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Biomedical subjects

D W Zhang

Publications and source records attributed to D W Zhang.

At least 19 recordsLinked to original sources
PubMed2004

Fractionation of peptide with disulfide bond for quantum mechanical calculation of interaction energy with molecules.

We present a computational study of a recently developed molecular fractionation with conjugated caps (MFCC) method for application to peptide/protein that has disulfide bonds. Specifically, we employ the MFCC approach to generate peptide fragments in which a disulfide bond is cut and a pair of conjugated caps are inserted. The method is tested on two peptides interacting with a water molecule. The first is a dipeptide consisting of two cysteines (Cys-Cys) connected by a disulfide bond and the second is a seven amino acid peptide consisting of Gly-Cys-Gly-Gly-Gly-Cys-Gly with a disulfide cross link. One-dimensional peptide-water potential curves are computed using the MFCC method at various ab initio levels for a number of interaction geometries. The calculated interaction energies are found to be in excellent agreement with the results obtained from the corresponding full system ab initio calculations for both peptide/water systems. The current study provides further numerical support for the accuracy of the MFCC method in full quantum mechanical calculation of protein/peptide that contains disulfide bonds.

Binding Sites↗
PubMed2003

Molecular caps for full quantum mechanical computation of peptide-water interaction energy.

We present a systematic study of numerical accuracy of various forms of molecular caps that are employed in a recently developed molecular fractionation scheme for full quantum mechanical computation of protein-molecule interaction energy. A previously studied pentapeptide (Gly-Ser-Ala-Asp-Val) or P5 interacting with a water molecule is used as a benchmark system for numerical testing. One-dimensional potential energy curves are generated for a number of peptide-water interaction pathways. Our study shows that various forms of caps all give consistently accurate energies compared to the corresponding full system calculation with only small deviations. We also tested the accuracy of cutting peptide backbone at different positions and comparisons of results are presented.

Algorithms↗
PubMed2003

Entangled double-helix phase.

We present a novel phase with an entangled double-helix structure. Beams with this phase have the same transverse patterns as those of interference between two doughnut beams. This proposed method allows a complete set of the superpositions of the doughnut modes or the orbital angular momentum states with different topological orders to be obtained. Furthermore, it introduces a simple continuous and controlled rotation of the transverse patterns by use of a spatial light modulator. It can be used to form a three-dimensional structure by three-dimensional trapping in an optical tweezers setup or to study the quantum characteristics of an optical vortex.

Journal Article↗
PubMed2003

Optical doughnut for optical tweezers.

We describe novel optical doughnuts for optical tweezers. With new phase functions, the proposed doughnut beams have dark cores in specified shapes. The technique can offer a simple method for creating a variety of beam shapes to match the trapped objects. One can rotate the beams directly by revolving their phase structures about their axes on the initial plane. The technique for generating the traditional Laguerre-Gaussian beam can be used to create these novel beams.

Journal Article↗
PubMed2001

Identification of a nonconserved amino acid residue in multidrug resistance protein 1 important for determining substrate specificity: evidence for functional interaction between transmembrane helices 14 and 17.

