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Biomedical subjects

S Xie

Publications and source records attributed to S Xie.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cloning, expression and chromosome locations of the human DNMT3 gene family.

DNA methylation plays an important role in animal development and gene regulation. In mammals, several genes encoding DNA cytosine methyltransferases have been identified. DNMT1 is constitutively expressed and is required for the maintenance of global methylation after DNA replication. In contrast, the murine Dnmt3 family genes appear to be developmentally regulated and behave like de novo DNA methyltransferases in vitro. In this study, we have cloned human DNMT3A and DNMT3B that encode full-length DNMT3A and DNMT3B proteins with 98% and 94% amino acid sequence identity to their murine homologues. The DNMT3A and DNMT3B show high homology in the carboxy terminal catalytic domain and contain a conserved cysteine-rich region, which shares homology with the X-linked ATRX gene of the SNF2/SWI family. We have mapped human DNMT3A and DNMT3B to chromosomes 2p23 and 20q11.2 respectively, and determined the DNMT3B genomic structure. We further show that DNMT3A expression is ubiquitous and can be readily detected in most adult tissues, whereas DNMT3B is expressed at very low levels in most tissues except testis, thyroid and bone marrow. Significantly, both DNMT3A and DNMT3B expression is elevated in several tumor cell lines to levels comparable to DNMT1. The cloning of the human DNMT3 genes will facilitate further biochemical and genetic studies of their functions in establishment of DNA methylation patterns, regulation of gene expression and tumorigenesis.

Amino Acid Sequence↗
PubMed1999

Orally active, hydrolytically stable, semisynthetic, antimalarial trioxanes in the artemisinin family.

In only three chemical operations, natural trioxane lactone artemisinin (1) was converted into a series of C-10 carbon-substituted 10-deoxoartemisinin compounds 4-9. The three steps involved lactone reduction, replacement of the anomeric lactol OH by F using diethylaminosulfur trifluoride, and finally boron trifluoride-promoted substitution of F by aryl, heteroaryl, and acetylide nucleophiles. All of these C-10 nonacetal, chemically robust, enantiomerically pure compounds 4-9 have high antimalarial potencies in vitro against Plasmodium falciparum malaria parasites, and furans 5a and 5b and pyrrole 7a are antimalarially potent also in vivo even when administered to rodents orally.

Administration, Oral↗
PubMed1999

Design of reactive porous polymer supports for high throughput bioreactors: poly(2-vinyl-4,4-dimethylazlactone-co-acrylamide- co-ethylene dimethacrylate) monoliths.

Enzymatic bioreactors with both high flow characteristics and mechanical stability based on macroporous poly(2-vinyl-4, 4-dimethylazlactone-co-acrylamide-co-ethylene dimethacrylate) monoliths have been prepared. Covalent immobilization of trypsin on these support is achieved in a single reaction step using the azlactone functional groups. Optimization of hydrophilic/hydrophobic properties of the monolith affords a support that does not shrink in water and leads to immobilized enzyme that shows high activity in the hydrolysis of both low and high molecular weight substrates such as L-benzoyl arginine ethyl ester and casein. The catalytic activity of the monolithic reactor is maintained even at a flow velocity of 180 cm/min, which substantially exceeds those reported in the literature for packed bed reactors.

Bioreactors↗
PubMed1999

Identification of a new aspartic proteinase expressed by the outer chorionic cell layer of the equine placenta.

The pregnancy-associated glycoproteins (PAGs) are placental antigens that were initially characterized as pregnancy markers in the maternal circulation of domestic ruminant species. They are members of the aspartic proteinase gene family, having greatest sequence identity with pepsinogens. However, some are not capable of functioning as enzymes. The PAGs are associated with a large gene family within the Artiodactyla order (cattle, camels, pigs). So far, no members of this family have been characterized in species outside this order. This report describes the cloning and initial characterization of a PAG-like protein (equine PAG or ePAG) expressed in the placenta of the horse and zebra (order Perrisodactyla). Equine PAG is a proteinase capable of degrading 14C-hemoglobin and catalyzing the removal of its own pro-peptide. The ePAG mRNA is restricted to the chorion both prior to implantation and in the term placenta. Equine PAG is secreted from cultured placental tissue as both a processed (mature) and unprocessed (zymogen) form. Equine PAG shares similar identity with the PAGs and pepsinogens and probably arose from a pepsinogen-like precursor that gained the ability to be expressed in the placenta. The promoter of the ePAG gene shares sequence identity with the promoter from a bovine PAG gene but not with promoters of other aspartic proteinases. Therefore, we hypothesize that ePAG is a remnant of the pepsinogen-like progenitor gene that was expanded within the Artiodactyla to create the large and highly diverse PAG family.

