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Biomedical subjects

Y Xue

Publications and source records attributed to Y Xue.

At least 181 records · Page 10Linked to original sources
PubMed1996

Angiogenin single-chain immunofusions: influence of peptide linkers and spacers between fusion protein domains.

The gene for human angiogenin (Ang), a member of the ribonuclease superfamily, was fused to a gene encoding a single-chain antibody (sFv) against the human transferrin receptor. Three Ang single-chain immunofusion proteins (AngsFvs) were constructed with variations in the type of linker connecting the VL and VH chain [EGKSSGSGSESKEF, L1 or (GGGGS)3, L2] as well as with or without a spacer (FB) connecting the Ang and sFv (AngFBsFvL1 or L2; AngsFv(L2)]. Although the nature of the linker did not affect the enzymatic activity of the FB-containing fusion proteins, the fusion protein containing the L2 linker was 2.3-fold more effective than the L1 linker in competing with the labeled monoclonal IgG1 antibody for binding to the transferrin receptor. The fusion protein containing the L2 linker without the FB spacer exhibited a 13-fold decrease in binding to the transferrin receptor as well as a decrease in its capacity to degrade tRNA and to inhibit translation in the rabbit reticulocyte lysate compared to its counterpart containing the FB spacer. Binding of placental ribonuclease inhibitor (PRI) to Ang also was affected by the nature of the linker and by the presence or absence of a spacer. PRI bound to Ang and AngFBsFv(L2) and inhibited their ribonuclease activity. A 3-fold greater concentration of PRI, however, did not affect the activity of AngFBsFv(L1) or AngsFv(L2), suggesting that the conformation of these fusion proteins was altered. Binding of monoclonal and polyclonal anti-Ang antibodies to AngsFvs was also used to investigate conformational alterations of the fusion proteins. AngFBsFv(L2) was the least altered while AngFBsFv(L1) exhibited the greatest change in structure. Yet maximal concentrations of all AngsFvs elicited angiogenesis in the chick chorioallantoic membrane assay, demonstrating that Ang in all three fusion proteins remained functionally active. Consistent with all the activities, the fusion protein containing the FB spacer and L2 linker was the most cytotoxic to three different human tumor cell lines. The fusion protein lacking the FB spacer exhibited the least cytotoxicity. These data demonstrate that the linker connecting the VH-VL chains can affect the binding and cellular cytotoxicity of Ang immunofusions and that placement of a spacer between the antibody binding domains and Ang is necessary for optimal activity. Thus, a new class of targeted therapeutic agents containing Ang as the toxic moiety can be designed that potentially will be less immunogenic and less toxic than immunotoxins available currently.

Amino Acid Sequence↗
PubMed1996

Inhibition of I-Ad-, but not Db-restricted peptide-induced thymic apoptosis by glucocorticoid receptor antagonist RU486 in T cell receptor transgenic mice.

Thymocytes differentiate by positive and negative selection of immature CD4+ CD8+ T cells. Negative selection occurs by default or by high-affinity recognition of peptides bound to proteins encoded by the major histocompatibility complex (MHC). MHC class I molecules are expressed on many different cell types, although at different levels, whereas MHC class II molecules are selectively expressed on thymic epithelial cells (TEC) and dendritic cells (DC). We investigated the role of the glucocorticoid receptor (GR) in thymic negative selection using the receptor antagonist RU486. Glucocorticoids (GC) are known to be potent inducers of apoptosis in CD4+ CD8+ thymocytes, and we have earlier shown that anti-CD3-induced thymic apoptosis can be blocked by RU486 in vivo. We now show that anti-CD3 induces thymic apoptosis in mice that have been adrenalectomized (ADX), and that RU486 inhibits anti-CD3 antibody-mediated thymocyte killing in newborn thymic organ cultures. Thymocyte apoptosis induced by ovalbumin peptide OVA323-339 treatment of mice transgenic for the DO11.10T cell receptor (TCR), which recognizes this peptide in the context of I-Ad, was found to be inhibited by RU486. These mice responded to peptide treatment by an extensive activation of the peripheral immune system, which became lethal in 60% of the mice when accompanied by simultaneous RU486 treatment. In contrast, RU486 had no effect on thymic apoptosis induced by the influenza A nucleoprotein NP366-374 peptide, recognized in context of Db, in F5 TCR transgenic mice. We interpret the results to demonstrate that different deletion systems operate in the thymus. We propose that endogenous GC may be important for negative selection by default and by high-affinity recognition of endogenous MHC-presented peptides on TEC.

