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Biomedical subjects

E Zhang

Publications and source records attributed to E Zhang.

46 records · Page 3Linked to original sources

K-ras mutation in sputum of patients with or without lung cancer.

K-ras mutation appears in about 60% of patients with non-small-cell lung cancer (NSCLC). This frequency and its presence in normal appearing tissues point to the potential of ras oncogene mutation to serve as a good biomarker. Using enriched PCR (EPCR), which enables the detection of one mutant allele in the presence of 10,000 normal alleles, we have determined the frequency of mutant ras alleles in the sputum samples of patients with or without lung cancer. Samples were collected from 17 patients with NSCLC and from 40 controls who suffered from non-oncological lung diseases, including bronchitis, asthma, and pneumonia. Of the 37 samples obtained from patients with lung cancer, 18 were found to harbor ras oncogene mutations (48%). Of the 40 cases that were free of lung cancer, five were found to harbor this mutation (12.5%). The difference between the two frequencies was found to be significant (P < 0.01). These findings indicate that (a) K-ras oncogene mutation can be identified in routinely obtained sputum samples of patients who may be at risk of developing lung cancer and (b) the higher frequency of these mutations in samples of patients with lung cancer points to the potential use of the ras mutation as a biomarker for either exogenous or endogenous exposure to carcinogens. Thus, the ability to examine sputum provides a powerful and convenient source of sampling and may be adapted for future large-scale screening.

Adult↗

[Influence of HPD on immunological functions in patients with nasopharyngeal carcinoma treated by radiotherapy].

Seventy-eight patients with nasopharyngeal carcinoma were equally divided into two groups: 39 patients were treated by HPD plus radiation and 39 patients by radiation alone. Immunological functions were evaluated in each patient before and after radiation. The results showed that (1) in patients treated by RPD and radiation, no statistical difference was observed on immunological functions before and after treatment; (2) in patients treatd by radiation alone, the immunological functions, including OKT3, OKT4, OKT4/OKT8 ratio and lymphocyte transformation, were significantly decreased after treatment. These findings indicate that the immunological functions in patients with nasopharyngeal carcinoma could be protected by HPD during radiotherapy.

Adolescent↗

A new staging system for nasopharyngeal carcinoma in China.

PURPOSE: An accurate and rational nasopharyngeal carcinoma (NPC) stage based on images is proposed. METHODS AND MATERIALS: Four hundred and twenty-one cases of NPC, treated in the Cancer Hospital, Sun Yat-sen University of Medical Sciences (SUMS), with computed tomography scanning before initial radiotherapy, are analyzed. Important prognostic factors that form the basis of the new staging system are screened out by means of Cox model and clinical experiences. Survival curves of various kinds of T and N stages are compared by computer simulation. A new staging system is proposed by studying the traditional staging systems such as the AJC, UICC, Ho's and Changsha systems. RESULTS: According to the new staging criteria, the 5-year survival rates for Stages I-IV are 89.7%, 75.9%, 51.3%, and 22.2%, respectively. CONCLUSION: This new clinical staging for NPC based on a large amount of cases multivariate analysis is satisfactory and widely used in China.

Adult↗

Catalytic metal ion binding in enolase: the crystal structure of an enolase-Mn2+-phosphonoacetohydroxamate complex at 2.4-A resolution.

Enolase, a glycolytic enzyme that catalyzes the dehydration of 2-phospho-D-glycerate (PGA) to form phosphoenolpyruvate (PEP), requires two divalent metal ions per active site for activity. The first metal ion, traditionally referred to as "conformational", binds in a high-affinity site I. The second metal ion, "catalytic", binds in site II only in the presence of a substrate or substrate analogue and with much lower affinity for the physiological cofactor Mg2+. While the high-affinity site has been well characterized, the position of the lower affinity site has not been established so far. Here, we report the structure of the quaternary complex between enolase, the transition-state analogue phosphonoacetohydroxamate (PhAH), and two Mn2+ ions. The structure has been refined by using 16 561 reflections with F/sigma (F) > or = 3 to an R = 0.165 with average deviations of bond lengths and bond angles from ideal values of 0.013 A and 3.1 degrees, respectively. The "catalytic" metal ion is coordinated to two oxygen atoms of the phosphono moiety of PhAH and to the carbonyl oxygen of Gly37. Most likely, disordered water molecules complement its coordination sphere. The interaction with the site II metal ion must stabilize negative charge on the phosphate group and produce electron withdrawal from carbon 2 of the substrate, facilitating proton abstraction from carbon 2, the rate-limiting step in the catalytic process. The Gly37 residue is located in the flexible loop Ser36-His43, which assumes an "open" conformation in the absence of substrate and a "closed" conformation in the presence of a substrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

Crystallization at low salt concentration and alkaline pH and preliminary crystallographic data for a monoclinic form of yeast enolase.

Yeast enolase (2-phospho-D-glycerate hydrolyase, E.C. 4.2.1.11) has been crystallized by vapor diffusion from a solution containing 22% PEG 4000, 100 mM Tris buffer pH = 9.3, 200 mM Li(2)SO(4). The crystals are monoclinic with a = 122.5, b = 111.8, c = 63.7 A, beta = 95.6 degrees, space group P2(1) and two dimeric molecules are present in an asymmetric part of the unit cell. Crystals have been successfully transferred to an artificial mother liquor, pH = 7.8, 20 mM in Mg(2+) and 5 mM in 2-phospho-D-glycerate. We believe that under these lower salt concentration and more alkaline conditions we should be able to localize the two metal ions that participate in catalysis as well as examine binding of high-affinity inhibitors.

Journal Article↗

Fluoride inhibition of yeast enolase: crystal structure of the enolase-Mg(2+)-F(-)-Pi complex at 2.6 A resolution.

Enolase in the presence of its physiological cofactor Mg2+ is inhibited by fluoride and phosphate ions in a strongly cooperative manner (Nowak, T, Maurer, P. Biochemistry 20:6901, 1981). The structure of the quaternary complex yeast enolase-Mg(2+)-F(-)-Pi has been determined by X-ray diffraction and refined to an R = 16.9% for those data with F/sigma (F) > or = 3 to 2.6 A resolution with a good geometry of the model. The movable loops of Pro-35-Ala-45, Val-153-Phe-169, and Asp-255-Asn-266 are in the closed conformation found previously in the precatalytic substrate-enzyme complex. Calculations of molecular electrostatic potential show that this conformation stabilizes binding of negatively charged ligands at the Mg2+ ion more strongly than the open conformation observed in the native enolase. This closed conformation is complementary to the transition state, which also has a negatively charged ion, hydroxide, at Mg2+. The synergism of inhibition by F- and Pi most probably is due to the requirement of Pi for the closed conformation. It is possible that other Mg(2+)-dependent enzymes that have OH- ions bound to the metal ion in the transition state also will be inhibited by fluoride ions.

Fluorides↗

[Application of ultrafiltration during cardiopulmonary bypass].

The ultrafiltration (UF) was employed in 20 patients undergoing open-heart operation with cardiopulmonary bypass (CPB). The number of controls was 10. The average UF duration was 24.7 +/- 9.6 min (12-49) and the average amount of ultrafiltrate was 1433.5 +/- 482.6 ml (650-2,350 ml). The volume load of UF group was similar with that of the control group. The output volume of UF group was greater than that of the control group (P less than 0.01). After UF, the degree of increase in hematocrit, plasma albumin and total plasma protein was 33.8%, 34.7%, and 26.0%, respectively. Moreover, we did not find any abnormal increase in blood viscosity. No additional adverse actions of UF were found.

Adolescent↗