Amino Acid Sequence↗
PubMed1999

Partners in care: a model of collaboration.

It is estimated that 3 million persons in the United States have congestive heart failure. This diagnosis accounts for more than 5% of total health expenditures. A method to decrease the costs of health care was initiated through the partners-in-care model of collaborative practice. A research study exploring the use of nurse case managers in collaboration with cardiologists and primary care physicians is being conducted with persons older than 65 years. This care encompasses both inpatient and outpatient care. The intervention comprises nurse visits in the hospital and in the home as well as telephone support for 6 months after the index hospitalization. The outcomes of quality of life, functional status, mortality, morbidity, and costs are being examined. Collaborative health care partnerships may be an effective strategy to decrease health care costs and improve quality of life and functional status of older persons with congestive heart failure.

Aged↗
PubMed1999

[Study on the induction of xenogeneic tolerance of rat to mouse bone marrow transplantation].

OBJECTIVE: To establish an effective protocol for potential clinical usage in inducing donor-specific tolerance across xenogeneic barriers. METHODS: C57BL/6 (B6) mice were conditioned with 5 Gy sublethal total body irradiation (TBI), followed by infusion of 4 x 10(7) Lewis rat bone marrow cells on day 0, then were intraperitonially administered 150 mg/kg cyclophosphamide (CP) on day 2. Recipients were characterized for engraftment with xenogeneic bone marrow cells by using fluorescence activated cell sorter (FACS) to determine the percentage of rat origin cells in the peripheral blood lymphocytes(PBL), splenic and thymic lymphoid cells on day 30, 60 and 90. Mixed lymphocyte reaction (MLR) and delayed type hypersensitivity (DTH) assay were performed on day 30 to examine the tolerance status. RESULTS: Rat lymphoid chimeras were reliable present in the tolerant B6 mice for more than 3 months. B6 recipients were specifically tolerant to host xenoantigens in MLR and DTH assays, but were still immunocompetent to MHC-disparate third party BALB/c mouse or DA rat stimulator cells. CONCLUSION: A durable rat to mouse xenogeneic bone marrow transplantation tolerance was achieved in this modal.

Animals↗
PubMed1999

[Ankylosing spondylitis in Shantou: clinical experience in fifteen years].

OBJECTIVE: To evaluate the clinical features of ankylosing spondylitis (AS) in Shantou area and improve the diagnostic level and therapeutic effect. METHODS: Clinical and laboratory data, and the methods and effects of therapy were analyzed. Some patients were followed up. RESULTS: 94% of the cases had an insidious onset. Low back pain or discomfort, peripheral arthritis, positive "4" test and pressing tenderness over the sacroiliac joints and lumbar spine were the frequent symptoms and signs. The degree of sacroiliitis and involvement of hip and spine were related to the disease duration. However, hip joint involvement in juvenile onset AS did not relate to the disease duration. Some cases with disease duration as long as 16 years still remained at II of degree sacroiliitis. Clinical improvement was more obvious in the first two years of treatment. Although some patients came to a standstill condition after this period, yet the disease activity might still relapse with withdrawal of the treatment. The rate of adhering to the treatment for 1, 2, and over 5 years was 34.6%, 28.4%, and 10.3% respectively. The radiological changes frequently did not parallel with the clinical manifestations. CONCLUSION: Early diagnosis is of importance in improving the prognosis of AS and adherence to slow-acting anti-rheumatic drug therapy is beneficial in disease controlling. A follow up of more than 3 years is necessary to estimate the therapeutic efficacy, and the radiological change is the key indicator. AS is a heterogenic disease and the risk factors for prognosis should be further studied.

Adolescent↗
PubMed1999

[The analysis of manganese through electrochemical stripping ellipsometry].

