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Biomedical subjects

A Wang

Publications and source records attributed to A Wang.

At least 163 records · Page 9Linked to original sources
PubMed1997

Exclusion of BMP6 as a candidate gene for cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant, generalized skeletal dysplasia in humans that has been mapped to the short arm of chromosome 6. We report linkage of a CCD mutation to 6p21 in a large family and exclude the bone morphogenetic protein 6 gene (BMP6) as a candidate for the disease by cytogenetic localization and genetic recombination. CCD was linked with a maximal two-point LOD score of 7.22 with marker D6S452 at theta = 0. One relative with a recombination between D6S451 and D6S459 and another individual with a recombination between D6S465 and CCD places the mutation within a 7 cM region between D6S451 and D6S465 at 6p21. A phage P1 genomic clone spanning most of the BMP6 gene hybridized to chromosome 6 in band region p23-p24 using FISH analysis, placing this gene cytogenetically more distal than the region of linkage for CCD. We derived a new polymorphic marker from this same P1 clone and found recombinations between the marker and CCD in this family. The results confirm the map position of CCD on 6p21, further refine the CCD genetic interval by identifying a recombination between D6S451 and D6S459, and exclude BMP6 as a candidate gene.

Bone Morphogenetic Protein 6↗
PubMed1997

Molecular cloning of cDNA for guinea pig CYP1A2 comparison with guinea pig CYP1A1.

Guinea pig CYP1A2 cDNA was isolated by RT-PCR from liver tissue of 3,3'-methylcholanthrene-treated guinea pigs. It shares considerable sequence identity with guinea pig CYP1A1 (nt 77%, aa 65%), but differs in levels of constitutive expression, function, and inducibility. Western blot analysis of protein expressed by full-length cDNA in COS-1 cells identified CYP1A2 (56 kDa) and CYP1A1 (53 kDa) proteins in corun liver microsomes. CYP1A2 transfectants metabolized methoxyresorufin and ethoxyresorufin, while CYP1A1 transfectants metabolized only ethoxyresorufin. Constitutive expression of CYP1A2 mRNA (2.0 kb) and protein was much lower than that of CYP1A1 mRNA (2.6 kb) and protein, but the fold induction of CYP1A2 by 3,3'-methylcholanthrene was greater than that of CYP1A1. Changes in splicing of CYP1A2 pre-mRNA occur upon treatment with 3,3'-methylcholanthrene.

Amino Acid Sequence↗
PubMed1997

A naturally occurring protective system in urea-rich cells: mechanism of osmolyte protection of proteins against urea denaturation.

Trimethylamine N-oxide (TMAO) is a solute concentrated in the urea-rich cells of elasmobranchs and coelacanth to offset the damaging effects of urea on intracellular protein structure and function. On the basis of transfer free energy measurements, favorable interaction of TMAO with amino acid side chains promote protein denaturation. This effect is more than offset by highly unfavorable TMAO-peptide backbone interactions that not only oppose denaturation but also provide stabilization against denaturation by urea. By combining transfer free energies of side chains and backbone with surface area exposure in the native and unfolded states of ribonuclease T1, the transfer free energies of native and unfolded protein from water to 1 M TMAO are estimated as 1.7 and 5.9 kcal/mol, respectively. These estimates agree favorably with the respective values of 1.2 and 5.4 kcal/mol determined experimentally by Lin and Timasheff [(1994) Biochemistry 33, 12695-12701]. The unfavorable transfer free energies of native and unfolded protein from water to TMAO provides a molecular level rationale for preferential hydration of proteins by osmolytes. Promotion of denaturation by urea is found to be offset by TMAO in a manner that is roughly additive of the combined effects of both solutes. The favorable interaction of urea with the backbone provides the dominant driving force for protein unfolding by this denaturant, and the unfavorable interaction of TMAO with backbone is the dominant force opposing urea denaturation. In solutions that contain significant organic solute concentration, the ascendance of the role of the peptide backbone over that of side chains can explain many observed effects in protein denaturation and stability induced by a variety of stabilizing and destabilizing organic solutes.

