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Biomedical subjects

H Qian

Publications and source records attributed to H Qian.

At least 109 records · Page 6Linked to original sources
PubMed1998

Terminal twist induced continuous writhe of a circular rod with intrinsic curvature.

It is well known that a large linking number induces an abrupt writhing of a circular rod with zero intrinsic curvature, i.e., the stress-free state of the rod is straight. We show here that for any rod with a uniform natural curvature, no matter how small the intrinsic curvature is, a twist will induce a continuous writhing from the circular configuration and the abrupt writhing is only the limiting case when the intrinsic curvature is absolutely zero. The implication of this result on elastic models of circular DNA is discussed.

DNA↗
PubMed1998

Analysis of the assembly function of the human immunodeficiency virus type 1 gag protein nucleocapsid domain.

Previous studies have shown that in addition to its function in specific RNA encapsidation, the human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC) is required for efficient virus particle assembly. However, the mechanism by which NC facilitates the assembly process is not clearly established. Formally, NC could act by constraining the Pr559gag polyprotein into an assembly-competent conformation or by masking residues which block the assembly process. Alternatively, the capacity of NC to bind RNA or make interprotein contacts might affect particle assembly. To examine its role in the assembly process, we replaced the NC domain in Pr55gag with polypeptide domains of known function, and the chimeric proteins were analyzed for their abilities to direct the release of virus-like particles. Our results indicate that NC does not mask inhibitory domains and does not act passively, by simply providing a stable folded monomeric structure. However, replacement of NC by polypeptides which form interprotein contacts permitted efficient virus particle assembly and release, even when RNA was not detected in the particles. These results suggest that formation of interprotein contacts by NC is essential to the normal HIV-1 assembly process.

Animals↗
PubMed1998

Brain administration of leptin causes deletion of adipocytes by apoptosis.

Leptin, produced in adipocytes, works through the central nervous system (CNS) to modulate food intake and energy expenditure, resulting in rapid loss of body fat depots. It is now shown that this process includes adipocyte apoptosis. Adipocyte deletion by apoptosis occurred after intracerebroventricular (i.c.v.) administration of leptin in rats. Adipose tissue of leptin-treated rats demonstrated characteristic features of apoptosis, including internucleosomal fragmentation of genomic DNA, elevated levels of DNA strand breaks and a reduction in total DNA content and cellular volume. These apoptotic features were absent in control and pair-fed rats and in other tissues of leptin-treated rats.

Adipocytes↗
PubMed1998

Artificial cell containing superoxide dismutase--selection of folding aids for stabilisation of SOD.

Superoxide dismutase (abbreviated as SOD) has been vigorously studied in the fields of radical chemistry and related life science. One of practical problems is how to keep its activity in certain adverse conditions causing denaturation. Artificial cell containing SOD can be prepared by polymer encapsulation or nanocapsulation which has been found to be effective to improve the stability of SOD. For construction of an ideal artificial cell system, some folding aids or aggregation inhibitors were utilised to enhance SOD stability. In this study, three groups of biopolymers are selected as folding aids or aggregation inhibitors for stabilisation of SOD, i.e. albumin, carbohydrates and glycoproteins. Results indicate that the thermostability of SOD is affected by different sort of albumin while some carbohydrates such as cyclodextrins are found to be able to enhance SOD stability. In addition, it is firstly found that selected glycoproteins such as alpha-macroglobulin and ovalbumin are several types of effective folding aids for stabilisation of SOD. They can protect SOD against denaturation even at very high temperature(over 100 degrees C). The stability was tested by the measurement of SOD activity loss using autooxidation method in different adverse conditions such as high temperature, extreme pH medium, proteolytic hydrolysis and long shelf life storage. The possible stabilisation mechanism of using cyclodextrins and glycoproteins as folding aids were discussed.

Albumins↗
PubMed1998

Increased leptin resistance as rats grow to maturity.