This paper introducing the cathodic stripping ellipsometry with a new function Vop for analyzing manganese quantitatively. The results indicated that the related average deviation of this method are more smaller than the stripping voltamimetry of electrochemistry and providing a lot of information about electrode processes.

English Abstract↗
PubMed1998

Antimalarial cyclic peroxy ketals.

Over 20 new, cyclic, peroxy ketals have been prepared via a two-step protocol starting with readily available aryl methyl ketones. Structure-activity correlations using in vitro antimalarial data as a guide for optimization of potency have led to the design and synthesis of seven new peroxides that have IC50 values of 31-85 nM (artemisinin IC50 = 8.4 nM). Some SAR generalizations are discussed.

Animals↗
PubMed1998

Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells.

We have shown previously that de novo methylation activities persist in mouse embryonic stem (ES) cells homozygous for a null mutation of Dnmt1 that encodes the major DNA cytosine methyltransferase. In this study, we have cloned a putative mammalian DNA methyltransferase gene, termed Dnmt2 , that is homologous to pmt1 of fission yeast. Different from pmt1 in which the catalytic Pro-Pro-Cys (PPC) motif is 'mutated' to Pro-Ser-Cys, Dnmt2 contains all the conserved methyltransferase motifs, thus likely encoding a functional cytosine methyltransferase. However, baculovirus-expressed Dnmt2 protein failed to methylate DNA in vitro . To investigate whether Dnmt2 functions as a DNA methyltransferase in vivo , we inactivated the Dnmt2 gene by targeted deletion of the putative catalytic PPC motif in ES cells. We showed that endogenous virus was fully methylated in Dnmt2 -deficient mutant ES cells. Furthermore, newly integrated retrovirus DNA was methylated de novo in infected mutant ES cells as efficiently as in wild-type cells. These results indicate that Dnmt2 is not essential for global de novo or maintenance methylation of DNA in ES cells.

Amino Acid Sequence↗
PubMed1998

Synthesis and in vitro antimalarial activity of sulfone endoperoxides.

A series of 4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]+ ++nonanes, carrying a variety of substituents at position-8 (4) were prepared by a short and efficient method from R-(+)-limonene. Key reactions include thiol oxygen cooxidation, and alkylation and acylation of a sterically hindered tertiary alcohol compatible with the endoperoxy functionality. Some of compounds 4, which are structurally related to yingzhaosu A (2), were found to exhibit in vitro antimalarial activity comparable to that of artemisinin (1) and superior to that of arteflene (3).

Animals↗
PubMed1998

Orally active antimalarial 3-substituted trioxanes: new synthetic methodology and biological evaluation.

On the basis of a mechanistic understanding of the mode of action of artemisinin-like antimalarials, a series of structurally simple 3-aryl-1,2,4-trioxanes 5 was designed and was prepared in three to five operations from commercial reactants. The 3-aryl group was attached in each case as a nucleophile. In an electronically complementary fashion, 3-(fluoroalkyl)-trioxanes 6 were prepared via attachment of electrophilic fluoroalkyl esters. Both in vitro and in vivo antimalarial evaluations of these new trioxanes showed 12 beta-methoxy-3-aryltrioxanes 5g, 5j, 5k, and 51 to be highly potent, with crystalline fluorobenzyl ether trioxane 5k especially potent even when administered to rodents orally. As shown by rearrangement of hexamethyl Dewar benzene into hexamethylbenzene, iron-induced degradation of some of these 3-aryltrioxanes 5 involves generation of high-valent iron oxo species that might kill malaria parasites.

Administration, Oral↗
PubMed1998

An aspartic proteinase expressed in the equine placenta.

This manuscript describes the cloning of a novel aspartic proteinase expressed in the placenta of the horse (order Perrisodactyla). Evidence for similar genes in the cat (Carnivora) and ruminants (Artiodactyla), indicates that these molecules have been conserved within widely divergent species with distinct types of placentation. Since ePAG is produced by the outer cell layer (trophoblast) of the placenta, it can tentatively be grouped with the pregnancy-associated glycoproteins (PAG) of cattle, sheep, and pig. The high sequence identity that ePAG shares with pepsinogens as well as the PAG, indicates that ePAG may be the evolutionary bridge that links these two groups of aspartic proteinases.

