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Q Han

Publications and source records attributed to Q Han.

70 records · Page 4Linked to original sources
PubMed1996

The second space experiment of protein crystallization with domestic facilities.

The second experiment of protein crystallization was performed on domestic re-entry satellite FSW-2 in 1994-07. The results are superior to the ones of the first mission in 1992: 9 of 10 different proteins were crystallized in space, and 70% of the total 48 samples yielded single crystals. Besides hen egg-white lysozyme which grew high-quality crystals on the first mission, an acidic phospholipase A2(aPLA2) from snake venom and hemoglobin from Anser Indicus produced good-quality crystals suitable for X-ray diffraction analyses. The positive effect of microgravity on protein crystal growth is verified again at this time.

Aerospace Medicine↗
PubMed1994

A cross-reactive idiotope on T cells from PL/J mice and Lewis rats that recognizes different myelin basic protein encephalitogenic epitopes but is restricted by TCR V beta 8.2.

Encephalitogenic T cells of both PL/J mice and Lewis rats are restricted by TCR V beta 8.2, although they recognize different epitopes in the myelin basic protein (MBP) molecule. We sought the presence of a cross-reactive idiotope (Id) in encephalitogenic T cells of Lewis rats by examining the effects of mAb F30 anti-Id, which recognized a TCR Id in PL/J T cells, on the encephalitogenic LR88L1 cell line derived from Lewis rats and specific for guinea pig MBP peptide 68-88. The LR88L1 cells were I-A restricted and TCR V beta 8.2+, and their proliferation and secretion of IL-2 and TNF-alpha induced by guinea pig MBP peptide 68-88 was inhibited by mAb F30 anti-Id. As shown by FACS analysis and by immunoprecipitation of TCR from radiolabeled LR88L1 cell lysates, the F30 anti-Id bound to the TCRs of V beta 8.2+ LR88L1 cells. In addition, TCR sequences in the F30+ population of LR88L1 cells were the same as those of encephalitogenic Lewis rat T cells published previously. The F30+ LR88L1 cells showed reduced encephalitogenicity compared with F30- or unsorted LR88L1 cells. The mechanism for this reduction by anti-Id probably resulted from the induction of anergy, in that IL-2 reversed the anti-Id effect. The control LR99L1 T cell line, also encephalitogenic, but specific for MBP peptide 87-99 and I-E, and not TCR V beta 8.2 restricted, failed to react with, or have its cytokine secretion inhibited by, mAb F30 anti-Id. These results demonstrate an interspecies cross-reactive Id expressed in common by encephalitogenic T cells that share a similar TCR, although they differ in MBP epitope specificity. These findings suggest that a common Id restricted by TCR, but less restricted by the encephalitogenic epitope, and recognized by the Id-bearing autoreactive T cells may represent an immunotherapeutic approach for treating autoimmune demyelinating diseases.

Amino Acid Sequence↗
PubMed1994

Comparison of properties of murine monoclonal anti-idiotypic antibodies generated with idiotype-bearing monoclonal antibodies to myelin basic protein peptides or their complementary peptides.

The present study was undertaken to compare the features of monoclonal antibody (mAb) anti-idiotope (Id) induced by complementary peptides, synthesized on the basis of inverted hydropathy for a myelin basic protein (MBP) peptide, or by conventional methodology using Id-bearing antibodies to the same MBP peptide as immunogen. The six reagents studied consisted of mAbs reactive with MBP peptide acetyl 1-9 and MBP peptide 80-89 and anti-Id reagents against these two mAbs prepared by either the complementary peptide or the conventional approach. ELISA, immunoblotting, immunoinhibition of hybridoma cell production of Id-bearing mAb to MBP, and FACS indicated that the anti-Ids generated by either technique were similar although existing in a range reflecting biologic phenomena. mAbs anti-Id prepared by either method continued to show an IgM isotype preference, possibly related to technical considerations, and continued to recognize a cross-reactive Id on the kappa light chain of the mAbs to MBP peptides acetyl 1-9 and 80-89. There was no indication that the anti-Ids prepared by the complementary peptide approach were restrictive or selective in a manner different from those made by the conventional approach.

Amino Acid Sequence↗
PubMed1994

Monoclonal antibodies to a TCR idiotope modulate the superantigen-induced responses of encephalitogenic rat T cells.

