understood. The demonstration that methylenebisphosphonate, a simple methylene analog of pyrophosphate, inhibits the axenic growth of amoebae of the slime mold Dictyostelium discoideum and is incorporated into adenine nucleotides suggested that this organism might be useful in elucidating the cellular effects of bisphosphonates. We examined 24 bisphosphonates, including all those of clinical interest as inhibitors of osteoclast-mediated bone resorption in vivo, for their effects on D. discoideum. All the geminal bisphosphonates inhibited growth of Dictyostelium, although the effectiveness of individual compounds varied widely. When the bisphosphonates were ranked there was a remarkable similarity between the order of potency as inhibitors of growth of Dictyostelium and the order of potency as inhibitors of bone resorption. Thus, bisphosphonates with more complex side-chain structures, especially those containing a nitrogen group, were more potent than simple substituted bisphosphonates, some inhibiting Dictyostelium growth even at concentrations below 10 microM. It therefore appears that the mechanism by which bisphosphonates prevent Dictyostelium growth could be similar to the mechanism by which these compounds affect the activity of osteoclasts. Because the mechanisms of action of bisphosphonates on osteoclasts remains unclear, Dictyostelium may provide an additional model for studying the biochemical mode of action of bisphosphonates. Furthermore, these studies suggest that Dictyostelium may also be a convenient organism for rapid evaluation of potentially active bisphosphonates.

Animals↗
PubMed1994

Effects of sterigmatocystin and T-2 toxin on the induction of unscheduled DNA synthesis in primary cultures of human gastric epithelial cells.

Primary cultures of human gastric epithelial cells were tested for induction of unscheduled DNA synthesis (UDS) by sterigmatocystin (ST) and T-2 toxin. Autoradiographic results indicated that ST (10(-6)-10(-4)M) induced UDS in the presence of S9 activation system. The repair rates were 24-91% (net grains > or = 3) and 2-71% (net grains > or = 5). T-2 toxin did not induce UDS in this study.

Animals↗
PubMed1994

Three-dimensional structure of Schistosoma japonicum glutathione S-transferase fused with a six-amino acid conserved neutralizing epitope of gp41 from HIV.

The 3-dimensional crystal structure of glutathione S-transferase (GST) of Schistosoma japonicum (Sj) fused with a conserved neutralizing epitope on gp41 (glycoprotein, 41 kDa) of human immunodeficiency virus type 1 (HIV-1) (Muster T et al., 1993, J Virol 67:6642-6647) was determined at 2.5 A resolution. The structure of the 3-3 isozyme rat GST of the mu gene class (Ji X, Zhang P, Armstrong RN, Gilliland GL, 1992, Biochemistry 31:10169-10184) was used as a molecular replacement model. The structure consists of a 4-stranded beta-sheet and 3 alpha-helices in domain 1 and 5 alpha-helices in domain 2. The space group of the Sj GST crystal is P4(3)2(1)2, with unit cell dimensions of a = b = 94.7 A, and c = 58.1 A. The crystal has 1 GST monomer per asymmetric unit, and 2 monomers that form an active dimer are related by crystallographic 2-fold symmetry. In the binding site, the ordered structure of reduced glutathione is observed. The gp41 peptide (Glu-Leu-Asp-Lys-Trp-Ala) fused to the C-terminus of Sj GST forms a loop stabilized by symmetry-related GSTs. The Sj GST structure is compared with previously determined GST structures of mammalian gene classes mu, alpha, and pi. Conserved amino acid residues among the 4 GSTs that are important for hydrophobic and hydrophilic interactions for dimer association and glutathione binding are discussed.

Amino Acid Sequence↗
PubMed1994

Primary carcinoid of the renal pelvis.

We report a case of a surgically resected carcinoid of the renal pelvis diagnosed as papillary transitional cell carcinoma by light microscopy. Immunocytochemistry studies identified three immunoreactive products: cytokeratin, S-100 protein, and neuron-specific enolase. Ultrastructurally, dense core granules were seen. The histogenesis of renal pelvis carcinoid has not been clarified. This is the first documented case of a renal pelvis carcinoid.

Adult↗
PubMed1994

[Determination of plasminogen activator of the head and neck tumor tissue].

Fibrin plate was used to determine plasminogen activator (PA) of the head and neck tumor tissue. The results revealed: 1. The specific activity of PA of primary malignant tumor and neck lymphatic metastatic nodes were higher than that of normal tissue near cancer and benign tumor tissue; 2. The specific activity of PA was enhanced as advance of tumors in clinical stage. This study implicated that PA released from cancer cells can catalyze and convert plasminogen to plasmin, which results in tissue degradation, invasion and metastasis of tumor.

Carcinoma, Squamous Cell↗
PubMed1994

Primary chronic angle-closure glaucoma in Chinese--a clinical exploration of its pathogenesis and natural course.

Forty-three cases (86 eyes) of primary chronic angle-closure glaucoma were randomly selected. An additional 44 cases (77 eyes) of primary acute angle-closure glaucoma and 30 normal subjects (34 eyes) were also randomly enrolled as control groups for comparison in the clinical study. Ultrasonic biometric measurements of the anterior chamber depth, lens thickness and axial length of the eyeball were performed. Using an potic microgauge attached to the slit-lamp, the entrance of anterior chamber angle was also calculated. The clinical manifestations and the natural course, including the characteristic appearance of anterior chamber angle, the form of peripheral anterior synechia as well as the facility of outflow, were carefully investigated. There were significant differences in the biometric parameters of the anterior segment of eye among above three groups. The facts reveal that the anatomic features of eyeball, especially in the anterior segment differentiate from those of primary acute angle-closure glaucoma. Follow-up study for the early stage cases showed that topical administration of miotics and/or peripheral iridectomy can effectively prevent iris from forming peripheral anterior synechia and thus halt its development. The criteria of diagnosis and the principles of prevention and treatment at the early stage cases were presented. The pathogenesis was discussed. We emphasized that the progressive stage after intermittent attacks of primary acute angle-closure glaucoma should not be confused with primary chronic angle-closure glaucoma.