Murine multidrug resistance protein 1 (mrp1), differs from its human ortholog (MRP1) in that it fails to confer anthracycline resistance and transports the MRP1 substrate, 17beta-estradiol 17-(beta-d-glucuronide) (E(2)17betaG), very poorly. By mutating variant residues in mrp1 to those present in MRP1, we identified Glu(1089) of MRP1 as being critical for anthracycline resistance. However, Glu(1089) mutations had no effect on E(2)17betaG transport. We have now identified a nonconserved amino acid within the highly conserved COOH-proximal transmembrane helix of MRP1/mrp1 that is important for transport of the conjugated estrogen. Converting Ala(1239) in mrp1 to Thr, as in the corresponding position (1242) in MRP1, increased E(2)17betaG transport 3-fold. Any mutation of mrp1 Ala(1239), including substitution with Thr, decreased resistance to vincristine and VP-16 without altering anthracycline resistance. However, introduction of a second murine to human mutation, Q1086E, which alone selectively increases anthracycline resistance, into mrp1A1239T restored resistance to both vincristine and VP-16. To confirm the importance of MRP1 Thr(1242) for E(2)17betaG transport and drug resistance, we mutated this residue to Ala, Cys, Ser, Leu, and Lys. These mutations decreased E(2)17betaG transport 2-fold. Conversion to Asp eliminated transport of the estrogen conjugate and also decreased leukotriene C(4) transport approximately 2-fold. The mutations also reduced the ability of MRP1 to confer resistance to all drugs tested. As with mrp1, introduction of a second mutation based on the murine sequence to create MRP1E1089Q/T1242A restored resistance to vincristine and VP-16, but not anthracyclines, without affecting transport of leukotriene C(4) and E(2)17betaG. These results demonstrate the important role of Thr(1242) for E(2)17betaG transport. They also reveal a highly specific functional relationship between nonconserved amino acids in TM helices 14 and 17 of both mrp1 and MRP1 that enables both proteins to confer similar levels of resistance to vincristine and VP-16.

ATP-Binding Cassette Transporters↗
PubMed2001

Identification of an amino acid residue in multidrug resistance protein 1 critical for conferring resistance to anthracyclines.

Murine multidrug resistance protein 1 (mrp1), unlike human MRP1, does not confer resistance to anthracyclines. Previously, we have shown that a human/murine hybrid protein containing amino acids 959-1187 of MRP1 can confer resistance to these drugs. We have now examined the functional characteristics of mutant proteins in which we have converted individual amino acids in the comparable region of mrp1 to those present at the respective locations in MRP1. These mutations had no effect on the drug resistance profile conferred by mrp1 with the exception of converting glutamine 1086 to glutamate, as it is in the corresponding position (1089) in MRP1. This mutation created a protein that conferred resistance to doxorubicin without affecting vincristine resistance, or the ability of mrp1 to transport leukotriene C(4) (LTC(4)) and 17beta-estradiol 17-(beta-d-glucuronide) (E(2)17betaG). Furthermore, mutation Q1086D conferred the same phenotype as mutation Q1086E while the mutation Q1086N did not detectably alter the drug resistance profile of mrp1, suggesting that an anionic side chain was required for anthracycline resistance. To confirm the importance of MRP1 E1089 for conferring resistance to anthracyclines, we mutated this residue to Gln, Asp, Ala, Leu, and Lys in the human protein. The mutation E1089D showed the same phenotype as MRP1, while the E1089Q substitution markedly decreased resistance to anthracyclines without affecting LTC(4) and E(2)17betaG transport. Conversion of Glu-1089 to Asn, Ala, or Leu had a similar effect on resistance to anthracyclines, while conversion to a positive amino acid, Lys, completely eliminated resistance to anthracyclines and vincristine without affecting transport of LTC(4), E(2)17betaG, and the GSH-dependent substrate, estrone-3-sulfate. These results demonstrate that an acidic amino acid residue at position 1089 in predicted TM14 of MRP1 is critical for the ability of the protein to confer drug resistance particularly to the anthracyclines, but is not essential for its ability to transport conjugated organic anions such as LTC(4) and E(2)17betaG.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial.

PURPOSE: To study the value of postoperative radiotherapy for non-small-cell lung cancer (NSCLC) with positive regional lymph metastases (NI or N2) after radical surgery. MATERIALS AND METHODS: From February 1982 to October 1995, 366 patients with NSCLC and N1 or N2 disease were randomized into postoperative radiotherapy (S + R) (183 patients) and no further treatment (S alone) (182 patients). Postoperative radiotherapy (RT) was administrated 3-4 weeks after radical operation. Irradiated fields covered the bronchial stump, ipsilateral hilum, and most of the mediastinum. The midplane dose was 6000 cGy/30 fractions/6 weeks, with the spinal cord limited to 4000 cGy/20 fractions/4 weeks or less. One hundred thirty-four patients in S + R group and 162 patients in S alone group were evaluated. Clinical data were comparable in both arms, except for the numbers of N2 patients. RESULTS: The 3-year and 5-year overall survival rates were 51.9% and 42.9% in the S + R group and 50.2% and 40.5% in the S alone Group (p = 0.56). The 3-year and 5-year disease-free survival rates were 50.7% +/- 4.7% and 42.9% +/- 5.2% in the S + R group vs. 44.4% +/- 4.3% and 38.2% +/- 4.5% in the S alone group (p = 0.28), respectively. In the patients with NI or T3-4 tumors, there was a trend toward improved survival in the S + R group, especially in the patients with T3-4N1M0. These patients demonstrated 20% improvement in overall survival (p = 0.092) and greater than 20% better disease-free survival (p = 0.057). Postoperative RT reduced local recurrence but had no impact on distant metastases. CONCLUSION: Postoperative RT significantly reduced local relapses, but did not improve overall survival, due to a high frequency of distant metastases in this patient group.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