Amino Acids↗
PubMed1997

Effects of retinoid X receptor-selective ligands on proliferation of prostate cancer cells.

BACKGROUND: Management of prostate cancer that either is detectable by prostate specific antigen (PSA) measurements after curative intent or has spread outside of its capsule is a serious problem. Innovative, nontoxic approaches to the disease are required. One approach might be therapy with retinoids. Retinoid activities are mediated by two distinct families of transcription factors: the retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which can induce transcriptional activation through specific DNA sites or by inhibiting the transcription factor AP-1 that usually mediates cellular proliferative signals. The RARs require heterodimerization with RXRs. RXRs can form either heterodimers or homodimers; and the latter can bind to DNA response elements that are distinct from those bound by the RAR/RXR heterodimers. METHODS: A series of novel synthetic retinoids that selectively interact with RXR/RXR homodimers or RAR/RXR heterodimers, or that selectively inhibit AP-1 activity without activating transcription were evaluated for their ability to inhibit clonal growth of three human prostate cancer cell lines (PC-3, DU-145, and LNCaP). RESULTS: Several notable findings were: 1) RXR-selective retinoids, such as SR11246, were able to inhibit the clonal growth of prostate cancer cells. In contrast, SR11246 had little effect on clonal growth of myeloid leukemic cells. 2) RAR-selective retinoids also inhibited clonal growth of prostate cancer cells. 3) The retinoid (SR11238) with potent anti-AP-1 activity had no effect on the clonal growth of prostate cancer cells. CONCLUSIONS: This study shows that both RXR- and RAR-selective retinoids are worthy of further study and may be candidates for future clinical trials in prostate cancer.

Antineoplastic Agents↗
PubMed1997

Cloning, expression, and catalytic mechanism of murine lysophospholipase I.

A lysophospholipase (LysoPLA I) has been purified and characterized from the mouse macrophage-like P388D1 cell line (Zhang, Y. Y, and Dennis, E. A. (1988) J. Biol. Chem. 263, 9965-9972). This enzyme has now been sequenced, cloned, and expressed in Escherichia coli cells. The enzyme contains 230 amino acid residues with a calculated molecular mass of 24.7 kDa. It has a high helical content in its predicated secondary structure, which is also indicated in its CD spectrum. The cloned LysoPLA I was purified to homogeneity from the transformed E. coli cells by a gel filtration column and an ion exchange column. The specific activity of the purified protein is 1. 47 micromol/min.mg toward 1-palmitoyl-sn-glycero-3-phosphorylcholine at pH 8.0 and 40 degrees C, corresponding to the reported value of 1.3-1.7 micromol/min.mg for the protein purified from the P388D1 cells. In addition, the cloned protein cross-reacted with an antibody raised against LysoPLA I also purified from the P388D1 cells. The deduced LysoPLA I sequence contains a well conserved GXSXG motif found in the active site of many serine enzymes, and the activity of the LysoPLA I was irreversibly inhibited by the classical serine protease inhibitor diisopropyl fluorophosphate. Furthermore, site-directed mutagenesis was employed to change Ser-119 in the GXSXG motif to an Ala. The resulting mutant protein lost all of its lysophospholipase activity, even though it had the same overall protein conformation as that of the wild-type LysoPLA I. Therefore, LysoPLA I has been demonstrated to be a serine enzyme with Ser-119 at the active site.

Amino Acid Sequence↗
PubMed1997

Simultaneous biplane coronary and pulmonary arteriography: a novel technique for defining the course of an anomalous left main coronary artery originating from the right sinus of Valsalva.

We present a novel technique employing biplane cineangiography with simultaneous left coronary and pulmonary angiography to define the anomalous course of the left main coronary artery when it originates from the right sinus of Valsalva. These biplane cinearterlograms clearly define the relationship of the left main coronary artery to the great vessels, allowing confident delineation of the interarterial variant from the other, benign variants. We illustrate the advantages of this technique with two cases in which the course of the anomalous left main coronary artery was incorrectly diagnosed using standard coronary arteriography and magnetic resonance imaging.

