Biomedical subjects

X Fu

Publications and source records attributed to X Fu.

At least 91 records · Page 5Linked to original sources

PubMed1997

Titration kinetics of Asp-85 in bacteriorhodopsin: exclusion of the retinal pocket as the color-controlling cation binding site.

The spectrum (the purple blue transition) and function of the light-driven proton pump bacteriorhodopsin are determined by the state of protonation of the Asp-85 residue located in the vicinity of the retinal chromophore. The titration of Asp-85 is controlled by the binding/unbinding of one or two divalent metal cations (Ca2+ or Mg2+). The location of such metal binding site(s) is approached by studying the kinetics of the cation-induced titration of Asp-85 using metal ions and large molecular cations, such as quaternary ammonium ions, R4N+ (R = Et, Pr, a divalent 'bolaform ion' [Et3N+-(CH2)4-N+Et3] and the 1:3 molecular complex formed between Fe2+ and 1,10-phenanthroline (OP). The basic multi-component kinetic features of the titration, extending from 10(-2) to 10(4) s, are unaffected by the charge and size of the cation. This indicates that cation binding to bR triggers the blue --> purple titration in a fast step, which is not rate-determining. In view of the size of the cations involved, these observations indicate that the cation binding site is in an exposed location on, or close to, the membrane surface. This excludes previous models, which placed the color-controlling Ca2+ ion in the retinal binding pocket.

Aspartic Acid↗

PubMed1997

Time-resolved titrations of ASP-85 in bacteriorhodopsin: the multicomponent kinetic mechanism.

The Asp-85 residue, located in the vicinity of the retinal chromophore, plays a key role in the function of bacteriorhodopsin (bR) as a light-driven proton pump. In the unphotolyzed pigment the protonation of Asp-85 is responsible for the transition from the purple form (lambdamax = 570 nm) to the blue form (lambdamax = 605 nm) of bR (pKa = 3.5 in 20 mM NaCl). The Purple <=> Blue transition can also be induced by deionization (cation removal). These color changes offer a unique opportunity for time resolving the titration of a protein residue using conventional stopped-flow methodologies. We have studied the Purple <=> Blue equilibration kinetics in bR by exposing the system to pH and to cation jumps. Independently of the equilibration direction (Purple-->Blue or Blue-->Purple) and of the inducing concentration jump ([H+] or [cation]), the kinetics are found to exhibit analogous multicomponent features. Analysis of the data over a range of cation concentrations and pH values leads to the conclusion that the rate-determining step in the overall titration of Asp-85 is proton translocation through a specific proton channel. The multicomponent kinetics, extending over a wide time range (10(-2)-10(4) s), are accounted for in terms of a pH-dependent heterogeneity of proton channels. A model is presented in which the relative weight of four proton channels is determined by the state of protonation of two interacting, channel-controlling, protein residues A1 and A2. These findings bear on the mechanism of the vectorial proton translocation associated with the photocycle of bR.

Aspartic Acid↗

PubMed1997

Glucocorticoid regulation of natural cytotoxicity: effects of cortisol on the phenotype and function of a cloned human natural killer cell line.

The ability of glucocorticoids to suppress cellular immune functions, including the cytotoxic activity of natural killer cells, is well known. However, the molecular mechanism(s) of glucocorticoid-mediated suppression of cellular cytotoxicity mediated by natural killer cells is not understood. We have investigated the effects of cortisol on protein expression and cytotoxic function of natural killer cells using NK3.3, a well-characterized, cloned human natural killer cell line. Cortisol, at concentrations up to 2 microM, does not significantly alter the viability or proliferative capacity of NK3.3 cells. However, micromolar concentrations of cortisol induce the expression of a small set of proteins which are not synthesized by NK3.3 cells in the absence of cortisol, and repress the synthesis of another set of proteins including several phenotypic determinants and cytokines. In the presence of added cortisol, the synthesis of perforin mRNA was partially repressed. However, the most striking effect of cortisol on this NK clone was its repression of granzyme A synthesis. In conjunction with the downregulation of adhesion proteins, NK3.3 cells cultured in the presence of cortisol exhibit a reduced capacity to form conjugates with K562 target cells. Whereas cortisol treatment of NK3.3 cells causes an approximately 50% decrease in their ability to form conjugates with K.562 target cells, the cytotoxic function of these cells is completely abolished under the same conditions. This first report of hormonal regulation of granzyme expression and the strong correlation between granzyme A repression and cytotoxic function suggests that cortisol may regulate NK function by repression of granzyme A synthesis. In addition to demonstrating the significant influence of cortisol on natural killer cell function, these studies provide a model system for elucidation of molecular mechanism(s) whereby glucocorticoids repress cellular immune function, especially with respect to natural killer cells.