Three or eight-month-old Sprague-Dawley rats were treated intracerebroventricularly (ICV) with 5 microg of rat leptin/d for 5 days to determine the effect of age on leptin's actions in ingestive behavior, adipose tissue cellularity, organ weights, body composition, and blood metabolite profile. Effects of leptin on food intake were greater in young immature rats (22.0 vs. 5.7 g/d) than in mature rats (17.4 vs. 9.3 g/d) with a leptin x age interaction (P< 0.01). Leptin results in body weight loss (P < 0.001) by 19% and 9% in young and mature rats, respectively. Water intake was reduced by leptin treatment only in young animals (P< 0.001). The decrease in carcass weight by leptin treatment (P < 0.001) was observed in both young (22%) and mature rats (9%). Leptin treatment greatly reduced retroperitoneal (0.82 vs. 0.11 g, P < 0.05) and epididymal fat weight (1.90 vs. 0.48 g, P < 0.003), associated with a reduction in total adipocyte cell number, DNA content, and cellular volume in young rats; however, there were no effects of leptin in the mature rats. In addition, young rats also displayed a 60% loss of carcass lipid content. An increase in serum fatty acid levels by leptin treatment was observed also only in young rats (P< 0.001). An interaction of leptin by age that was observed for the reduction of serum glucose levels by leptin treatment (P < 0.04) further indicated that mature rats showed a leptin insensitivity compared to young rats. In summary, the data suggest that normal rats become resistant to leptin as they age.

Adipose Tissue↗
PubMed1998

[Application of multi-tumor markers in ovarian carcinoma].

OBJECTIVE: To improve the specificity and sensitivity of diagnosis and to strengthen postoperative monitoring for patients with ovarian cancer. METHODS: Sera obtained from patients-ovarian epithelial carcinoma (67 cases), benign ovarian tumor (33 cases) and from donor (38 cases) as control. Serologic examination of 5 tumor markers--SA, LSA, CA125, CP2, and 6B11Ab2 was performed. RESULTS: The sensitivity and specificity in diagnosis of ovarian cancer were 83.6% and 85.9% respectively for CA125 alone (> 35 kU/L) whereas 86.6% and 94.4% respectively for multi-tumor markers combined in which 3 or more indices showed positive. In addition, serial measurements of multi-tumor markers have been done for 1 year after operation in 24 cases of ovarian epithelial carcinoma. The correlations between the levels of multi-tumor markers either and the results of second look operation or and clinical manifestation of recurrence were analyzed. CONCLUSION: Multi-tumor markers examination could improve the diagnosis of ovarian cancer and early detection of recurrence.

Biomarkers, Tumor↗
PubMed1998

[Expression of endothelin-1 and nitric oxide synthase mRNA in gastric mucosa of rats with cirrhosis and portal hypertensive gastropathy after disconnective operations].

OBJECTIVE: To investigate expression of endothelin-1 (ET-1) and nitric oxide synthase(NOS) gene in gastric mucosa in the rats with cirrhosis and portal hypertensive gastropathy (PHG) after disconnective operation. METHODS: Wistar rats were divided into three groups: normal (n = 12), cirrhosis and PHG (n = 12), and post-disconnective (n = 12). The rat models were induced by intraperitonal injection of thiocetamide for 16 weeks. The third group rats were reared for 3 months after the operations. ET-1 and NOS mRNA from the gastric mucosa of the three groups were measured quantitatively by Dot blot technique. RESULTS: ET-1 mRNA decreased in the PHG rats as compared to the nomal rats (P < 0.01). Further decrease was found in the post-disconnective rats (P < 0.01). NOS mRNA increased slightly in the PHG rats (P > 0.05) and increased obviously in the post-disconnective rats (P < 0.01). CONCLUSIONS: After the cirrhosis and PHG rats were subjected to disconnective operations, ET-1 was insufficient and NOS was too much in the gastric mucosa. These resulted in the gastric mucosal vessel dilatation. The imbalance of ET/NO proportion could partly attribute to rebleeding after disconnection.

Animals↗
PubMed1998

[The detection of breast carcinoma micrometastases in axillary lymph nodes by reverse transcriptase-polymerase chain reaction].

