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Biomedical subjects

L Yang

Publications and source records attributed to L Yang.

At least 811 records · Page 45Linked to original sources
PubMed1986

[Fetal liver cell transfusion in chemotherapy of malignant tumors and blood diseases].

From Feb. to Dec. 1985, 15 patients were treated with fetal liver cell transfusion (FLT). They were 10 cases with malignant tumors treated by chemotherapy (tumor group) and 5 with blood diseases (blood group). Under strict aseptic technique, 3 1/2-6 month old fetus was selected for preparing suspension of the fetal liver cells on the superclean table. The speed of FLT should be increased gradually from slow to rapid. There are 1.8 X 10(8)-4 X 10(12) fetal liver cells in a fetus of more than 5 months old, in which most are CFU-C. In the tumor group, after FLT, white blood cell, platelet and hemoglobin increased by 700-3,900/mm3, 5,000-116,000/mm3 and 0.5-2.0 gm/mm3 respectively. But in the blood group, they increased by 800-1,300/mm3, 14,000-84,000/mm3 and 0.4-11.0 gm/mm3. In most of the cases, these hematological indexes reached up to the highest in 2 weeks after FLT. It suggests that FLT can improve the peripheral blood picture obviously and stimulate bone marrow. Experiment confirms that there are considerable hematopoietic stem cells in the fetal liver, by which the functions of hematopoiesis and immunity are able to recover. It is more marked in the tumor group than in the blood group. FLT provides a favourable condition for high dose chemotherapy.

Agranulocytosis↗
PubMed1985

In vivo mapping of DNA topoisomerase II-specific cleavage sites on SV40 chromatin.

The antitumor drug, m-AMSA (4'-(9-acridinylamino)-methanesulfon-m-anisidide), is known to interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II by blocking the enzyme-DNA complex in its putative cleavable state. Treatment of SV40 virus infected monkey cells with m-AMSA resulted in both single- and double-stranded breaks on SV40 viral chromatin. These strand breaks are unusual because they are covalently associated with protein. Immunoprecipitation results suggest that the covalently linked protein is DNA topoisomerase II. These results are consistent with the proposal that the drug action in vivo involves the stabilization of a cleavable complex between topoisomerase II and DNA in chromatin. Mapping of these double-stranded breaks on SV40 viral DNA revealed multiple topoisomerase II cleavage sites. A major topoisomerase II cleavage site was preferentially induced during late infection and was mapped in the DNAase I hypersensitive region of SV40 chromatin.

Aminoacridines↗
PubMed1985

Isolation of stable preinitiation, initiation, and elongation complexes from RNA polymerase II-directed transcription.

Distinct RNA polymerase II transcription preinitiation, initiation, and elongation complexes can be formed in vitro on cloned adenovirus 2 DNA sequences containing the major late promoter. These transcription complexes are stable and can be rapidly isolated by gel filtration of HeLa whole cell extracts. In the absence of exogenous nucleotides and under appropriate salt conditions, a stable but transcriptionally incomplete preinitiation complex is formed. When this complex is incubated in the presence of adenosine or deoxyadenosine triphosphates, the beta-gamma phosphodiester bond is hydrolyzed, and RNA polymerase II joins the complex, thereby converting it into a stable initiation complex capable of forming (but prior to the formation of) the first phosphodiester bond. When this complex is isolated and incubated in the presence of all four nucleoside triphosphates, it is converted into an elongation complex that then permits the synthesis of phosphodiester bonds and the correct run-off transcript. A limiting transcription component is sequestered in the preinitiation complex. This factor is released upon elongation and can reassociate with new DNA templates during subsequent rounds of initiation. Therefore, class II genes do not appear to form activated transcription units stable for multiple rounds of transcription; rather, their transcriptional activity may be controlled in part by regulating the association of transcription factors at each initiation event.

Adenoviridae↗
PubMed1985

Patterns of psychiatric consultation in a Chinese general hospital.

The authors conducted a study of psychiatric consultation in a Chinese general hospital. Seventy-five inpatients (0.74% of the patients in the hospital) were referred by different services over a 1-year period. Internal medicine referred the most patients, and organic brain syndromes were the most common diagnoses. Depression was not a frequent diagnosis, but neurasthenia was a fairly common one. None of the referred patients had a diagnosis of alcoholism, drug abuse, or personality disorder. The authors compare these data with those of Western studies and discuss the possible factors influencing psychiatric consultation in China.

Adolescent↗
PubMed1985

Identification of DNA topoisomerase II as an intracellular target of antitumor epipodophyllotoxins in simian virus 40-infected monkey cells.

The effect of antitumor epipodophyllotoxins, etoposide (VP-16) and teniposide (VM-26), on chromosomal DNA in mammalian cells was studied using SV40 virus-infected monkey cells as a model system. Treatment of SV40 virus-infected monkey cells with these drugs results in DNA breaks on intracellular SV40 DNA. The broken DNA strands are sensitive to phenol extraction, suggesting that they are associated with tightly linked protein(s). Several pieces of evidence suggest that DNA topoisomerase II is covalently linked to the broken SV40 DNA strands following drug treatment. ovobiocin, an inhibitor of topoisomerase II, blocks the epipodophyllotoxin-induced SV40 DNA breaks in vivo and in vitro. Epipodophyllotoxin-induced cleavage sites on intracellular SV40 DNA are strikingly similar to those produced on purified SV40 DNA by purified calf thymus DNA topoisomerase II. The protein-linked SV40 DNA is specifically immunoprecipitated by antisera against topoisomerase II. We thus conclude that epipodophyllotoxins induce chromosomal DNA breakage via DNA topoisomerase II. The physiological effects of epipodophyllotoxins on cell death, chromosomal DNA breakage, sister chromatid exchanges, and chromosomal aberrations may be the consequence of drug interaction with DNA topoisomerase II. Our present results are also consistent with the proposal that epipodophyllotoxins interfere with the breakage-reunion reaction of DNA topoisomerase II by stabilizing an enzyme-DNA complex in its putative cleavable state.