Anti-Inflammatory Agents↗

PubMed1997

Psammaplysin F, a new bromotyrosine derivative from a sponge, Aplysinella sp.

A new member of the psammaplysin family, psammaplysin F (6) has been isolated from an undescribed species of Aplysinella sponge, along with the four known psammaplysins A-C (1-3) and E (5). The structure of psammaplysin F was determined by spectral analysis.

Animals↗

PubMed1997

Anisomycin and verapamil influence the action of progesterone on regulation of term human myometrial contractile activity.

OBJECTIVE: Progesterone has been shown to have both stimulatory and inhibitory effects on term human myometrial contractile activity. The mechanisms involved in this action of progesterone are still poorly understood. DESIGN: Myometrial tissues were obtained from the lower uterine segment at elective Caesarean section of 30 term pregnant women. The contractile activity of muscle strips was measured by a superfusion technique and protein synthesis evaluated by [3H]-leucine incorporation. RESULTS: [3H]-leucine incorporation into term myometrial strips was not affected by progesterone (10 mumol/l), but was markedly reduced by the protein synthesis inhibitor anisomycin (P < 0.05). However, progesterone increased frequency and tonus of contractions and reduced the activity-area of contractions (P < 0.01). Anisomycin (100 mumol/l) did not change these effects or the spontaneous contractile activity. Removal or extracellular Ca2+ or addition of the L-type calcium channel blocker verapamil prevented the spontaneous as well as the progesterone-induced contractions, but had less pronounced effects on contractions initiated by oxytocin. CONCLUSION: The results indicate that the actions of progesterone on term myometrial contractile activity occur without protein synthesis and that increased Ca2+ influx or decreased outward transport of Ca2+ may play a possible role)

Adult↗

PubMed1997

Basic fibroblast growth factor reduces the gut and liver morphologic and functional injuries after ischemia and reperfusion.

OBJECTIVE: To explore the possible effects of basic fibroblast growth factor (bFGF) on ischemic gut and liver injuries after trauma. METHODS: Animal models of superior mesenteric artery occlusion (45 minutes) and reperfusion (3 days) were used in this study. Seventy-two Wistar rats were divided into three groups of 24 rats each. The animals in bFGF-treated group were injected with 4 microg bFGF/rat in 0.15 mL normal saline solution containing heparin 0.1% (w/v) through the jugular vein at the onset of reperfusion. In the normal saline control group, all rats received the same vehicle, but without bFGF. Group 3 (sham-operated) underwent the same laparotomy procedure, but without superior mesenteric artery occlusion. Liver function parameters, the levels of serum tumor necrosis factor alpha, nitric oxide, superoxide dismutase, malondialdehyde (MDA), tissue bacterial examination, and pathologic study were used to evaluate the results. RESULTS: In bFGF-treated rats, the amounts of serum alanine transaminase and aspartate aminotransferase and serum tumor necrosis factor-alpha were reduced significantly at 6, 24, and 48 hours when compared with normal saline-treated rats. However, the changes in nitric oxide, superoxide dismutase, and MDA varied from each other as a function of time after injury. The amounts of nitric oxide were increased significantly at 6 hours in intestine in normal saline-treated rats and in liver in bFGF-treated rats (p < 0.05). At 6 hours after reperfusion, the activity of superoxide dismutase in normal saline-treated rats were much lower in liver than those in bFGF-treated and sham-operated rats (p < 0.05), but the levels of MDA were increased in intestine in bFGF-treated rats and in liver in normal saline-treated rats when compared with sham-operated rats (p < 0.05). At 24 hours, the levels of MDA in normal saline-treated rats were much higher than those in both bFGF and sham-operated rats (p < 0.05). Bacterial examination revealed that the ratio and the amounts of bacterial translocation from gut to liver, spleen, and mesenteric lymph nodes in bFGF-treated rats were much lower than those in normal saline-treated rats. The results of pathologic study support the assumption that bFGF provided protective effects against reperfusion injury. CONCLUSIONS: Intravenous administration of bFGF may benefit in reducing gut and liver injuries after ischemia and reperfusion. The mechanisms of those effects may involve mitogenic and nonmitogenic effects of bFGF.

Animals↗

PubMed1997

E2a-Pbx1 induces aberrant expression of tissue-specific and developmentally regulated genes when expressed in NIH 3T3 fibroblasts.