Adult↗
PubMed1997

WAF1 expression and p53 mutations in human colorectal cancers.

The expression of the WAF1 gene was examined in the tissues of primary colorectal cancers and of adjacent non-neoplastic mucosas by Western blot analysis. p53 mutations of these cancer tissues were also analyzed by the polymerase chain reaction/single-strand conformation polymorphism followed by direct sequencing. Missense mutations of p53 were recognized in 19 out of 40 cases. Five cancers (12.5%) displayed much lower expression of WAF1 than did their corresponding mucosas, and all of them contained mutant p53. Fourteen cancers (35%) expressed the same level of WAF1 as their mucosas, and 5 of them had mutant p53. Twenty-one cancers (52.5%) had much higher WAF1 expression than their mucosas, and 9 of them had mutant p53. When Duke's classification was applied to these colorectal cancers, it was found that the cancers with reduced expression of WAF1 basically coincided with late (C or D) stages (4 out of 5 cases), while the cancers with higher WAF1 expression were consistent with early (A or B) stages (17 out of 21 cases). Down-regulation of WAF1 in colorectal cancer tissues may be implicated in tumor progression.

Adenocarcinoma↗
PubMed1997

Overexpression of cyclin B1 in human colorectal cancers.

The expression of the human cyclin B1 gene was investigated with Western blot analysis in human colorectal carcinomas and in adjacent non-neoplastic colorectal mucosas. Out of 41 cancers, 36 (88% of patients) showed much higher expression of cyclin B1 than did the non-neoplastic mucosa. Proliferating-cell nuclear antigen (PCNA) immunohistochemistry revealed that the labeling indexes of these cancer tissues were 47.3 +/- 11.3% while those of the mucosa were 15.6 +/- 5.5%. Only 5 cancers (12% patients) demonstrated the same expression level of cyclin B1 as the mucosa; however, the PCNA labeling indexes were 42.3 +/- 11% for the cancer tissue, compared to 12.6 +/- 2.4% for the mucosas. Southern blot analysis showed that there was no change of the cyclin B1 gene at the somatic DNA level in spite of its high expression at the protein level. These results proved that majority of colorectal cancers express high levels of cyclin B1, consistent with a high rate of cell proliferation, whereas a small fraction of these cancers lose control of cyclin B1 expression, diverging from their fast cell proliferation.

Adenocarcinoma↗
PubMed1997

Redistribution of platelet membrane glycoprotein IV and release of intracellular alpha-granule thrombospondin in patients with chronic myelogenous leukemia.

The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular alpha-granule thrombospondin (TSP) were examined and the inhibition of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in patients with chronic myelogenous leukemia (CML) was observed and quantitation of beta-TG and PF4 in sera was conducted. GPIV in inactive platelet from CML was 36080 +/- 17010 molecules/platelet as compared with 13190 +/- 4810 from the controls (P < 0.01). No abnormality was found in the distribution of platelet membrane GPIb and GPIIb/IIIa (P > 0.05). The GPIV redistribution on active platelet membrane induced thrombin (IU/ml) from CML and healthy donors was 44320 +/- 32310 and 22800 +/- 12700 molecules/platelet respectively (P < 0.01). The difference in the release of intracellular alpha-granule TSP between CML and the control group was not found (P > 0.05). There was no direct correlation between GPIV expression and TSP binding after platelet activation. The high levels of beta-TG and PF4 in sera inhibited release of intracellular alpha-granule TSP in vitro. These results indicate that the abnormality of platelet membrane GPIV is a common marker in CML, therefore the specific increase of platelet GPIV in patients with CML may be a useful tool for the diagnosis and monitoring of the platelet dysfunction. The release of internal TSP pools is hindered by either beta-TG or PF4 in sera.

