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Biomedical subjects

S Zhang

Publications and source records attributed to S Zhang.

At least 109 records · Page 6Linked to original sources
PubMed2001

The shorter zinc finger protein ZNF230 gene message is transcribed in fertile male testes and may be related to human spermatogenesis.

The zinc finger gene family represents one of the largest in the mammalian genome, with several of these genes reported to be involved in spermatogenesis. A newly discovered gene has been identified that is expressed abundantly in the testicular tissue of fertile men as determined by mRNA differential display. The gene encodes a C(3)HC(4)-type zinc finger protein motif (ring finger motif) consistent with a role in pre-meiotic or post-meiotic sperm development. The gene was named ZNF230 and mapped to the short arm of chromosome 11 (11p15). ZNF230 has two transcripts, of 1 kb and 4.4 kb in length. The shorter 1 kb transcript was only detected in testicular tissue whereas the longer 4.4 kb transcript was not detected in testis but was found in several other tissues. The lack of detectable ZNF230 expression in azoospermic patients by reverse transcriptase-mediated PCR analysis is interpreted to mean that this gene is involved in maintaining normal human male fertility.

Amino Acid Sequence↗
PubMed2001

Regioselective synthesis of polysubstituted pyrazoles and isoxazoles.

A regioselective synthesis has been developed for the preparation of unsymmetrical 1,3,5-triaryl-4-alkylpyrazolines and -pyrazoles by treatment of alpha-benzotriazolyl-alpha,beta-unsaturated ketones with monosubstituted hydrazines followed by alkylation at the 4-position of the pyrazoline ring. Reaction of alpha-benzotriazolyl-alpha,beta-unsaturated ketones with hydroxylamine gives 3,5-disubstituted isoxazoles regioselectively.

Crystallography, X-Ray↗
PubMed2001

Msh2 DNA mismatch repair gene deficiency and the food-borne mutagen 2-amino-1-methy1-6-phenolimidazo [4,5-b] pyridine (PhIP) synergistically affect mutagenesis in mouse colon.

Msh2 deficiency and food-borne carcinogen PhIP have been implicated as genetic and environmental factors, respectively, in human colon carcinogenesis. It is not clear whether loss of one or both alleles of Msh2 gene increases the mutational sensitivity in colon when exposed to environmental carcinogens. In the current study, Msh2(+/-)/lacI and Msh2(-/-)/lacI double transgenic mice were treated with PhIP and mutations in the lacI gene were studied in the colon. The spontaneous mutation frequency (MF) is approximately eightfold higher in Msh2(-/-) mice than in Msh2(+/+) mice, while Msh2(+/-) mice display similar levels of spontaneous mutation as the Msh2 wild type mice. PhIP induced a significant increase in MF in all genotypes of mice. However, induced MF is much higher in Msh2(-/-) mice compared to Msh2(+/+) and Msh2(+/-) mice. Msh2(+/-) mice displayed an increased level of G:C>T:A transversions and -1 frameshifts upon PhIP treatment. In contrast, loss of both Msh2 alleles mainly results in increased frequency of G:C>A:T transitions when exposed to PhIP. These results suggest that a defect in mismatch repair may result in an enhanced sensitivity from exposure to a dietary carcinogen. It also provides insight into interaction between genetic and environmental factors in human carcinogenesis.

Animals↗
PubMed2001

Regiospecific synthesis of 4-(2-oxoalkyl)pyridines.

[reaction: see text]. A new and operationally simple method has been developed for the regiospecific syntheses of 4-(2-oxoalkyl)pyridines from ketones and pyridine in good yields, using triflic anhydride to activate the pyridine ring.

Journal Article↗
PubMed2001

Structure-activity relationship studies of a bisbenzimidazole-based, Zn(2+)-dependent inhibitor of HCV NS3 serine protease.