Superantigens, such as staphylococcal enterotoxins, activate T lymphocytes by linking MHC class II molecules on antigen presenting cells to the V beta element of the TCR. Through this effect on T cells, superantigens may influence the immune response and autoimmune disease. In fact, superantigens may activate or anergize cells involved in the production of experimental allergic encephalomyelitis. Lewis rats recognize an encephalitogenic epitope in myelin basic protein (MBP) residues 68-88 through an MHC class II I-A restricted process using TCR V beta 8.2. The F30 murine mAb reacts with an encephalitogenic idiotope (Id) on the TCR of V beta 8.2+ encephalitogenic Lewis rat T cells. In the present study it was demonstrated that the same mAb anti-Id inhibited the proliferation and IL-2 secretion induced by staphylococcal enterotoxins A, B and E in a V beta 8.2+ encephalitogenic Lewis rat T cell line specific for guinea pig MBP peptide 68-88. The mAb anti-Id did not inhibit the response of control T cells similarly derived but inhibited V beta 8.2- and recognizing MBP peptide 87-99. Control anti-Id failed to inhibit the response of either cell line. These findings imply that the specific antigen and superantigen react with TCR in a manner similar enough to be inhibited by the same anti-Id. The mechanism may involve the induction of anergy by the anti-Id, interference/steric hindrance by the reaction of anti-Id with TCR and possibly a little direct reaction of anti-Id with superantigens. Anti-Id directed immunotherapy may have a role in modulating the damage of inflammatory demyelination induced by both specific antigens and superantigens.

Amino Acid Sequence↗
PubMed1994

Protein crystallization in space.

The microgravity environment of space is an ideal place to study the complicated protein crystallization process and to grow good-quality protein crystals. A series of crystal growth experiments of 10 different proteins was carried out in space on a Chinese re-entry satellite FSW-2 in August, 1992. The experiments were performed for about two weeks at a temperature of 18.5 +/- 0.5 degrees C using a tube-like crystallization apparatus made in the Shanghai Institute of Technical Physics, Academia Sinica. More than half of 48 samples from 6 proteins produced crystals, and the effects of microgravity on protein crystal growth were observed, especially for hen-egg white lysozyme and an acidic phospholipase A2 from the venom of Agkistrodon halys Pallas. Analyses of the crystallization of these two enzymes in this mission showed that the microgravity environment in space may be beneficial to improve size, external perfection, morphology, internal order, and nucleation of protein crystals. Some of these positive microgravity effects were also demonstrated by the growth of protein crystals in gelled solution with the above two enzymes. A structural analysis of the tetragonal lysozyme crystal grown in space is in progress.

Ancrod↗
PubMed1994

[Pathological and ultrastructural changes in conjunctival malignant melanoma treated by cryotherapy].

The liquid nitrogen cryotherapy was used to treat conjunctival malignant melanoma. Light and transmission electron microscopic examinations were carried out before, during and after the treatment. It was discovered that the tumor cells died within a few minutes after the cryoapplication. Under transmission electron microscope, marked necrosis of tumor cells was seen 10-14 days after the treatment and a large amount of collagenous fibers and fibroblast hyperplasia were seen in the tumor in 3-4 weeks following the application, while the tumor cells were seldom found. Under light microscope, as significant necrosis of the malignant melanoma occurred, the surface conjunctival epithelium gradually grew and covered the defect of the conjunctiva, showing that the malignant melanoma cells are much more sensitive to the cryoapplication than the normal conjunctival epithelial cells.

Adult↗
PubMed1994

Protein crystal growth in microgravity.

Protein crystal growth is quite important for the determination of protein structures which are essential to the understanding of life at molecular level as well as to the development of molecular biotechnology. The microgravity environment of space is an ideal place to study the complicated protein crystallization and to grow good-quality protein crystals. A number of crystal-growth experiments of 10 different proteins were carried out in August, 1992 on the Chinese re-entry satellite FSW-2 in space using a tube crystallization equipment made in China. A total of 25 samples from 6 proteins produced crystals, and the effects of microgravity on protein crystal growth were observed, especially for an acidic phospholipase A2 and henegg-white lysozyme which gave better crystals in space than earth-grown crystals in ground control experiments. The results have shown that the microgravity in space favors the improvement of the size, perfection, morphology and internal order of the grown protein crystals.

Crystallization↗
PubMed1994

Effects of kappa-selenocarrageenan on membrane fluidity and ghost reseal ability of rat erythrocyte.

Effects of kappa-selenocarrageenan (kappa-SeC) on membrane fluidity and ghost reseal ability of rat erythrocyte were studied by measuring the fluorescence polarization and the NADH-cytochrome C oxido-reductase, respectively. After rats were given ig kappa-SeC 140 mg.kg-1.d-1 x 30 d, the fluorescence polarization was decreased in comparison with saline control group (P < 0.05). It suggested that kappa-SeC increased the membrane fluidity. The reseal ability of erythrocyte membrane (ghost) was also elevated after ig kappa-SeC 140 and 70 mg.kg-1.d-1 x 30 d (P < 0.05).

Animals↗
PubMed1993

[Pharmacokinetics of epostane in rats].