Alkaloid-fullerene systems through photocycloaddition reactions.

The photocycloaddition of tertiary amines to ¿60fullerene (C(60)) is an interesting and useful reaction. We wished to extend the applications of this type of reaction through an investigation of the photoaddition of alkaloids to C(60) for the purpose of synthesizing novel and complex photoadducts that are difficult to obtain by usual methods. Irradiation of tazettine (2) or gramine (3) with C(60) in toluene leads to formation of one monoadduct (6 or 7), whereas scandine (1a) or 10-hydroxyscandine (1b) reacts with C(60) photochemically to give two products, the expected ¿6,6 monoadduct (5a, 5b) and a new type of monoadduct with a bis-¿6, 6 closed structure (4a, 4b). These new structures were characterized by UV-vis, FT-IR, (1)H NMR, (13)C NMR, (1)H-(1)H COSY, ROESY, HMQC (heteronuclear multiple-quantum coherence), and HMBC (heteronuclear multiple-bond connectivity) spectroscopy. The techniques of time-of-flight secondary ion MS (TOF-SIMS) and field desorption MS (FD-MS) were used for the mass determination. (3)He NMR analysis of the product mixture from photoaddition of 1a to C(60) containing a (3)He atom ((3)He@C(60)) led to two peaks at -9.091 and -11.090 ppm relative to gaseous (3)He, consistent with formation of a ¿6, 6-closed monoadduct and a bis-¿6,6 closed adduct. Presumably, the bis-¿6, 6 closed adducts are formed by an intramolecular ¿2 + 2 cycloaddition of the vinyl group to the adjacent 6,6-ring junction of C(60) after the initial photocycloaddition.

Alkaloids↗
PubMed2000

[Studies on the distribution of actin during meiotic prophase I of Nicotiana rustica L].

The Pollen Mother Cells of Nicotiana Rustica L. were studied using the techniques of immunofluorescence microscopy and protein A-colloidal gold IEM. Immunofluorescence microscopy indicates the presence of actin in both nuclei and cytoplasm. IEM observation shows that gold particles are present in cytoplasm, chromatin and cytomictic channels. These results indicate that actin has some relation with chromatin condensing at synizesis. Moreover, actin may also play an important role in cytomixis.

Actins↗
PubMed1998

Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (AGC)--report on 370 patients.

PURPOSE: An attempt was made to define the role of radiotherapy before operation for AGC. METHODS AND MATERIALS: From January 1978 to May 1989, a prospective randomized trial on preoperative radiotherapy (R+S) vs. surgery alone (S) for AGC was carried out in 370 patients. Patients were randomized into a combined group (R+S, 171 patients) or a surgery alone group (S, 199 patients) by the envelope method. 8-MV photon or telecobalt was used for the preoperative radiation therapy, using anterior-posterior opposing parallel fields to deliver 40 Gy to the cardia, lower segment of the esophagus, fundus, lesser curvature, and hepatogastric ligament. Surgery was performed after 2 to 4 weeks rest. RESULTS: The 5- and 10-year survival rates of the R+S Group and the S Alone Group were 30.10% and 19.75%, 20.26% and 13.30%, respectively. The survival curves of these two groups diverged right from the beginning after the operation over the ninth year. Statistics by Kaplan-Meier log rank test proves that the difference is significant (chi2 = 6.74, p = 0.0094). The immediate results were: resection rate 89.5% and 79.4% (p < 0.01); pathologic stage after resection T2 12.9% and 4.5% (p < 0.01), T4 40.3% and 51.3% (p < 0.05), lymph node metastasis rates 64.3% and 84.9% (p < 0.001); operative mortality rates 0.6% and 2.5%; intrathoracic leak rates 1.8% and 4.0%, respectively. The causes of failure were: local uncontrol and recurrence 38.6% vs. 51.7% (p < 0.025), regional lymph node metastasis 38.6% vs. 54.6% (p < 0.005), distant metastasis 24.3% vs. 24.7%. CONCLUSION: Preoperative radiation therapy is able to improve the results of surgery for adenocarcinoma of the gastric cardia.