Animals↗
PubMed1998

Expression of steroidogenic acute regulatory protein messenger ribonucleic acid is limited to theca of healthy bovine follicles collected during recruitment, selection, and dominance of follicles of the first follicular wave.

Expression of mRNA encoding steroidogenic acute regulatory protein (StAR) in bovine follicles during recruitment and selection was examined. Dairy heifers (4-5/time period) were ovariectomized at 12, 24, 36, 48, 60, 72, 84, or 96 h after initiation of the first follicular wave (Time 0) after estrus. Follicles were collected and stored at -80 degrees C until sectioning. Expression of StAR mRNA was localized by in situ hybridization and quantified by image analysis. Expression of StAR mRNA was first detected in theca interna of antral follicles as small as 0.5 mm in diameter and increased with increasing follicular size (>/= 4 mm; r = 0.75; p < 0.001). StAR mRNA was undetectable in granulosa of healthy follicles at any size or stage of follicular wave examined. However, granulosa or luteinized granulosa of some advanced or late atretic follicles expressed StAR mRNA. During recruitment, StAR mRNA expression in theca cells was similar among recruited follicles (4-8 mm). During selection of dominant follicles (36-48 h), StAR mRNA was expressed in theca of more than one follicle (7-9 mm); therefore, expression of StAR mRNA may not be associated with dominant follicle selection. StAR mRNA in theca was higher (p < 0.05) at 48 h after initiation of the first follicular wave than at 12, 24, and 36 h, and it remained elevated thereafter through 96 h. Dominant follicles expressed more (p < 0.01) StAR mRNA in theca than did subordinate healthy follicles. Healthy follicles expressed higher (p < 0.05) StAR mRNA in theca than atretic follicles. In summary, levels of StAR mRNA increased in theca with stage of follicular wave and size of follicles. Follicular atresia was associated with reduced expression of StAR mRNA in theca cells. The results indicate that expression of StAR mRNA in theca may not be the primary limiting factor for follicular recruitment and selection.

Animals↗
PubMed1998

Pepsin-related molecules secreted by trophoblast.

The pregnancy-associated glycoproteins (PAGs) were first described as placental antigens of cattle that were also present in the blood serum of the mother after implantation. Molecular cloning studies have shown that they are members of the aspartic proteinase gene family and closely related to the pepsinogens. An enzymatic role seems unlikely, as at least some of them have mutations likely to render them enzymatically inactive. Nevertheless, these molecules have retained the substrate-binding cleft of the pepsins and are expressed abundantly in trophectoderm, particularly in the invasive binucleate cell component. There may be as many as 100 PAG genes in cattle and sheep, many of which are transcribed. PAGs are also products of the placenta of the pig, a species whose progenitors diverged from the ruminants at least 55 million years ago. There is even evidence for PAG-like molecules outside the Artiodactyla. Although their function remains elusive, it seems unlikely that these placentally expressed molecules are simply oddities in view of their long-term evolutionary survival and conspicuous presence at the fetal-maternal interface.

Animals↗
PubMed1998

Targeted diagnosis and treatment of superficial bladder cancer with monoclonal antibody BDI-1.

OBJECTIVE: To explore the application of monoclonal antibody (McAb) to targeted treatment of bladder carcinoma through a series of in vitro and in vivo studies carried out in animal model and patients with bladder carcinoma. METHODS: Monoclonal antibody BDI-1 against bladder carcinoma was prepared by the lymphocyte hybridoma technique. McAb was conjugated with 99mTc by direct reduction method. Momodin (MD) was covalently linked to McAb by SPDP method. Radioimmunoimaging of nude mice xenografts and patients with bladder carcinoma were performed with BDI-1-99mTc conjugates. An immunotoxin (BDI-1-MD) was inducted via a catheter into the bladder. Targeted treatment with BDI-1-MD was carried out in 18 patients. RESULTS: This study showed the specificity of McAb, and clear imaging of nude mice bearing xenografts. Distribution analysis of 99mTc-BDI-1 in nude mice showed the highest value of T/NT in bladder tumor. Targeted diagnosis and treatment for patients by intravesical administration are very safe and effective. CONCLUSION: The bladder cancer seems an ideal model for diagnostic and therapeutic approaches using regional administration of McAb conjugates via a catheter direct into the bladder.

Animals↗