CD36 Antigens↗
PubMed1997

Contraceptive practices of women requesting termination of pregnancy: a study from China.

In order to develop a program for prevention of unwanted pregnancies, we conducted a survey of contraceptive practices and reasons for contraceptive failures of 1520 women seeking abortion at eight large hospitals in Zheng Zhou City, Henan Province, P.R. China, during the period from March 1996 to May 1996. The most frequent cause of the unplanned pregnancy was contraceptive failure (71.9%) 61.7% (938) of these current pregnancies were potentially predictable by virtue of nonuse of contraception (427) or by recognition of contraceptive failures (511). Among the contraceptive failures, the proportion of condom mishaps was the highest (29.7%), next was IUD failures (23.5%), then rhythm miscalculation (15.9%). Most of abortion seekers (77.1%) used some contraceptive methods previously. But only 19.7% of them used a contraceptive method at the first sexual intercourse. Among 1520 abortion seekers. 57.6% had used condoms previously; 50.9% of the condom users had at least one instance of condom mishap. The rhythm method had been used by 31.7% of abortion seekers previously; 59.1% of the rhythm users had at least one instance of rhythm failure. Of the 16.8% of abortion seekers who had used pills, 58.0% of them had pill failures Among condom and pill failures, most of them (46.4% condom users and 56.0%, pill users) belonged to the users failure category (poor compliance). Of those seeking abortion 56.4% had experienced at least one instance of previous abortion; 5.3% had experienced previous abortions at least two times. Emergency contraception had been utilized by only 10 subjects prior to this current pregnancy.

Abortion, Induced↗
PubMed1997

Expression of a Bacillus thuringiensis cryIA(c) gene in transgenic peanut plants and its efficacy against lesser cornstalk borer.

The invasion of peanut (Arachis hypogaea L.) pods and seeds by aflatoxin-forming species of Aspergillus is linked to injury by the lesser cornstalk borer and frequently causes a severe reduction in crop quality. The lesser cornstalk borer is susceptible to the lepidopteran-active Bacillus thuringiensis insecticidal crystal protein. We have introduced a codon-modified Bacillus thuringiensis cryIA(c) gene into peanut using microprojectile bombardment. The toxin-coding region of a Bt cryIA(c) gene was reconstructed for expression in plants and the resulting 3.4 kb gene cassette (promoter: 1.8 kb coding: 3') was directly cloned into the BglII site of plant transformation vectors. The vectors contained the hph gene, conferring resistance to the antibiotic hygromycin. Somatic embryos initiated from immature peanut cotyledons of two cultivars were used as the target for bombardment. DNA from hygromycin-resistant embryogenic cell lines, regenerated plants, and a progeny plant showed the presence and integration of hph and Bt genes by PCR and/or Southern blot analyses. ELISA immunoassay of the CryIA(c) protein from the hygromycin-selected plants showed the expression of CryIA(c) protein up to 0.18% of total soluble protein. Insect feeding bioassay of transformed plants indicated various levels of resistance to the lesser cornstalk borer, from complete larval mortality to a 66% reduction in larval weight. A negative correlation between percent survival or larval weight and the amount of Bt CryIA(c) protein was recorded indicating in general that the higher the protein level the lower the survival or larval weight of the insect. Based on leaf bioassay, transformation of peanut with vectors containing the Bt cryIA(c) gene may be effective in protecting the peanut plants from damage by lepidopteran insect larvae of lesser cornstalk borer.

Animals↗
PubMed1997

Identification and characterization of human genes encoding Hprp3p and Hprp4p, interacting components of the spliceosome.