After rats were given (ig) epostane 50, 100 and 200 mg.kg-1, plasma concentrations of epostane were determined by HPLC. According to concentration versus time data, the pharmacokinetic model of epostane in all rats followed a pattern of one-compartment model. The pharmacokinetic parameters of the three doses were found to be as follows: Ka were 0.578 h-1, 0.553 h-1 and 0.439 h-1; K were 0.308 h-1, 0.282 h-1 and 0.224 h-1; T1/2 were 2.27 h, 2.54 h, 3.12 h and AUC were 786.89 micrograms.h.ml-1, 1644.43 micrograms.h.ml-1, and 3335.35 micrograms.h-1.ml-1 respectively. The tissue distribution of epostane in rats were as follows: highest in adrenal, liver, gastrointestinal tract, uterus and ovary; next in kidney, heart, brain, lung and spleen. The peak concentration times were about 3 h and comparable to plasma peak time. Plasma protein binding of epostane was determined by equilibrant dialysis of the plasma of rats given the drug and found that the degree of binding was not correlated with drug dosage under our experimental conditions. Little epostane was found in the bile, urine and feces. It appears that epostane might have undergone extensive biotransformation in the rat body.

Androstenols↗
PubMed1993

Effects of (-)-stepholidine and tetrahydroberberine on high potassium-evoked contraction and calcium influx in rat artery.

The relaxant effects of (-)-stepholidine ((-)-SPD) and tetrahydroberberine (THB) on rat aorta were studied in vitro. (-)-SPD IC50 18.1 (95% confidence limits 11.1-29.5) mumol.L-1 and THB IC50 18.6 (95% confidence limits 9.2-37.9) mumol.L-1 inhibited the contractions caused by KCl (100 mmol.L-1) concentration-dependently. Both (-)-SPD and THB markedly inhibited the 160 mmol.L-1 KCl-stimulated 45Ca influx. The inhibitions by (-)-SPD 10 mumol.L-1 and 100 mumol.L-1 were 18 +/- 13% (P > 0.05) and 47.0 +/- 2.8% (P < 0.01), respectively. The inhibitions by THB 10 mumol.L-1 and 100 mumol.L-1 were 36 +/- 9% (P < 0.01) and 43 +/- 8% (P < 0.05), respectively. The results showed that the effective concentrations of the 2 drugs inhibiting high KCl-induced contraction and 45Ca transmembrane influx in rat thoracic aorta were at a similar level, and that they were nearly 1/100 and 1/10 of those of verapamil respectively, indicating that (-)-SPD and THB had similar calcium channel blocking effect on rat artery, but were weaker than verapamil.

Animals↗
PubMed1992

Chimeras of hepatic lipase and lipoprotein lipase. Domain localization of enzyme-specific properties.

Chimeric molecules between human lipoprotein lipase (LPL) and rat hepatic lipase (HL) were used to identify structural elements responsible for functional differences. Based on the close sequence homology with pancreatic lipase, both LPL and HL are believed to have a two-domain structure composed of an amino-terminal (NH2-terminal) domain containing the catalytic Ser-His-Asp triad and a smaller carboxyl-terminal (COOH-terminal) domain. Experiments with chimeric lipases containing the HL NH2-terminal domain and the LPL COOH-terminal domain (HL/LPL) or the reverse chimera (LPL/HL) showed that the NH2-terminal domain is responsible for the catalytic efficiency (Vmax/Km) of these enzymes. Furthermore, it was demonstrated that the stimulation of LPL activity by apolipoprotein C-II and the inhibition of activity by 1 M NaCl originate in structural features within the NH2-terminal domain. HL and LPL bind to vascular endothelium, presumably by interaction with cell surface heparan sulfate proteoglycans. However, the two enzymes differ significantly in their heparin affinity. Experiments with the chimeric lipases indicated that heparin binding avidity was primarily associated with the COOH-terminal domain. Specifically, both HL and the LPL/HL chimera were eluted from immobilized heparin by 0.75 M NaCl, whereas 1.1 M NaCl was required to elute LPL and the HL/LPL chimera. Finally, HL is more active than LPL in the hydrolysis of phospholipid substrates. However, the ratio of phospholipase to neutral lipase activity in both chimeric lipases was enhanced by the presence of the heterologous COOH-terminal domain, demonstrating that this domain strongly influences substrate specificity. The NH2-terminal domain thus controls the kinetic parameters of these lipases, whereas the COOH-terminal domain modulates substrate specificity and heparin binding.

Amino Acid Sequence↗
PubMed1992

[Antiarrhythmic effects of kappa-seleno-carrageenan in experimental animals].

