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Biomedical subjects

F Gao

Publications and source records attributed to F Gao.

At least 181 records · Page 10Linked to original sources

Relevance of chromatin features in the progression of esophageal epithelial severe dysplasia.

Since 1983, a long-term clinical trial of esophageal carcinoma chemoprevention has been conducted in a high-risk area in China. From this study, 25 esophageal severe dysplasia patients without therapy were selected for analysis. After 5-year follow-ups, 14 cases progressed to esophageal carcinoma, while the other 11 cases remained stable. Three Papanicolaou's smears were used for each case, including one from the esophageal cytological examination at the beginning, two from the re-examinations three and five years later respectively. About 100 visually normal intermediate cells were randomly collected per slide by high resolution image analysis. More than 100 features (morphologic, densitometric, textural) were extracted. The classifications were made by means of stepwise linear discriminate analysis at the single cell level as on the specimen level using up to ten features. In all three comparisons of patients with progression and with regression at time of diagnosis, three years after diagnosis and five years later, the correct cell classification rates were about 70%. The subsequent specimen classifications by means of the a posteriori probability (APOP) distribution of the cells in each case led to 80% correct classification. All selected features reflected the chromatin structure of nuclei. The result demonstrated that the chromatin structures of esophageal epithelial cells in severely dysplasic patients are different between cases with and without progression. These results suggest the possibility of the application of image analysis in the clinical trials to find the dysplasia patients with higher risk of progression, in order to reduce the number of patients for therapy.

Adult↗

Hypercholesterolemia impairs a detoxification mechanism against peroxynitrite and renders the vascular tissue more susceptible to oxidative injury.

Previous studies have shown that glutathione (GSH) plays a central role in the protection against peroxynitrite (ONOO-) toxicity. The present study evaluated the changes of the GSH cytoprotective system against ONOO- in hypercholesterolemia and determined the effects of carvedilol, a beta-blocker with free radical-scavenging activity, on these hypercholesterol-induced changes. New Zealand White rabbits were fed either a normal diet, a high-cholesterol diet, or a high-cholesterol diet supplemented with either carvedilol or propranolol. Eight weeks later, the rabbits were killed, and the thoracic aortas were isolated. Total GSH content of aortic tissue, vasorelaxation response of aortic rings to exogenous ONOO-, No regeneration from ONOO- by aortic homogenate, and ONOO(-)-induced aortic tissue injury were examined. Hypercholesterolemia decreased tissue GSH content (0.52 +/- 0.08 versus 0.86 +/- 0.04 mumol/g in control, P < .01), attenuated the vasorelaxation response to ONOO- (40 +/- 4.1% versus 76 +/- 3.2%, P < .01), reduced NO regeneration from ONOO- (387 +/- 40 versus 662 +/- 51 pmol, P < .01), and potentiated ONOO(-)-induced vascular tissue injury (37 +/- 4.4% versus 14 +/- 2.6% of increase in lactate dehydrogenase release after 3-morpholinosydnonimine exposure, P < .01). Treatment of the hypercholesterolemic rabbits with carvedilol, but not propranolol, significantly preserved tissue GSH content (0.79 +/- 0.05 mumol/g, P < .01 versus nontreated hypercholesterolemic rabbits), restored the vasorelaxation to ONOO- (61 +/- 2%, P < .01), increased NO regeneration from ONOO- (583 +/- 39 pmol, P < .01), and attenuated ONOO(-)-induced tissue injury (19 +/- 1.8%, P < .01). These results suggest that hypercholesterolemia impairs the GSH-mediated detoxification mechanism against ONOO- and renders the vascular tissue more susceptible to oxidative injury. Carvedilol, a novel vasodilating beta-blocker with antioxidant activity, significantly preserved this self-defense system and protected tissue from oxidant injury.

Animals↗

Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part I--The effects of heparin, protamine and propofol.

Neurone-specific enolase (NSE) and Sangtec 100 (S-100) (Sangtec Medical, Sweden) assays are designed for clotted samples, but when studying cerebral damage following cardiac surgery, perioperative samples will contain heparin and/or protamine. The lipid emulsion propofol is also frequently used during cardiac surgery and could affect the assays. We, therefore, studied the effects of heparin, protamine and propofol on the accuracy of NSE and S-100 assays in five healthy patients. Blood samples were taken and divided into four groups: normal saline was added to group A; heparin to group B; heparin followed by protamine to group C; and propofol to group D. NSE and S-100 concentrations were measured for all samples. Neither heparin, protamine nor propofol affected the accuracy of S-100 and NSE assays; therefore, samples can be taken throughout operations involving cardiopulmonary bypass without influencing the results.