OBJECTIVE: To detect tumor micrometastases in axillary lymph nodes of breast carcinoma so as to obtain more reliable information about nodes status and its clinical significance. METHOD: The expression of CK19 mRNA was measured in 61 axillary lymph nodes (LNs) of 15 breast carcinomas by using reverse transcriptase-polymerase chain reaction (RT-PCR). RESULT: CK19 mRNA expression was detected in all 15 breast carcinomas, but not in 5 control LNs. Of 61 axillary LNs analysed by HE staining and CK19 RT-PCR, 7 LNs were found to have metastases by histological staining and CK19 RT-PCR. Of the remaining 54 axillary nodes, 12 were found to have metastases by using CK19 RT-PCR method. CONCLUSION: The CK19 RT-PCR method is more sensitive than histological study for the detection of micrometastases in LNs (P < 0.01). This new method is of value in differentiating breast cancer patients at high risk for relapse from those with negative lymph node.

Axilla↗
PubMed1998

[Diagnosis of Falciparum malaria by immunochromatographic test].

AIM: To evaluate the applicability of rapid immunochromatographic test(ICT) for diagnosing falciparum malaria in outpatient clinics in endemic area. METHODS: With thick blood smear method as control, ICT was used for the detection of P. falciparum. RESULTS: The sensitivity and specificity of ICT in detecting P. falciparum was 94.7% and 90.3%, respectively. No cross-reaction with P. vivax was found (P > 0.05). CONCLUSION: ICT is much more rapid and simple than thick blood smear method for the diagnosis of falciparum malaria, and can be applied in the outpatient clinics in endemic area.

Adolescent↗
PubMed1998

[A new method for evaluating malaria surveillance effectiveness--establishment and application of an index system].

AIM: To establish a comprehensive index system which is suitable for evaluating the effectiveness of malaria surveillance schemes. METHODS: Delphi method was used to screen the existed effectiveness evaluation indices by experts to determine key indices and weighted coefficients. RESULTS: Three indices, i.e. autochthonous incidence, ratio of cases detected (ROCD) and ratio of introduced/imported cases were selected. Their weighted coefficients were 0.36, 0.31 and 0.33, respectively. An index system named the malaria surveillance effectiveness index (MSEI) was built up and formulated as [formula: see text] which was applied to study cost-effectiveness of the two malaria surveillance schemes (A and B). According to the formula, the MSEIs in the study areas using the schemes A and B were 48.56 and 45.93, respectively. However, the cost for increasing a score of MSEI by implementing the scheme A was four times as high as that by implementing the scheme B. CONCLUSION: The MSEI is practicable for evaluating the overall effectiveness of malaria surveillance schemes, especially in the cost-effectiveness analysis and health-economic evaluation.

China↗
PubMed1998

[TLC analysis of harpagoside in devil claw extract and its tablets].

OBJECTIVE: To set up a method for TLC identification of the Devil Claw Extract and its tablets, and make a quantitative analysis of harpagoside the main active constituent in the Extract. METHOD: A characteristic TLC chromatogram was obtained by using pre-coated silica gel 60F254 plate, chloroform-ethyl acetate-methanol-water as the solvent system and 5% vanillin-sulfuric acid solution or 10% sulfuric acid-ethanol solution as the spray reagent; and quantitative analysis was carried out using silica gel plate modified by 1% sodium hydroxide, and UV absorptive scanning at 283 nm. RESULT: The regression equation is Y = 20.33X + 92.72, r = 0.9993, linear range between 16.8-151.2 ng, and average recovery 101.2%. CONCLUSION: This method has been validated by linearity, stability, sensitivity and reproducibility tests, and proved to be accordant with the requirement for quantitative analysis of the herbal medicine in question.

Chromatography, Thin Layer↗
PubMed1997

Hyperfractionated accelerated radiation therapy for non-small cell lung cancer: clinical phase I/II trial.