The effect of Kappa-seleno-carrageenan, an organic compound containing selenium, on aconitine, BaCl2 and ouabain-induced arrhythmias were studied. When rats were given ip 9 mg.kg-1.d-1 x 5 d or ig single dose of 35, 70, 140 mg.kg-1, the threshold dose of aconitine was elevated significantly to induce HA. The effect seems to resemble that of ip Na2SeO3 1 mg.kg-1 x d-1 x 5 d. With increasing ig dose, the threshold dose of aconitine was elevated for inducing VE, VT, VF. When ip 9 mg.kg-1 x d-1 x 5 d or ig 70 mg.kg-1 was given, the threshold doses of BaCl2 in inducing VF (in rats) and ouabain in inducing VE (in guinea-pig) were elevated. However, no influence was observed for ip Na2SeO3 1 mg.kg-1 x d-1 x 5 d.

Aconitine↗
PubMed1983

Serum high density lipoprotein cholesterol and factors influencing its level in healthy Chinese.

Serum HDL-cholesterol (HDLc) levels were studied on 2399 healthy urban inhabitants, from newborn to 78 years of age, in Shanghai. The results were as follows. (1) Frequency distribution of serum HDLc levels in most groups was approximately normal after age 20. (2) The serum HDLc levels and HDLc/total cholesterol ratio varied with age and sex among healthy subjects. The mean values of HDLc for people over 30 years of age were 58.7 +/- 11.2 mg/100 ml for males and 62.5 +/- 12.2 mg/100 ml for females. The difference was of statistical significance (P less than 0.01). (3) The mean values of serum HDLc were found to be 40.9 +/- 6.0 mg/100 ml and 40.7 +/- 7.9 mg/100 in male and female neonates respectively. These figures are quite similar to those reported from Western countries and Japan. The serum HDLc level rose steadily with age and such elevation was more marked in females than males before age 30. However, the values became closer at age 60, then began to decrease in both sexes. (4) Serum HDLc levels varied markedly with body weight; they correlated negatively with the weight/height index. (5) No statistically significant relationship was found in Chinese between smoking or drinking and serum HDLc levels. The high level of HDLc seemed a result of environmental factors and is, possibly, related to the lower incidence of coronary heart disease in China.

Adolescent↗
PubMedDate not supplied

3D-structure of human estrogenic 17beta-HSD1: binding with various steroids.

Human estrogenic dehydrogenase (17beta-HSD1) catalyses the last step in the biosynthesis of the active estrogens that stimulate the proliferation of breast cancer cells. While the primary substrate for the enzyme is estrone, the enzyme has some activity for the non-estrogenic substrates. To better understand the structure function relationships of 17beta-HSD1 and to provide a better ground for the design of inhibitors, we have determined the crystal structures of 17beta-HSD1 in complex with different steroids. The structure of the complex of estradiol with the enzyme determined previously (Azzi et al., Nature Structural Biology 3, 665-668) showed that the narrow active site was highly complementary to the substrate. The substrate specificity is due to a combination of hydrogen bonding and hydrophobic interactions between the steroid and the enzyme binding pocket. We have now determined structures of 17beta-HSD1 in complex with dihydrotestosterone and 20alpha-OH-progesterone. In the case of the C19 androgen, several residues within the enzyme active site make some small adjustments to accommodate the increased bulk of the substrate. In addition, the C19 steroids bind in a slightly different position from estradiol with shifts in positions of up to 1.4 A. The altered binding position avoids unfavorable steric interactions between Leu 149 and the C19 methyl group (Han et al., unpublished). The known kinetic parameters for these substrates can be rationalized in light of the structures presented. These results give evidence for the structural basis of steroid recognition by 17beta-HSD1 and throw light on the design of new inhibitors for this pivotal steroid enzyme.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Recombinant methioninase infusion reduces the biochemical endpoint of serum methionine with minimal toxicity in high-stage cancer patients.

The tumor-specific increased minimal requirement for methionine has been shown to be a highly promising therapeutic target. To attack this target we have previously cloned the methioninase gene from Pseudomonas putida and produced recombinant methioninase (rMETase). A pilot Phase I clinical trial has been carried out to determine rMETase toxicity, rMETase pharmacokinetics, and serum MET-depletion in cancer patients. Patients with advanced breast cancer, lung cancer, renal cancer and lymphoma were given a single rMETase treatment at doses ranging from 5,000 to 20,000 units by i.v. infusion over 6-24 hours. No clinical toxicity was observed in any patient after rMETase treatment. rMETase levels reached 0.1 to 0.4 units per ml of serum in the patients which correspond to therapeutic levels in vitro. The lowest serum methionine levels in rMETase-treated patients were 0.1% of the pre-treatment levels corresponding to approximately 0.1 microM, which also correlates to therapeutic levels in vitro. The results of the rMETase pilot Phase I clinical trial therefore indicate that i.v. infusion of rMETase is safe and effectively depletes its biochemical target of serum methionine suggesting potential efficacy in future clinical trials.

Antimetabolites, Antineoplastic↗