Anesthetics, Intravenous↗

Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part II--Must samples be spun within 30 min?

Sangtec 100 (S-100) (Sangtec Medical, Sweden) and neurone-specific enolase (NSE) assays are showing promise in the assessment of cerebral damage following cardiopulmonary bypass (CBP). The manufacturer's instructions state, however, that samples must be spun and frozen within 30 min, which is inconvenient for serial studies. We, therefore, investigated whether strong blood samples at room temperature (RT) or 4 degrees C for up to 48 h affected the measured levels. Blood samples were taken before and after CBP in six patients and stored for 15 min, 4, 8, 24 or 48 h at RT or 4 degrees C. S-100 and NSE levels did not alter in either 'before surgery' or CPB samples when stored for up to 48 h at 4 degrees C. There was a small, nonsignificant rise when stored at RT. Samples may, therefore, be collected throughout long operations or stored overnight without affecting NSE or S-100 plasma levels.

Blood Preservation↗

Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part III--Dose haemolysis affect their accuracy?

Neurone-specific enolase (NSE) and Sangtec 100 (S-100) are useful for detecting cerebral damage during cardiopulmonary bypass (CPB). However, red cells contain NSE, and the haemolysis frequently caused by CPB could produce a false rise in NSE; S-100 is not found in red cells and should not be affected. We, therefore, compared the effects of haemolysis on NSE and S-100 to see if correction was necessary and possible. From seven patients, serial dilutions of haemolysed red cells were added to plasma (1/64-1/2048), measured for absorption at 540 nm and assayed for NSE and S-100. S-100 concentrations showed no change with haemolysis. Measured NSE increased significantly with haemolysis > 1/512 (an increase of 6.6 micrograms/ml): a correction formula is presented. In 39/48 patients after CPB, mean haemolysis was < 1/256 and would not need any correction. NSE and S-100 assay can, therefore, be used throughout CPB, which allows both glial and neuronal damage to be studied.

Artifacts↗

Erosion process of light-cured and conventional glass ionomer cements in citrate buffer solution.

The aim of this study was to clarify the erosion behavior of light-cured glass ionomer cement. One light-cured glass ionomer cement and two conventional chemically-cured glass ionomer cements were immersed in citric acid buffer solutions of pH 4 and pH 6. Fluoride release was almost the same in both types of cements, irrespective of pH. The amounts of other species eluted, such as Al, Sr, Si and P2O5 were smaller in the light-cured glass ionomer cement than in the conventional ones at pH 4. The amounts of species eluted at pH 6 were almost the same in both types of cement. Dissolution of the light-cured cement in pH 4 solution was controlled by the diffusion of the eluted species in the cement matrix. On the other hand, dissolution of the conventional cements was controlled by both diffusion and surface reaction. The surface features of the cements after erosion corresponded well to the dissolution mechanism. In pH 6 solution, dissolution of the cements was mainly controlled by diffusion of the species in the cement.

Buffers↗

[Correlation of tumor microvesseldensity with prognosis in osteogenic sarcoma].

OBJECTIVE: To investigate the relationship between tumor angiogenesis and clinical pathology, as wel as the prognosis in osteosarcoma. METHODS: Intratumoral microvessel density (MVD) in 70 cases of osteosarcoma was assessed immunohistochemically by using the specific endothelial cell markers F VIII-RA and CD31. RESULTS: There was no correlation between the MVD and the tumor size, Price's grade, as well as Dahlin's classification; however, significant correlation was found between the MVD and the neoplastic osteoid classification, new WHO classification in 1993, as well as the proliferating cell nuclear antigen (PCNA) labelling index. Microvessel counts were associated with overall survival by Kaplan-Meier analysis. An average vessal count of less than 31 (x 200) suggested a better survival, but a higher vessel count of more than 31 (x 200) showed a trand to worse the overall survival. CONCLUSION: The results suggest a significant relationship between MVD and prognosis; moreover, MVD may be a useful prognostic indicator in osteosarcomas.

Bone Neoplasms↗

[Endovascular treatment of brain arteriovenous malformation].