The E2a-Pbx1 oncoprotein contains the transactivation domain of E2a joined to the DNA-binding homeodomain (HD) of Pbx1. In mice, E2a-Pbx1 transforms T lymphoblasts and fibroblasts and blocks myeloblast differentiation. Pbx1 and E2a-Pbx1 bind DNA as heterodimers with other HD proteins whose expression is tissue specific. While the transactivation domain of E2a is required for all forms of transformation, DNA binding by the Pbx1 HD is essential for blocking myeloblast differentiation but dispensable for fibroblast or T-lymphoblast transformation. These properties suggest (i) that E2a-Pbx1 causes cellular transformation by activating gene transcription, (ii) that transcription of E2a-Pbx1 target genes is normally regulated by ubiquitous Pbx proteins and tissue-specific partners, and (iii) that DNA-binding mutants of E2a-Pbx1 activate a subset of all gene targets. To test these predictions, genes induced in NIH 3T3 fibroblasts by E2a-Pbx1 were identified and examined for tissue- and stage-specific expression and their differential abilities to be upregulated by E2a-Pbx1 in NIH 3T3 fibroblasts and myeloblasts and by a DNA-binding mutant of E2a-Pbx1 in NIH 3T3 cells. Of 12 RNAs induced by E2a-Pbx1, 4 encoded known proteins (a J-C region of the immunoglobulin kappa light chain, natriuretic peptide receptor C, mitochondrial fumarase, and the 3',5'-cyclic nucleotide phosphodiesterase, PDE1A) and 5 encoded new proteins related to angiogenin, ion channels, villin, epidermal growth factor repeat proteins, and the human 2.19 gene product. Expression of many of these genes was tissue specific or developmentally regulated, and most were not expressed in fibroblasts, indicating that E2a-Pbx1 can induce ectopic expression of genes associated with lineage-specific differentiation.

3T3 Cells↗

PubMed1997

[The expression of proliferating cell nuclear antigen in breast phylloides cystosarcoma and its significance].

OBJECTIVE: To investigate the expression of proliferating cell nuclear antigen (PCNA) in breast phylloides cystosarcoma and its clinicopathological signification. METHODS: Immunohistochemistry (SP method) with monoclonal antibodies PC10 against PCNA was performed in 100 cases of phylloides cystosarcoma and 39 cases of adenofibroma. RESULTS: The positive rate of PCNA in phylloides cystosarcoma was 86%. The average PCNA index (PI) of phylloides cystosarcoma was significantly different among every histologic grading (F = 85.33, P < 0.01). The degree of differentiation was lower, the PI was higher. The PI was closely correlated with histologic grading (r's = 0.77). The PI in grade I phylloides cystosarcoma was higher than that in the group of adenofibroma with abundant mesenchymal cells (t = 3.42, P < 0.01). There was only a low correlation between PI and mitotic figures in phylloides cystosarcoma (r = 0.39). CONCLUSIONS: These findings suggest that the detection of PCNA has considerable practical value in reflecting the proliferation of activity of phylloides cystosarcoma, assisting the pathologists to make histologic grading; distinguishing the malignancy from benign ones (differential diagnosis) and evaluating the prognosis.

Adenofibroma↗

PubMed1997

[Uterine activity in active phase].

This study was designed to understand the uterine activity (UA) in normal labor. 43 nulliparous women(33 in normal course of labor and 10 in abnormal course of labor) were in the active phase of spontaneous labor with cephalic presentation for vaginal delivery. An open-end fluid filled intrauterine catheter connected to a pressure transducer was used to measure the uterine contraction intensity, frequency and duration. UA was quantified by means of Montevideo Unit (MU) and Uterine activity integral(UAI). The receiver operator characteristic(ROC) curve defined the cut-off points of UA between normal labor and abnormal labor. The results showed that MU and UAI were correlated with the rate of cervial dilatation in the active phase of labor (r = 0.3734 and 0.3502 respectively, P < 0.05). There was a strong correlation between MU and UAI (r = 0.7173, P < 0.001). The mean of UA in normal labor as MU = 226(s = 68.45) mmHg/15 min. UAI = 901(s = 258.02) kPa/15 min. The minimum of UA to normal labor in MU was 170 mmHg/15 min, of UAI 650 kPa/15 min. The study suggests that quantification of UA is very useful in the management of labor, especially in the proper use of oxytocin in cases abnormal labor.

Female↗

PubMed1997

[Immunohistochemical study of c-erbB-2 and p53 protein in breast papillomatosis and its malignant transformation].

OBJECTIVE: To evaluate the levels of c-erbB-2 and p53 protein in different stages of papillomatosis of breast and its malignant transformation and value for early diagnosis. METHODS: Levels of c-erbB-2 and p53 protein were detected by immunohistochemistry in 184 paraffin-embeded blocks. RESULTS: c-erbB-2 protein expression was seen in all stages of papillomatosis with different degrees of proliferation and in tissues undergone malignant transformation. The rate of overexpression increased with the degree of proliferation. The p53 protein expression was not found in papillomatosis with mild to severe proliferation. It was only overexpressed in 3.5% of carcinoma arising from papillomatosis, but increased to 25% when invasion occurred. CONCLUSION: c-erbB-2 assay may be helpful for detection of early malignant change of the highly proliferative papillomatosis, especially when histopathological evidence of malignancy is still lacking. p53 protein is of no significant diagnostic value in these lesions.