Adenocarcinoma↗
PubMed1995

Alternative splicing of ED-A and ED-B sequences of fibronectin pre-mRNA differs in chondrocytes from different cartilaginous tissues and can be modulated by biological factors.

The alternative splicing of the ED-A and ED-B segments of fibronectin pre-mRNA was examined in epiphyseal, costal, and meniscal cartilage from 3-week-old beagles and in nasal, tracheal, articular, and meniscal cartilage from 1- and 2-year-old Labrador retrievers. In contrast to the 100% expression of ED-B(+) mRNA that has been reported for embryonic chick cartilage (Bennett, V.D., Pallante, K.M., and Adams, S.K. (1991) J. Biol. Chem. 266, 5918-5924), all cartilages studied expressed both the ED-B(+) and ED-B(-) forms of fibronectin mRNA with the exception of the trachea, in which expression was 100% ED-B(-). Of all cartilages studied, only the meniscus had detectable levels of ED-A(+) mRNA. Placing articular cartilage chondrocytes in primary monolayer culture dramatically up-regulated the expression of ED-A(+) mRNA to 25% of the total, and this expression was further increased by the addition of transforming growth factor beta 1 or fucoidan to the culture medium. The expression of ED-B(+) mRNA remained at about 18% in the cultured chondrocytes and was not further affected by either transforming growth factor beta 1 or fucoidan. In contrast, dibutyryl cyclic adenosine monophosphate decreased the relative expression of both the ED-A(+) and ED-B(+) forms of fibronectin pre-mRNA. We concluded that the expression of ED-B(+) fibronectin remains relatively high in chondrocytes from cartilaginous canine tissues (15-35%) with the exception of the trachea, in contrast to the less than 10% expression of ED-B(+) fibronectin reported for other non-fetal tissues.

Alternative Splicing↗
PubMed1995

Accumulation of fibronectin in articular cartilage explants cultured with TGF beta 1 and fucoidan.

Fibronectin is a glycoprotein involved in cell matrix interactions. In osteoarthritis, fibronectin levels in the lesion cartilage are elevated up to 20-fold above control levels. In these experiments, explants of disease-free cartilage cultured in the presence of a combination of TGF beta 1 and the sulfated fucopolysaccharide, fucoidan, accumulated fibronectin at levels comparable to those found in osteoarthritic lesions. TGF beta 1 increased fibronectin synthesis, most of which was released to the medium. The addition of fucoidan favored retention of the newly synthesized fibronectin within the matrix. The fibronectin which accumulated as a result of these treatments was similar to the fibronectin in normal and osteoarthritic cartilage with respect to the ED-B+ alternative splice form. No change in the proteoglycan content of the cartilage explants with elevated fibronectin levels was detected.

Animals↗
PubMed1995

Prospective multimodality treatment of SCLC--experience during the past 18 years.

Lung cancer has been one of the leading malignancies in China. Since 1989 it has ranked first among common malignancies in the male population, and second in females. In 1975, a multimodality treatment study group for lung cancer was organized in our institute. The group has since expanded to 15 institutions in the Beijing and Tianjin area during the past four years. The present communication is based on our experiences and data, and tries to explain the treatment strategy of our study group.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Regulation of human protein C gene expression by the mouse WAP promoter.