PURPOSE: In an attempt to improve local control and survival of nonsmall cell lung cancer (NSCLC), hyperfractionated accelerated radiation therapy (HART) was carried out as a clinical phase I/II trial. METHODS AND MATERIALS: HART was delivered by 1.1 Gy/fraction, three fractions per day with intervals of 4 h and five treatment days per week. The clinical tumors were irradiated to 74.3 Gy (72.6-75.9)/66-69 fx, 33 days (29-40) (not corrected for lung density), and the subclinical lesions, to 50.0 Gy (48.4-50.6)/44-46 fx, 33 days (29-40). Sixty-nine patients with NSCLC were enrolled in this study. Nine patients were withdrawn from the study during HART due to different reasons. Sixty patients formed the study for outcome analyses. They were 57 males and 3 females with median age of 61 years (21-77). There were 41 cases of squamous cell carcinoma, 15 cases of adenocarcinoma, and 4 cases of large cell carcinoma. Overall, favorable patients (KPS > or = 70, weight loss < 5% and Stages I, II, IIIa) accounted for 73% (44 of 60) of all patients. Forty-four patients (73%) received adjuvant chemotherapy (DDP + VP16) with median cycles of 1.8 before and/or after HART. In order to compare the outcome of HART with conventional irradiation, 50 NSCLC patients treated by conventional fractionated irradiation (CFI) during the same period were chosen as the basis to evaluate relative effects of HART. They derived from the control group of another clinical trial of hyperfractionated irradiation for NSCLC in the same department. They received median tumor dose of 63.9 Gy (62.8-65.0)/34 fx (32-36), 48 days (45-53). RESULTS: 1. Acute and late complications: (a) In HART, 87% of patients (52 cases) developed acute radiation esophagitis: Grade 1-2, 46 cases (77%) and Grade 3, 6 cases (10%), at 2.5 weeks (2-3.5 weeks) after HART began. Five patients with Grade 3 esophagitis had their HART interrupted for <7 days. In CFI, esophagitis was much less (44%,p < 0.05) with 38% of Grade 1-2 and 6% of Grade 3. (b) In HART, acute pulmonary symptoms (RTOG Grade 1-2) occurred in 17% (10 cases), and acute radiation pneumonitis (Grade 3), in 8% (5 cases), while in CFI, they were 24% and 2% (p > 0.05), respectively. Late lung fibrosis (RTOG Grade 1-2) appeared in 20% (12 cases), whereas 18% in CFI (p > 0.05). (c), No other severe acute or late complications have been observed so far in HART. 2. Immediate response. In HART, 20% of patients (12 cases) achieved CR, 60% (36 cases), PR and 20% (12 cases), NR or PD. In CFI, the above three percentages were 10, 28, and 62%, respectively (p < 0.001). 3. Follow-up. The 1-, 2-, and 3-year actuarial survivals were 72, 47, and 28% for HART, and 60, 18, and 6% for CFI, respectively (p < 0.001). Better local control was seen in HART than in CFI with 1-, 2-, and 3-year local control rates being 71, 44, 29%, and 60, 20, and 5%, respectively (p = 0.001). Distant metastases developed less in HART than in CFI. The 1-, 2-, and 3-year distant metastasis rates were 23, 36, and 50% in HART, but 30, 48, and 80% in CFI (p = 0.021). CONCLUSION: 1. HART could be tolerated by most of the favorable NSCLC patients. The predominant complication was acute esophagitis. No other severe acute or late complications have been observed so far. 2. HART resulted in better survivals and local controls, and less distant metastases than CFI.

Adenocarcinoma↗
PubMed1997

A quantitative analysis of single protein-ligand complex separation with the atomic force microscope.

Force measurements on and within single macromolecular complexes utilizing techniques such as atomic force microscopy, optical trapping, flexible glass fibers, and magnetic beads provide a rich source of quantitative data on biomolecular processes. Stochastic thermal fluctuations, an undesirable source of noise in macroscopic biochemical experiments, are an essential element of these sensitive and novel experiments. With the proper analysis, a great deal of information can be gleaned from measurements of these fluctuations. A quantitative framework for analyzing such measurements, based on Kramers' theory of molecular dissociation, is developed. The analysis reveals the kinetic origin and stochastic nature of the measurements. This framework is presented in the context of protein-ligand separation with the atomic force microscope.

Journal Article↗
PubMed1997

A simple theory of motor protein kinetics and energetics.