Nuclear RNA splicing occurs in an RNA-protein complex, termed the spliceosome. U4/U6 snRNP is one of four essential small nuclear ribonucleoprotein (snRNP) particles (U1, U2, U5 and U4/U6) present in the spliceosome. U4/U6 snRNP contains two snRNAs (U4 and U6) and a number of proteins. We report here the identification and characterization of two human genes encoding U4/U6-associated splicing factors, Hprp3p and Hprp4p, respectively. Hprp3p is a 77 kDa protein, which is homologous to the Saccharomyces cerevisiae splicing factor Prp3p. Amino acid sequence analysis revealed two putative homologues in Caenorhabditis elegans and Schizosaccharomyces pombe. Polyclonal antibodies against Hprp3p were generated with His-tagged Hprp3p over-produced in Escherichia coli . This splicing factor can co-immunoprecipitate with U4, U6 and U5 snRNAs, suggesting that it is present in the U4/U6.U5 tri-snRNP. Hprp4p is a 58 kDa protein homologous to yeast splicing factor Prp4p. Like yeast Prp4p, the human homologue contains repeats homologous to the beta-subunit of G-proteins. These repeats are called WD repeats because there is a highly conserved dipeptide of tryptophan and aspartic acid present at the end of each repeat. The primary amino acid sequence homology between human Hprp4p and yeast Prp4p led to the discovery of two additional WD repeats in yeast Prp4p. Structural homology between these human and yeast splicing factors and the beta-subunit of G-proteins has been identified by sequence-similarity comparison and analysis of the protein folding by threading. Structural models of Hprp4p and Prp4p with a seven-blade beta-propeller topology have been generated based on the structure of beta-transducin. Hprp3p and Hprp4p have been shown to interact with each other and the first 100 amino acids of Hprp3p are not essential for this interaction. These experiments suggest that both Hprp3p and Hprp4p are components of human spliceosomes.

Amino Acid Sequence↗
PubMed1997

[Changes of gastric pits in intestinal metaplasia of gastric mucosa].

To analyze the changes of gastric pits in intestinal metaplastic mucosa in 20 specimens of subtotal gastrorectomy and to evaluate the relationship between intestinal metaplasia and gastric pits. We made stereomicroscopic observation of the resected parts of the stomach by using dye-staining method. The width of gastric pits was measured by microscope and the histopathological examination was carried out. The features were divided into two groups: intestinal metaplasia and simple chronic superficial gastritis. The stereomicroscopic features of gastric pits were observed in 15.38% type BC, 28.21% type C, 25.64% type CD and 30.77% type D. The width of gastric pits was significantly different between intestinal metaplasia and simple superficial gastritis, especially obvious in severe intestinal metaplasia. The figures of gastric pits were mostly those a type C and type D and widened gastric pits were more obvious in intestinal metaplastic mucosa than in simple chronic superficial gastritis.

Adult↗
PubMed1997

[Hepatitis C virus infection among long-term hemodialysis patients].

We determined the prevalence and incidence of hepatitis C virus (HCV) infection among hemodialysis patients and evaluate their risk factors. 80 patients on maintenance hemodialysis in Peking Union Medical College Hospital Dialysis Center from December 1994 to June 1995 were studied. 30 medical students were used as health controls. Serum samples were tested for HCV antibodies by a second-generation enzyme-linked immunosorbent assay (ELISA) and for HCV RNA using nested polymerase chain reaction (PCR) and retested for anti-HCV and HCV RNA three months later. 24 (30%) of 80 hemodialysis patients were anti-HCV positive, and 2 (3.6%) of 56 anti-HCV negative cases were found HCV RNA positive. By combined assessment, the HCV infection rate of hemodialysis patient was 32.5% (26/80). Mantel-Haenszel analysis showed that HCV infection was associated with multi-transfusions, dialysis over a long period, renal transplantation, history of operation. Samples of dialysate in 9 serum HCV RNA positive cases were directly detected for HCV RNA, and 3 were found HCV RNA detectable. HCV infection rate in hemodialysis patients is higher than that of general population. The main risk factors for HCV transmission is transfusion of unscreened blood but is not an independent factor, hemodialysis itself plays an important role, the length of time on dialysis, renal transplantation, blood-contaminated material and contaminated dialysis equipment are also the risk factors. Infected hemodialysis patients should be isolated.

Adult↗