Amino Acid Sequence↗
PubMed1996

Tetraploid or near-tetraploid clones characterized by two 8;21 translocations and other chromosomal abnormalities in two patients with acute myeloblastic leukemia.

Acute myeloblastic leukemia (AML) with tetraploidy is rare. There have been only six such cases studied with banding techniques in the literature. Two were diagnosed as having AML-M2 and found to have similar near-tetraploid karyotypes with t(8;21) and missing Y chromosomes. We report two further cases of AML with tetraploid or near-tetraploid clones characterized by two t(8;21) and other chromosomal changes. Their cytogenetic findings were compatible with the diagnosis of AML-M2. Giant and bizarre blasts were seen on bone marrow (BM) smears from both cases. Immunologically, the blasts express CD2, CD15, and HLA-DR in case 1 and CD2 and CD65 in case 2. Cytogenetic studies on BM cells at diagnosis revealed that both cases had three related abnormal clones besides a normal one: 46,XY,t(8;21) (2%)/46,idem,add(7)(q31)(6.8%)/92, idem x 2 (80.6%) for case 1; and 46,XX,t(8;21)(13.4%)/47, idem,+4 (46.3%)/94,idem x 2 (39.1%) for case 2. Flow cytometric analysis displayed two cell populations in the former: one was in the diploid range and the other was in the tetraploid range. The patients did not obtain complete remissions and survived four and six months, respectively. These results indicate that tetraploid or near-tetraploid clones are secondary events which are associated with t(8;21) leukemia and may be associated with poor prognostic significance.

Adult↗
PubMed1996

Karyotype conversion in two patients with chronic myeloid leukaemia after busulphan-induced marrow hypoplasia.

SUMMARY: We report two patients with chronic myeloid leukaemia (CML) developing hypoplasia and karyotype conversion after conventional busulphan therapy. Initially, the percentage of Ph-positive metaphases in marrow for both patients was 100%, which steadily diminished up to a complete disappearance in case 1 and decreased dramatically in case 2 following hypoplasia. Thereafter Southern blot and RT-PCR assays revealed no abnormalities. Both patients have survived 9 years and remained in good clinical and haematological remission without any treatment until recently. We believe that the high sensitivity to busulphan therapy result in hypoplasia and karyotype conversion, which contributed to prolonged survival.

Adult↗
PubMed1996

Antiarrhythmic effects of optical isomers of disopyramide on canine ventricular arrhythmias.

Disopyramide is an effective class I antiarrhythmic drug and widely used for the treatment of arrhythmias, but it has anticholinergic side effects. In vitro studies demonstrated that dextrorotatory (D-) disopyramide has a stronger anticholinergic action, whereas the levorotatory (L-) isomer has a stronger Na channel blocking action. Because the antiarrhythmic mechanism of disopyramide suppressing digitalis- and two-stage coronary ligation-induced canine ventricular arrhythmias is the drug-induced Na channel block, we examined the antiarrhythmic efficacy of D- and L-disopyramide on two arrhythmia models. On ouabain-induced ventricular tachycardia (VT), L-disopyramide 3 mg/kg decreased the arrhythmic ratio (number of ectopic beats/total heart rate), whereas the same dose of the D-isomer was ineffective and a higher dose (5 mg/kg) was needed to suppress the arrhythmia. The effective plasma concentrations (IC50) decreasing the arrhythmic ratio to 50% of the control were 5.3 and 11.3 mu g/ml for L- and D-disopyramide, respectively. We obtained similar results using 24-h two-stage coronary ligation VT. The IC50 were 8.9 and 22.2 mu g/ml for the L- and D-isomers, respectively. Our results indicate that L-disopyramide is about twice as strong an antiarrhythmic drug as the D-isomer.