A 4.1 kb mouse whey acidic protein (mWAP) promoter was cloned from a C57BL/6 cosmid library. The tissue-specific and developmental pattern of expression of a hybrid gene comprised of the mWAP promoter fragment and the human protein C (HPC) gene was analysed in transgenic mice. The corresponding RNA was detected mainly in the mammary gland, with 'leakage' of expression in the salivary gland and kidney. The developmental pattern of transgene expression differed from that of the endogenous WAP gene. In particular, recombinant HPC (rHPC) transcripts were detected earlier in pregnancy than WAP RNA, with no significant increase during lactation. This indicates that regulatory elements responsible for developmental regulation are located outside the 4.1 kb mWAP gene promoter fragment, or if present, may be subject to position effects. Precocious expression of the transgene did not compromise the health or nursing abilities of transgenic females. Expression of rHPC affected the appearance of the mammary alveoli and alveolar epithelial cells in lactating transgenic mice. The alveoli were less distended and alveolar epithelial cells appeared cuboidal with centrally positioned nuclei. We suggest that the inefficient intracellular processing of rHPC can alter the histological appearance of alveolar epithelial cells in the transgenic mammary gland.

Animals↗
PubMed1994

Inefficient processing of human protein C in the mouse mammary gland.

Vitamin K-dependent plasma protein, human Protein C (HPC) has been expressed in transgenic mice, using a 4.2 kb mouse whey acidic protein (WAP) promoter, 9.0 kb HPC gene and 0.4 kb 3' flanking sequences. Expression was mammary gland-specific and the recombinant human Protein C (rHPC) was detected in milk at concentrations of 0.1 to 0.7 mg ml-1. SDS-PAGE revealed that the single, heavy and light chains of rHPC migrated with increased electrophoretic mobility, as compared to HPC. Enzymatic deglycosylation showed that these molecular weight disparities are in part due to differential glycosylation. The substantial increase observed in the amount of single chain protein, as well as the presence of the propeptide attached to 20-30% of rHPC, suggest that mouse mammary epithelial cells are not capable of efficient proteolytic processing of rHPC. The Km of purified rHPC for the S-2366 synthetic substrate was similar to that of plasma-derived HPC, while the specific activity was about 42-77%. Amino acid sequence analyses and low anticoagulant activity of purified rHPC suggest that gamma-carboxylation of rHPC is insufficient. These results show that proteolytic processing and gamma-carboxylation can be limiting events in the overexpression of fully biologically active rHPC in the mouse mammary gland.

Amino Acid Sequence↗
PubMed1994

Billings natural family planning in Shanghai, China.

With cervical mucus, or Billings, method of family planning, a woman learns to recognize the characteristics of her cervical mucus that identify the fertile phase in her menstrual cycle. She and her partner abstain from sexual activity during a period from the first indication of mucus until four days after the mucus peak day, which includes ovulation. They also abstain during menses, because mucus can be confused with menstrual bleeding. This method of family planning is used widely, worldwide, by couples seeking a natural, reliable method of family planning. Between July 1988 and May 1990, 688 couples of child-bearing age, most of whom were parous, used the Billings method for contraception. Five hundred and fifty of these couples used the method for more than 12 months. Efficacy, continuation rates, and discontinuation rates were analyzed using life-table analysis for 10,175 woman-months of data collected. The net cumulative discontinuation rates per 100 women at 12 and 18 months were 19.85 and 34.58, respectively, resulting in continuation rates of 80.15 and 65.42. The discontinuation rates per 100 women for method-related reasons at 12 and 18 months were 1.61 and 2.84, respectively, while the discontinuation rates for unintended pregnancy were 1.02 and 1.18. During the study, 67 subjects volunteered to have vaginal smears taken from the upper part of the vaginal wall for cytologic examinations, and among them serum and urine LH levels were measured in 10 subjects and urinary estrogen and progesterone were assayed in 35 cases. These tests related other indications of the menstrual cycle to the ability of the women to judge ovulation by cervical mucus. Our research suggests that further investigation of the Billings method is warranted and that careful planning and organization are needed to disseminate the method more broadly.

Cervix Mucus↗