A survey of isosteric replacements of the phosphonoalanine side chain coupled with a process of conformational constraint of a bisbenzimidazole-based, Zn(2+)-dependent inhibitor of hepatitis C virus (HCV) NS3 serine protease resulted in the identification of novel series of active compounds with extended side chains. However, Zn(2+)-dependent HCV NS3 inhibition was relatively insensitive to the structural variations examined but dependent on the presence of negatively charged functionality. This result was interpreted in the context of an initial electrostatic interaction between protease and inhibitor that is subsequently consolidated by Zn(2+), with binding facilitated by the featureless active site and proximal regions of the HCV NS3 protein.

Antiviral Agents↗
PubMed2001

1H and (17)O NMR detection of a lanthanide-bound water molecule at ambient temperatures in pure water as solvent.

Lanthanide complexes of a tetra-amide derivative of DOTA (structure 4 in text) with four extended carboxymethyl esters have been characterized by X-ray crystallography and multinuclear NMR spectroscopy. [Eu(4)(H(2)O)](triflate)(3) crystallized from water in the monoclinic, P(21/)(c) space group (a = 10.366 A, b = 22.504 A, c = 23.975 A, and beta = 97.05 degrees ). The Eu(3+) cation is bound to four macrocyclic nitrogen atoms (mean Eu-N = 2.627 A) and four amide oxygen atoms (mean Eu-O(amide) = 2.335 A) in a square antiprismatic geometry with a twist angle of 38.5 degrees between the N4 and O4 planes. A single bound water molecule (Eu-O(W) = 2.414 A) occupies a typical monocapped position on the O4 surface. In pure water, resonances corresponding to a single Eu(3+)-bound water molecule were observed in the (1)H (53 ppm) and (17)O (-897 ppm) NMR spectra of [Eu(4)(H(2)O)](triflate)(3) at 25 degrees C. A fit of the temperature-dependent Eu(3+)-bound (1)H and (17)O water resonance line widths in acetonitrile-d(3) (containing 4% v/v (17)O enriched water) gave identical lifetimes (tau(m)(298)) of 789 +/- 50 micros (in water as solvent; a line shape analysis of the Eu(3+)-bound water resonance gave a tau(m)(298) = 382 +/- 5 micros). Slow water exchange was also evidenced by the water proton relaxivity of Gd(4) (R(1) = 2.2 mM(-1) s(-1), a value characteristic of pure outer-sphere relaxation at 25 degrees C). With increasing temperature, the inner-sphere contribution gradually increased due to accelerated chemical exchange between bound water and bulk water protons. A fitting of the relaxation data (T(1)) to standard SBM theory gave a water proton lifetime (tau(m)(298)) of 159 micros, somewhat shorter than the value determined by high-resolution (1)H and (17)O NMR of Eu(4). Exchange of the bound water protons in Gd(4) with bulk water protons was catalyzed by addition of exogenous phosphate at 25 degrees C (R(1) increased to 10.0 mM(-1) s(-1) in the presence of 1500-fold excess HPO(4)(2-)).

Magnetic Resonance Spectroscopy↗
PubMed2001

Drug-polyionic block copolymer interactions for micelle formation: physicochemical characterisation.

While covalent attachment of small drug molecules to AB copolymers for the formation of polymeric micelles for drug delivery has been investigated, few studies have focused on non-covalent interactions. The aim of this study was therefore to explore the potential of non-covalent interactions between an AB copolymer, Poly(aspartic acid)-poly(ethylene glycol) (Pasp-PEG), with anionic pendant groups and diminazene aceturate, a small molecular weight cationic drug. Micelles were prepared by mixing solutions of Pasp-PEG and diminazene in 25 mM Tris-HCl buffer. At all Pasp-PEG concentrations studied, the micelles appeared to be water soluble with a unimodal size distribution and ranged in size from approximately 22 to 60 nm. The polyionic micelles also displayed similar and small absolute zeta potential values at various drug:monomer molar ratios which confirmed stabilisation by the PEG corona. The scattering intensity was maximal and remained unchanged, while particle size increased slightly at pH range from 3.4 to 7.2. At this pH range both the polymer and drug would be ionised and ionic interactions possible to drive micellar formation. An increase in size and scattering intensity with addition of NaCl to the micelles was attributed to dehydration of the PEG corona which may have led to aggregation of the micelles. The absence of micellar dissociation upon addition of salt was attributed to the dominance of hydrogen bonding between Pasp and diminazene aceturate, as assessed by isothermal titration microcalorimetry. Morphological evaluation of these constructs showed them to be discrete and fairly uniform in size and shape. This study was therefore successful in confirming the potential of non-covalent interactions using an AB copolymer to form polyionic micelles for drug delivery.