Eighteen patients with arteriovenous malformations (AVMs) of the brain were treated with endovascular techniques between 1993 and 1996. The following angiograms showed complete obliteration of the nidus in 2 patients, 70%-90% reduction in nidus volume in 5, 50%-70% reduction in 3, and < 50% in the remaining 3. Two patients suffered from moderate neurologic deficits after embolization. One week after the treatment, 4 patients with superficial AVMs underwent surgery, and 2 with deep-situated AVMs received gamma-knife therapy. 14 patients were followed up, suffered from more frequent epilepsy, and 1 had intracranial haemorrhage 6 months after embolization. A few AVMs can be cured by endovascular embolization. In regard to some large AVMs or AVMs situated at important functional areas, embolization can facilitate surgery and radiotherapy afterwards.

Adolescent↗

[An immunohistochemical study on ciliary sulcus tissue in cases of intraocular lens implantation with ciliary sulcus suture fixation].

OBJECTIVE: To observe abnormal cell multiplication in rabbits ciliary sulcus with posterior chamber intraocular lens (PC-IOL) implantation and ciliary sulcus fixation technique. METHODS: 96 New Zealand rabbits were implanted with PC-IOL, and they were divided into two groups: one with ciliary sulcus suture fixation and the other without the suture fixation. The eyeballs were extracted at the following postoperative times: 1/2, 1, 2, 3 months. The reactions of the proliferating cell nuclear antigen (PCNA) in ciliary sulcus of the rabbits were studied with immunohistochemistry technique in the above two groups and the normal control group. RESULTS: There was no abnormal proliferating cell reaction in ciliary sulcus of the rabbits with the two methods of PC-IOL implantation techniques. CONCLUSIONS: IOL ciliary sulcus suture fixation is a convenient method for PC-IOL implantation under the circumstance when rupture of the posterior capsule occurs intraoperatively or in the second stage implantation.

Animals↗

Development and DNA synthesis in the retina of chick embryo observed by light and electron microscopic radioautography.

The incorporation of 3H-thymidine into DNA was examined in the chick embryo retina in early development during the period of the optic vesicle formation (day 2) before the formation of the basic layers of retina (day 7) by means of light and electron microscopic radioautography. Labeling index with 3H-thymidine reached the maximum on day 2 and declined thereafter. The patterns of localization of labelled cells and average grain counts were compared in the anterior, equatorial and posterior regions of the retina. On day 2, more labelled cells were found in the posterior region than the other two regions of the retina. Most of the labelled cells were found in the outer portion of the retinal layer throughout the retina. On day 3, most labelled cells were found in the anterior region and decreased in the posterior one. On day 4, labelled cells dominated in the anterior and equatorial regions. In these two regions, more labelled cells were present in the outer portion of the retinal layer, while in the posterior region these cells were seen in the inner portion of the retinal layer.

Animals↗

Isolation and characterization of vibrational spectra of individual heme active sites in cytochrome bc1 complexes from Rhodobacter capsulatus.

Resonance Raman spectra of bc1 complexes and isolated c1 subunit from Rhodobacter capsulatus have been obtained using a variety of excitation wavelengths. Spectra obtained via Q-band excitation of bc1 complexes in different redox states were separated to yield the individual vibrational spectra of each of the three heme active sites. Hemes bH and c1 exhibit vibrational spectra typical of b- and c-type hemes, respectively. In contrast, the spectrum of heme bL is anomalous with respect to those of other hemes b. The isolated spectra were also used to assess the effects of inhibitor binding on the local structural environments of the hemes. Neither antimycin nor myxothiazol binding produces dramatic structural perturbations at the hemes. Heme c1 is completely unaffected by the presence of either inhibitor. The vibrational spectra of hemes bH and bL are slightly altered by antimycin and myxothiazol binding, respectively.

Antimycin A↗

Metabolically programmed polyamine analogue antidiarrheals.

The design, synthesis, and testing of a novel class of antidiarrheal drugs based on a tetraamine pharmacophore are reported. While N1,N14-diethylhomospermine (DEHSPM) (5 mg/kg) completely prevents diarrhea in rodents, tissue distribution studies demonstrated that the principal metabolite of DEHSPM, homospermine (HSPM), accumulates and persists in tissues for a protracted period of time. This accumulation accounts for a large part of the chronic toxicity of DEHSPM. Thus a major objective was to develop a metabolically labile analogue of DEHSPM which retained the desirable biological properties of the parent drug. Hydroxyl groups, sites vulnerable to further metabolic transformation, were introduced into the external aminobutyl segments providing N1,N14-diethyl-(3R),(12R)-dihydroxyhomospermine [(HO)2-DEHSPM]. The design concept was assisted by molecular modeling, which predicted that (HO)2DEHSPM would have a Ki for polyamine transport essentially identical with that of DEHSPM. The experimentally measured Ki and also the observed values of other biological properties of (HO)2DEHSPM were in fact identical with those of DEHSPM, including IC50 against L1210 cells, impact on the NMDA receptor, and impact on L1210 native polyamine pools. Most significantly, however, there was no accumulation of the dideethylated metabolite in tissues from mice treated chronically with (HO)2DEHSPM, and (HO)2DEHSPM was 3-fold less toxic than DEHSPM. Finally, (HO)2DEHSPM completely prevented diarrhea in the castor oil-treated rat model at a dose of 5 mg/kg, just as did DEHSPM.