Adult↗
PubMed1993

Snapshots along the reaction coordinate of an SNAr reaction catalyzed by glutathione transferase.

The three-dimensional structures of a class mu glutathione transferase in complex with a transition-state analogue, 1-(S-glutathionyl)-2,4,6-trinitrocyclohexadienate, and a product, 1-(S-glutathionyl)-2,4-dinitrobenzene, of a nucleophilic aromatic substitution (SNAr) reaction have been determined at 1.9- and 2.0-A resolution, respectively. The two structures represent snapshots along the reaction coordinate for the enzyme-catalyzed reaction of glutathione with 1-chloro-2,4-dinitrobenzene and reveal specific interactions between the enzyme, intermediate, and product that are important in catalysis. The geometries of the intermediate and product are used to postulate reaction coordinate motion during catalysis.

Binding Sites↗
PubMed1993

Structure determination and refinement of human alpha class glutathione transferase A1-1, and a comparison with the Mu and Pi class enzymes.

The crystal structure of human alpha class glutathione transferase A1-1 has been determined and refined to a resolution of 2.6 A. There are two copies of the dimeric enzyme in the asymmetric unit. Each monomer is built from two domains. A bound inhibitor, S-benzyl-glutathione, is primarily associated with one of these domains via a network of hydrogen bonds and salt-links. In particular, the sulphur atom of the inhibitor forms a hydrogen bond to the hydroxyl group of Tyr9 and the guanido group of Arg15. The benzyl group of the inhibitor is completely buried in a hydrophobic pocket. The structure shows an overall similarity to the mu and pi class enzymes particularly in the glutathione-binding domain". The main difference concerns the extended C terminus of the alpha class enzyme which forms an extra alpha-helix that blocks one entrance to the active site and makes up part of the substrate binding site.

Amino Acid Sequence↗
PubMed1993

Tyrosine 115 participates both in chemical and physical steps of the catalytic mechanism of a glutathione S-transferase.

The participation of the hydroxyl group of tyrosine 115 in the catalytic mechanism of isoenzyme 3-3 of rat glutathione (GSH) S-transferase is implicated by x-ray crystallographic analysis of a product complex and confirmed by comparison of the catalytic properties of the native enzyme and the Y115F mutant. Tyrosine 115 is located in domain II of the protein (the xenobiotic substrate binding domain) and is the first residue in this domain to be shown to play a direct role in catalysis. The 1.8-A structure of isoenzyme 3-3 in complex with (9S,10S)-9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene, one of the diastereomeric products of the reaction of GSH with phenanthrene 9,10-oxide, indicates that the hydroxyl group of Tyr115 is within hydrogen-bonding distance of the 10-hydroxyl group of the bound product and, by implication, is proximal to the oxirane oxygen of the substrate in the Michaelis complex. Site-specific replacement of Tyr115 with phenylalanine has profoundly different effects on catalysis depending on the type of reaction and whether the rate-limiting step in catalysis is a chemical step or a physical step. Stopped flow measurements of the rate constants for product release and viscosity effects on the steady-state kinetics establish that the rate-limiting step in catalysis with phenanthrene 9,10-oxide (kcat = 0.4 s-1) is probably a chemical one, whereas the physical step of product dissociation (koff) is rate-limiting in the reaction of 1-chloro-2,4-dinitrobenzene (kcat = 20 s-1). The Y115F mutant is severely impaired in catalyzing the addition of GSH to phenanthrene 9,10-oxide (kcat = 0.0044 s-1), evidence that the -OH of Tyr115 provides electrophilic assistance in the epoxide ring opening. In contrast, the Y115F mutant is a better catalyst toward 1-chloro-2,4-dinitrobenzene (kcat = 72 s-1) than is the native enzyme. The enhanced rates of product release in the mutant are ascribed to the loss of hydrogen bonds between the -OH of Tyr115 and the side chain -OH and main chain NH of serine 209, interactions that block the channel to the active site or inhibit the segmental motion of the protein.

Amino Acid Sequence↗
PubMed1993

Noninvasive evaluation of right ventricular and pulmonary artery systolic pressures in patients with ventricular septal defects: simultaneous study of Doppler and catheterization data.

The method for evaluating right ventricular and pulmonary artery systolic pressures by subtracting the systolic pressure gradient across the ventricular septal defect from the cuff systolic blood pressure is documented. To confirm the reliability and accuracy of this method, simultaneous continuous wave Doppler echocardiography and left and right cardiac catheterization were performed in 66 patients with congenital ventricular septal defects. The comparisons between the Doppler-derived right ventricular or pulmonary artery systolic pressures and those measured by catheterization yielded an excellent correlation (r = 0.969, y = 1.035x - 3.627, SEE = 8.2 mm Hg, p < 0.001 and r = 0.972, y = 1.012x - 2.904, SEE = 7.6 mm Hg, p < 0.001), respectively. There was a close agreement between the Doppler-derived right ventricular or pulmonary artery systolic pressures and those measured by catheters, and the differences between the two measurements did not differ significantly from zero. It is concluded that Doppler echocardiography offers a reliable and accurate method for noninvasive assessment of right ventricular and pulmonary artery systolic pressures in patients with ventricular septal defects.

Adolescent↗