Drug Delivery Systems↗
PubMed2001

[Effect of complement 4 genetic polymorphism on complement activation during cardiopulmonary bypass in open heart surgery among children].

OBJECTIVE: To evaluate the relation between complement 4 genetic polymorphism and complement activation during extracorporeal circulation in open heart surgery among children. METHODS: One hundred and fifty-six children to undergo open heart surgery with cardiopulmonary bypass in Wuhan and surrounding areas were investigated. Blood samples were obtained before the operation to analyze the C4 phenotypes by crossed immunoelectrophoresis. Before the initiation of CPB, at the end of CPB, and 10 minutes after protamine infusion, arterial blood samples were drawn to test the C4a and C3a with radioimmunoassay and lung compliance was recorded. RESULTS: The frequencies of C4 genetic phenotypes AABB, AOBB, OOBB, AABO, and AAOO were 51.28%, 17.95%, 4.49%, and 19.80% respectively among the investigated children. At the end of CPB, The C4a levels remained almost the same, and C3a levels increased significantly. Ten minutes after the protamine infusion, significant increase was seen in the levels of both C4a and C3a, especially in the OOBB phenotype group followed by AOBB phenotype group. The lung compliance began to decrease by the end of CPB, most significantly in the OOBB phenotype group, followed by the AOBB group, along with the increase of C4a level. CONCLUSION: The complement system is activated by the alternative pathway during CPB and by the classic way during the formation of protamine-heparin complexes. The complement system is activated and the lung function is damaged the most seriously during CPB among the persons with OOBB phenotype. The frequency of OOBB phenotype is higher among Chinese than among Caucasians.

Cardiac Surgical Procedures↗
PubMed2001

Molecular evidence for the independent origin of extra-ovarian papillary serous tumors of low malignant potential.

BACKGROUND: Molecular data suggest that peritoneal tumors in women with advanced-stage ovarian papillary serous adenocarcinoma are monoclonal in origin. Whether the same is true for ovarian tumors of low malignant potential is not known. We compared peritoneal and ovarian tumors from women with advanced-stage ovarian papillary serous tumors of low malignant potential to determine whether the peritoneal tumors arose from the same clone as the ovarian tumors. METHODS: We studied the clonality of 73 peritoneal and ovarian tumors from 18 women with advanced-stage ovarian papillary serous tumors of low malignant potential. Formalin-fixed, paraffin-embedded tumors and representative normal tissues were sectioned and stained with hematoxylin-eosin, representative sections from separate tumors were manually microdissected, genomic DNA was extracted from the microdissected tumors, and the polymerase chain reaction was used to amplify a CAG polymorphic site in the human androgen receptor locus on the X chromosome to determine the inactivation pattern of the X chromosome and the clonality of the tumors. RESULTS: The pattern of X-chromosome inactivation could be determined from the tumors of 13 of 18 patients. Of the 13 patients, seven (54%) had nonrandom inactivation of the X chromosome, and six of the seven had different inactivation patterns in the peritoneal and ovarian tumors. Three of these patients also had different patterns of nonrandom X-chromosome inactivation in tumors from each ovary. The remaining six patients had random patterns of X-chromosome inactivation in the peritoneal and ovarian tumors. CONCLUSIONS: Our data suggest that peritoneal and ovarian tumors of low malignant potential arise independently.

Adenocarcinoma, Papillary↗
PubMed2001

Detection of respiratory enzyme activity in Giardia cysts and Cryptosporidium oocysts using redox dyes and immunofluorescence techniques.