Animals↗

Antitumor activity of the Cu(II)-mitoxantrone complex and its interaction with deoxyribonucleic acid.

The effect of the Cu(II)-mitoxantrone complex on the DNA synthesis of HL-60 human leukemia cells has been studied by the technique of isotopic liquid scintillation. The results indicated that the complex shows a stronger ability to inhibit DNA synthesis of the tumor cells, and thus it may become a better antitumor drug. The interaction of mitoxantrone and its Cu(II) complex was studied by the methods of electrochemistry and spectroscopy. The complex gives rise to more changes on the conformation and the double-helical structure of DNA; this is closely related to the antitumor mechanism of the complex.

Animals↗

Comparison of the antitumor activity of bryostatins 1, 5, and 8.

Bryostatin 1, a macrocyclic natural lactone isolated from a marine Bryozoan, has undergone phase I testing in humans. Side effects of treatment have included muscle pain and joint aches, a transient decrease in platelets, and the release of tumor necrosis factor alpha (TNF alpha) and IL-6 into the blood stream. In animals, anticancer activity has been demonstrated against murine leukemias, lymphomas, melanomas, and sarcomas. The mechanism of action of this compound depends in part on its ability to activate protein kinase C. To determine the biologic activity and toxicity of other members of the family of bryostatin compounds, we studied the ability of bryostatins 5 and 8 to inhibit the growth of murine melanoma K1735-M2. Bryostatins 1, 5, and 8 induced equivalent inhibition of melanoma growth, but bryostatins 5 and 8 induced less weight loss than bryostatin 1 (P < 0.001). Neither the injection of an antimurine TNF alpha antibody nor an adenovirus, which produces a mutated TNF receptor inhibiting TNF alpha activity, into mice had any effect on either bryostatin-induced weight loss or melanoma tumor growth inhibition. Using a novel competition assay, the levels of bryostatin in the plasma were measured. The approximate half-life (t1/2) of bryostatin was 8.62 min, the clearance (Cl) 3.53 ml/min and the AUC 322.20 nmol/l min. A similar result was obtained with each bryostatin analog. These results suggest that human testing of additional bryostatin analogs may yield compounds with similar antitumor activity but decreased side effects. A novel assay to measure the level of all bryostatins in the plasma of patients undergoing treatment is described.

Animals↗

The chloroplast ATP synthase: structural changes during catalysis.

This article summarizes some of the evidence for the existence of light-driven structural changes in the epsilon and gamma subunits of the chloroplast ATP synthase. Formation of a transmembrane proton gradient results in: (1) a changed in the position of the epsilon subunit such that it becomes exposed to polyclonal antibodies and to reagents which selectively modify epsilon Lys109; (2) enhanced solvent accessibility of several sulfhydryl residues on the gamma subunit; and (3) release/exchange of tightly bound ADP from the enzyme. Theses and related experimental observations can, at least partially, be explained in terms of two different bound conformational states of the epsilon subunit. Evidence for structural changes in the enzyme which are driven by light or nucleotide binding is discussed with special reference to the popular rotational model for catalysis.

Catalysis↗

A light and electron microscopic radioautographic study on RNA synthesis in the retina of chick embryo.

The incorporation of 3H-uridine into RNA of chick embryo retina was studied by light and electron microscopic radioautography. The numbers of silver grains were counted over the nucleus, nucleolus and cytoplasm of the cells in three different regions of the same retina of 2, 3, 4, and 7 day chick embryos. The results showed an increase of 3H-uridine incorporation from embryonic day 2 to 7. In every stage of development of the chick embryo retina, the number of silver grains was higher in the anterior than in the other two regions of the retina. In the three cell compartments of every embryo group, the number of silver grains was higher in the nucleus than in the nucleolus and cytoplasm. The results show further that the grains were less in the cytoplasm of the retinal cells of the day 2 embryo group and higher in the other groups especially in the day 7 embryos. Ultrastructural changes were also observed during the studied period of retina development.

Animals↗