A simple stochastic theory for kinetics and energetics of the movement of single motor proteins is presented. The model combines the biochemical cycle of nucleotide hydrolysis with the motor protein translocation. Based on the theory of Markov processes, the model provides the force-velocity relationship, the isometric force, and the stochastic stepping of the motor protein along its one-dimensional track. The theoretical model provides a conceptual framework for realistic studies of motor proteins. Relationship between the present theory and other existing models is discussed.

Journal Article↗
PubMed1997

Thermodynamic hierarchy and local energetics of folded proteins.

The cooperativity of local fluctuations within the folded state of a protein is demonstrated based on applying the "multiple-probe principle" to the hydrogen exchange (HX) rates of a set of amide protons of the protein. A hierarchical thermodynamic analysis is presented for the protein energetics, which includes both global two-state folding-unfolding transition and local cooperative fluctuations within the folded state. The analysis dissects the local fluctuations from the global unfolding; both lead to the HX but from the folded and unfolded states, respectively. It provides the newly observed HX behavior of proteins in mild denaturant, namely solvent and temperature dependent HX rates from the folded state, with a quantitative interpretation in terms of a set of local energetic parameters. These local energetic parameters contain much information concerning the structures and stabilities of native proteins.

Amides↗
PubMed1997

Solution structure of phenol hydroxylase protein component P2 determined by NMR spectroscopy.

Phenol hydroxylase from Pseudomonas sp. CF600 is a member of a family of binuclear iron-center-containing multicomponent oxygenases, which catalyzes the conversion of phenol and some of its methyl-substituted derivatives to catechol. In addition to a reductase component which transfers electrons from NADH, optimal turnover of the hydroxylase requires P2, a protein containing 90 amino acids which is readily resolved from the other components. The three-dimensional solution structure of P2 has been solved by 3D heteronuclear NMR spectroscopy. On the basis of 1206 experimental constraints, including 1060 distance constraints obtained from NOEs, 70 phi dihedral angle constraints, 42 psi dihedral angle constraints, and 34 hydrogen bond constraints, a total of 12 converged structures were obtained. The atomic root mean square deviation for the 12 converged structure with respect to the mean coordinates is 2.48 A for the backbone atoms and 3.85 A for all the heavy atoms. This relatively large uncertainty can be ascribed to conformational flexibility and exchange. The molecular structure of P2 is composed of three helices, six antiparallel beta-strands, one beta-hairpin, and some less ordered regions. This is the first structure among the known multicomponent oxygenases. On the basis of the three-dimensional structure of P2, sequence comparisons with similar proteins from other multicomponent oxygenases suggested that all of these proteins may have a conserved structure in the core regions.

Amino Acid Sequence↗
PubMed1997

Local interactions and the optimization of protein folding.

The role of local interactions in protein folding has recently been the subject of some controversy. Here we investigate an extension of Zwanzig's simple and general model of folding in which local and nonlocal interactions are represented by functions of single and multiple conformational degrees of freedom, respectively. The kinetics and thermodynamics of folding are studied for a series of energy functions in which the energy of the native structure is fixed, but the relative contributions of local and nonlocal interactions to this energy are varied over a broad range. For funnel shaped energy landscapes, we find that 1) the rate of folding increases, but the stability of the folded state decreases, as the contribution of local interactions to the energy of the native structure increases, and 2) the amount of native structure in the unfolded state and the transition state vary considerably with the local interaction strength. Simple exponential kinetics and a well-defined free energy barrier separating folded and unfolded states are observed when nonlocal interactions make an appreciable contribution to the energy of the native structure; in such cases a transition state theory type approximation yields reasonably accurate estimates of the folding rate. Bumps in the folding funnel near the native state, which could result from desolvation effects, side chain freezing, or the breaking of nonnative contacts, significantly alter the dependence of the folding rate on the local interaction strength: the rate of folding decreases when the local interaction strength is increased beyond a certain point. A survey of the distribution of strong contacts in the protein structure database suggests that evolutionary optimization has involved both kinetics and thermodynamics: strong contacts are enriched at both very short and very long sequence separations.

Kinetics↗