The fluorescent redox dye 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), combined with fluorescein-labeled antibodies, was tested for the simultaneous detection of the respiratory electron transport system (ETS) activity and enumeration of Giardia cysts and Cryptosporidium oocysts by spectral microfluorometry and epifluorescence microscopy. The reduction of CTC and p-iodonitrotetrazolium violet (INT), a non-fluorescent redox dye, was compared with propidium iodide (PI) and fluorescein diacetate (FDA) for the measurements of Giardia cyst viability over time. According to the PI and FDA staining techniques, nearly 60% of the cysts tested viable at the beginning of the observations; after 21 days their viability decreased to 5%. The redox dyes indicated that approximately 4-10% of the cysts were metabolically active 48 h after they were shed, followed by a decline in enzyme activity to near undetectable levels after 4 days. Spectral analysis on individual cysts indicated that the fluorescence emission of the reduced CTC and the fluorescein-labeled antibodies is distinctive for each compound and suitable for their simultaneous determination by microphotometry, flow cytometry and epifluorescence microscopy. The fluorescence signal remained without alteration when the cysts were transferred onto microscope slides coated with an optical embedding medium and stored at -20 degrees C. The fluorescence intensity of the reduced CTC, when properly standardized, can provide quantitative measurements of ETS activity of the cysts. This is the first report of a method to determine enzyme redox activity on intact cysts applicable to water, laboratory and animal samples.

Animals↗
PubMed2001

Quantitative similarity-based association tests using population samples.

Although genetic association studies using unrelated individuals may be subject to bias caused by population stratification, alternative methods that are robust to population stratification, such as family-based association designs, may be less powerful. Furthermore, it is often more feasible and less expensive to collect unrelated individuals. Recently, several statistical methods have been proposed for case-control association tests in a structured population; these methods may be robust to population stratification. In the present study, we propose a quantitative similarity-based association test (QSAT) to identify association between a candidate marker and a quantitative trait of interest, through use of unrelated individuals. For the QSAT, we first determine whether two individuals are from the same subpopulation or from different subpopulations, using genotype data at a set of independent markers. We then perform an association test between the candidate marker and the quantitative trait, through incorporation of such information. Simulation results based on either coalescent models or empirical population genetics data show that the QSAT has a correct type I error rate in the presence of population stratification and that the power of the QSAT is higher than that of family-based association designs.

Computer Simulation↗
PubMed2001

Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial.

PURPOSE: Preclinical studies have demonstrated that the adenovirus type 5 E1A gene is associated with antitumor activities by transcriptional repression of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of E1A gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a phase I clinical trial. PATIENTS AND METHODS: An E1A gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patients with advanced cancer of the breast (n = 6) or ovary (n = 12). RESULTS: E1A gene expression in tumor cells was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression was accompanied by HER-2/neu downregulation, increased apoptosis, and reduced proliferation. The most common treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at the injection sites. CONCLUSION: These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the E1A gene.

Adenovirus E1A Proteins↗
PubMed2001

GroEL-assisted dehydrogenase folding mediated by coenzyme is ATP-independent.

It has been commonly accepted that GroEL functions as a chaperone by modulation of its affinity for folding intermediates through binding and hydrolysis of ATP. However, we have found that NAD, as a coenzyme of d-glyceraldehyde-3-phosphate dehydrogenase (GAPDH), also stimulates the discharge of GAPDH folding intermediate from its stable complex with GroEL formed in the absence of ATP and assists refolding with the same yield as ATP/Mg(2+) does. The reactivation further increases when ATP is also present, but addition of Mg(2+) has no more effect. NADP, a coenzyme of glucose-6-phosphate dehydrogenase, also releases its folding intermediates from GroEL and increases reactivation. Different from ATP, NAD triggers the release of GAPDH intermediates bound by GroEL via binding with GAPDH itself but not with GroEL, and the released intermediates all folded to native molecules without the formation of aggregation. The collaborative effects of coenzyme and GroEL mediate GroEL-assisted dehydrogenase folding in an ATP-independent way.