Animals↗
PubMed1984

Nonintercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II.

Many intercalative antitumor drugs have been shown to cleave DNA indirectly through their specific effect on the stabilization of a cleavable complex formed between mammalian DNA topoisomerase II and DNA (Nelson, E.M., Tewey, K.M., and Liu, L.F. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 1361-1365). Antitumor epipodophyllotoxins (VP-16 and VM-26) which do not intercalate DNA can similarly induce protein-linked DNA breaks in cultured mammalian cells. In vitro studies using purified mammalian DNA topoisomerase II show that epipodophyllotoxins interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II by stabilizing a cleavable complex. Treatment of this stabilized cleavable complex with protein denaturants results in DNA strand breaks and the covalent linking of a topoisomerase subunit to the 5'-end of the broken DNA. Furthermore, epipodophyllotoxins also inhibit the strand-passing activity of mammalian DNA topoisomerase II, presumably as a result of drug-enzyme interaction. The agreement between the in vivo and in vitro studies suggests that mammalian DNA topoisomerase II is a drug target in vivo. The similarity between the effect of epipodophyllotoxins on mammalian DNA topoisomerase II and the effect of nalidixic acid on Escherichia coli DNA gyrase suggests that the cytotoxic action of epipodophyllotoxins may be analogous to the bactericidal action of nalidixic acid.

Animals↗
PubMed1984

Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II.

Adriamycin (doxorubicin), a potent antitumor drug in clinical use, interacts with nucleic acids and cell membranes, but the molecular basis for its antitumor activity is unknown. Similar to a number of intercalative antitumor drugs and nonintercalative epipodophyllotoxins (VP-16 and VM-26), adriamycin has been shown to induce single- and double-strand breaks in DNA. These strand breaks are unusual because a covalently bound protein appears to be associated with each broken phosphodiester bond. In studies in vitro, mammalian DNA topoisomerase II mediates DNA damage by adriamycin and other related antitumor drugs.

Adenosine Triphosphate↗
PubMed1984

Isolation of an active transcription initiation complex from HeLa cell-free extract.

A two-step procedure has been developed for the formation of RNA polymerase II transcription initiation and elongation complexes. Initiation complexes are rapidly formed in HeLa cell-free extract supplemented with a DNA template containing the adenovirus 2 major late promoter and ATP. Assembly of transcription components required for correct initiation is absolutely dependent on specific eukaryotic promoter sequences. Sarkosyl-sensitive transcription initiation complexes are rapidly converted to Sarkosyl-resistant elongation complexes when supplemented with the remaining nucleoside triphosphates. The 60S initiation complex can be extensively purified by glycerol gradient centrifugation and is easily separated from free RNA polymerase II and free DNA template. Recovery of this stable complex is greater than 90%. Specific transcription cannot be detected if the DNA template is subsequently added to gradient fractions containing HeLa cell-free extract components alone. This suggests that the DNA templates promote the specific assembly of RNA polymerase II and transcription factors required for accurate initiation. Since conversion of purified initiation complexes to elongation complexes can occur without additional HeLa cell components, the presence of transcription components required for initiation and elongation in a single complex is indicated.

Cell-Free System↗
PubMed1984

Homologous globin cell-free transcription system with comparison of heterologous factors.

Mouse erythroleukemia (MEL) cells provide a useful model system to examine the regulation of globin gene expression. MEL cells ordinarily do not express globin genes, but in the presence of inducers, such as dimethyl sulfoxide or hexamethylene bisacetamide, they mimic erythroid differentiation. We have developed a cell-free transcription system from uninduced MEL cells to determine the requirements for mRNA synthesis. The MEL system directs accurate transcription of adenovirus type 2 major late DNA and mouse betamaj-globin with an efficiency comparable to those of HeLa and KB cell extracts. Using the procedure of Matsui et al. (T. Matsui, J. Segall, P.A. Weil, and R.G. Roeder, J. Biol. Chem. 255:11992-11996, 1980), we have isolated three active fractions from both MEL and HeLa cell extracts which are required for accurate transcription and have shown that equivalent fractions from MEL and HeLa cell extracts are interchangeable. Our findings suggest that the components required for initiation of transcription are similar in different cell types, at least to the extent that they can be assayed in these in vitro systems.

Animals↗
PubMed1983

Cleavage of DNA by mammalian DNA topoisomerase II.

Using the P4 unknotting assay, DNA topoisomerase II has been purified from several mammalian cells. Similar to prokaryotic DNA gyrase, mammalian DNA topoisomerase II can cleave double-stranded DNA and be trapped as a covalent protein-DNA complex. This cleavage reaction requires protein denaturant treatment of the topoisomerase II-DNA complex and is reversible with respect to salt and temperature. The product after reversal of the cleavage reaction remains supertwisted, suggesting that the two ends of the putatively broken DNA are held tightly by the topoisomerase. Alternatively, the enzyme-DNA interaction is noncovalent, and the covalent linking of topoisomerase to DNA is induced by the protein denaturant. Detailed characterization of the cleavage products has revealed that topoisomerase II cuts DNA with a four-base stagger and is covalently linked to the protruding 5'-phosphoryl ends of each broken DNA strand. Calf thymus DNA topoisomerase II cuts SV40 DNA at multiple and specific sites. However, no sequence homology has been found among the cleavage sites as determined by direct nucleotide-sequencing studies.

Animals↗