Breast Neoplasms↗

PubMed1997

[Pathological study of en bloc breast sections in papillomatosis and its malignant transformation].

OBJECTIVE: To investigate the characteristics of breast papillomatosis, its malignant transformation and relation with main ductal papilloma. METHODS: A histopathological study by en bloc breast subserial sections was performed on 14 cases of highly proliferative papillomatosis and 22 cases of carcinoma arising from the highly proliferative papillomatosis. RESULTS: The two types of lesions were widely scattered over the sections, covering more than two quadrants in 71.4% (10/14) and 63.3% (14/22) of the breast, respectively. Crisscross and histological transition of the two lesions were observed frequently in the sections of carcinoma arising from the highly proliferative papillomatosis. These two kinds of lesion often coexisted with main ductal papilloma. CONCLUSION: Papillomatosis is a breast precancerous lesion and it may have similar pathogenetic mechanism as main ductal papilloma.

Breast Neoplasms↗

PubMed1997

Gallstones and their chemical types in relation to serum lipids and apolipoprotein levels.

OBJECTIVE: To determine the profile of lipidemia in patients with gallstones and the characteristics of lipidemia in different kinds of gallstone in gallbladder for predicting high risk subjects predisposed to gallstone formation by means of some serum parameters. METHODS: Serum lipids and apolipoproteins levels in 47 patients with stone in gallbladder (stone group) were compared with those in 19 inpatients without stone (control group). The characteristics of lipidemia in different kinds of gallbladder stones were also compared. RESULTS: Serum apolipoprotein (Apo) A1, C2 and E levels in the stone group significantly increased as compared with the control group (P < 0.01), but there were no statistically significant differences in TC, TG, LDL-C, HDL-C, HDL-C/TC, LDL-C/HDL-C, Apo A2, B and C3 and Apo A1/Apo B levels between the stone and control groups (P > 0.05). Increased levels of serum LDL-C and Apo B and the LDL-C/HDL-C ratio (P < 0.05) were characterized as an index of cholesterol stones, while elevated levels of serum TG and Apo C2 (P < 0.05) as an index of pigment stones. CONCLUSIONS: Serum apolipoproteins might be more sensitive parameters as compared with serum lipids in distinguishing patients with stones from subjects without stones. There are different profiles of serum lipids and apolipoproteins in different chemical types of gallbladder stones.

Adult↗

PubMed1997

Percutaneous transluminal coronary angioplasty for acute myocardial infarction: initial experience in 43 cases.

OBJECTIVE: To evaluate the initial experience with the use of percutaneous transluminal coronary angioplasty (PTCA) in the set of acute myocardial infarction (AMI). METHODS: Between October 1993 and April 1996, PTCA was performed in 43 patients (34 male, 9 female) with initial onset of AMI. These patients ranged in age from 40 to 74 years (mean +/- SD, 60.3 3 +/- 9.2). Primary PTCA was performed in 16, rescue PTCA in 8, and semi-elective PTCA in 19 patients. RESULTS: The initial success was achieved in 95.3% (41/ 43). Failed angioplasty occurred in 2 patients, with acute reocclusion after rescue PTCA (this patient died of cerebral stroke 3 days later) in one patient, and small local intimal dissection during semi-elective PTCA in another patient. CONCLUSION: PTCA was a safe and effective approach in the treatment of AMI in the present study patients, with a high primary success and low acute complication rate.

Adult↗

PubMed1997

[Effects of bFGF on succinate dehydrogenase level and oxygen consumption of skin flap in rats].

To investigate the effects of basic fibroblast growth factor (bFGF) on necrosis rate, succinate dehydrogenase level and oxygen consumption of the skin flap, 18 Wistar rats were divided into 2 groups. Caudally based skin flap was raised on the back of each rat. Nine micrograms bFGF or normal saline with heparin was instilled under the flaps respectively after closure of the wounds. After 7 days, the necrosis rate of each wound was measured. The result showed that in bFGF group, the average necrosis rate of skin flap was 18.2%, less than that of the control group (37.14%). Succinate dehydrogenase content and oxygen consumption in bFGF group were higher than those of the corresponding sites in the control group (P < 0.05). It was suggested that the use of bFGF resulted in the decrease rate of necrosis of skin flap, and it maintained higher succinale dehydrogenase level and oxygen consumption. It was concluded that bFGF would probably be valuable for clinical use.

Animals↗

PubMed1996