Adenosine Triphosphate↗
PubMed2001

Effects of macromolecular crowding on the refolding of glucose- 6-phosphate dehydrogenase and protein disulfide isomerase.

The effects of polysaccharide, polyethylene glycol, and protein-crowding agents on the refolding of glucose-6-phosphate dehydrogenase (G6PDH) and protein disulfide isomerase have been examined. By increasing concentration during refolding, the reactivation yields of the two proteins decrease with the formation of soluble aggregates. In the presence of high concentrations of crowding agents the reactivation yields remain constant but with decreased refolding rates. The refolding of G6PDH changes from monophasic to biphasic first-order reactions in the presence of crowding agents, and the amplitude of the new slow phase increases with increasing concentrations of crowding agents. The molecular chaperone GroEL reverses the refolding kinetics of G6PDH from biphase back to monophase and accelerates the refolding process. Our results display the complexity and diversity of the effects of macromolecular crowding on both the thermodynamics and kinetics of protein folding.

Chaperonin 60↗
PubMed2001

Importance of DNA repair in carcinogenesis: evidence from transgenic and gene targeting studies.

We have generated transgenic mice by introducing copies of the E. coli O6-methylguanine-DNA methyltransferase gene, ada. Liver extracts from homozygotes demonstrate about three times the control enzyme activity and increase up to about eight-fold can be induced by treatment with zinc, since the metal-responsive metallothionein promoter is attached to the ada gene. Furthermore, studies of liver carcinogenesis in our transgenic mice demonstrated significantly reduced rates of development of hepatocellular tumors after treatment with dimethylnitrosamine or diethylnitrosamine. It is well known that xeroderma pigmentosum (XP) patients are deficient in DNA repair. The availability of XPA (XP group A complementing) knockout mice has enabled us to investigate the functional role of the XPA nucleotide excision repair gene in carcinogenesis in vivo, first using the mouse skin as a model system. XPA-/- mice demonstrated skin ulcers 5-7 days after 7,12-dimethylbenz[a]anthracene (DMBA) treatment and papilloma development within 4 weeks prior to promotion, skin tumor incidence being also much higher than in heterozygous and wild-type mice. Experiments targeting the lung, liver and tongue have also been conducted to answer the question of whether the internal organs of these mice are also susceptible to chemical carcinogens. For lung carcinogenesis, mice were instilled intratracheally with a small dose of benzo[a]pyrene. The pulmonary tumor incidence in XPA-/- mice was significantly higher than in XPA+/- and XPA+/+ mice. XPA-/- mice were also found to be have enhanced sensitivity to aflatoxin B1 regarding liver tumor induction. In addition, administration of 4-nitroquinoline-1-oxide in drinking water for 50 weeks resulted in tongue tumors only in XPA-/- mice. These studies, thus, provided convincing evidence that XPA mice are also sensitive to carcinogenesis in organs other than the skin.

Animals↗
PubMed2001

Honeybee dances communicate distances measured by optic flow.

In honeybees, employed foragers recruit unemployed hive mates to food sources by dances from which a human observer can read the distance and direction of the food source. When foragers collect food in a short, narrow tunnel, they dance as if the food source were much farther away. Dancers gauge distance by retinal image flow on the way to their destination. Their visually driven odometer misreads distance because the close tunnel walls increase optic flow. We examined how hive mates interpret these dances. Here we show that recruited bees search outside in the direction of the tunnel at exaggerated distances and not inside the tunnel where the foragers come from. Thus, dances must convey information about the direction of the food source and the total amount of image motion en route to the food source, but they do not convey information about absolute distances. We also found that perceived distances on various outdoor routes from the same hive could be considerably different. Navigational errors are avoided as recruits and dancers tend to fly in the same direction. Reported racial differences in honeybee dances could have arisen merely from differences in the environments in which these bees flew.

Animal Communication↗