Action Potentials↗
PubMed1996

Effects of dofetilide, a class III antiarrhythmic drug, on various ventricular arrhythmias in dogs.

Dofetilide, a new class III antiarrhythmic agent, was tested in various kinds of canine ventricular arrhythmias to compare its effects with those of other class III agents. Ventricular arrhythmia models used were induced by two-stage coronary ligation, digitalis, epinephrine, coronary ligation and reperfusion, and programmed electrical stimulation (PES). Dofetilide (100 micrograms/kg intravenously) did not suppress automaticity arrhythmias induced by two-stage coronary ligation and epinephrine or the coronary ligation and reperfusion arrhythmias, but suppressed the reentry arrhythmia induced by PES in dogs with old myocardial infarction (MI). This effect was associated with a prolongation of QT interval. Dofetilide also showed antiarrhythmic effect in some dogs with digitalis arrhythmia. Dofetilide increased QT interval and showed negative chronotropic effect like that of other class III drugs, but was different in antiarrhythmic profiles from those of other class III agents such as D-sotalol, E-4031, and MS-551 in that it did not prevent the occurrence of ventricular fibrillation (VF) immediately after coronary reperfusion and had some antiarrhythmic effects on digitalis arrhythmia.

Animals↗
PubMed1996

Origin of allelic diversity in antirrhinum S locus RNases.

In many plant species, self-incompatibility (SI) is genetically controlled by a single multiallelic S locus. Previous analysis of S alleles in the Solanaceae, in which S locus ribonucleases (S RNases) are responsible for stylar expression of SI, has demonstrated that allelic diversity predated speciation within this family. To understand how allelic diversity has evolved, we investigated the molecular basis of gametophytic SI in Antirrhinum, a member of the Scrophulariaceae, which is closely related to the Solanaceae. We have characterized three Antirrhinum cDNAs encoding polypeptides homologous to S RNases and shown that they are encoded by genes at the S locus. RNA in situ hybridization revealed that the Antirrhinum S RNase are primarily expressed in the stylar transmitting tissue. This expression is consistent with their proposed role in arresting the growth of self-pollen tubes. S alleles from the Scrophulariaceae form a separate group from those of the Solanaceae, indicating that new S alleles have been generated since these families separated (approximately 40 million years). We propose that the recruitment of an ancestral RNase gene into SI occurred during an early stage of angiosperm evolution and that, since that time, new alleles subsequently have arisen at a low rate.

Amino Acid Sequence↗
PubMed1996

The two major spore DNA repair pathways, nucleotide excision repair and spore photoproduct lyase, are sufficient for the resistance of Bacillus subtilis spores to artificial UV-C and UV-B but not to solar radiation.

Bacterial endospores are 1 to 2 orders of magnitude more resistant to 254-nm UV (UV-C) radiation than are exponentially growing cells of the same strain. This high UV resistance is due to two related phenomena: (i) DNA of dormant spores irradiated with 254-nm UV accumulates mainly a unique thymine dimer called the spore photoproduct (SP), and (ii) SP is corrected during spore germination by two major DNA repair pathways, nucleotide excision repair (NER) and an SP-specific enzyme called SP lyase. To date, it has been assumed that these two factors also account for resistance of bacterial spores to solar UV in the environment, despite the fact that sunlight at the Earth's surface consists of UV-B, UV-A, visible, and infrared wavelengths of approximately 290 nm and longer. To test this assumption, isogenic strains of Bacillus subtilis lacking either the NER or SP lyase DNA repair pathway were assayed for their relative resistance to radiation at a number of UV wavelengths, including UV-C (254 nm), UV-B (290 to 320 nm), full-spectrum sunlight, and sunlight from which the UV-B portion had been removed. For purposes of direct comparison, spore UV resistance levels were determined with respect to a calibrated biological dosimeter consisting of a mixture of wild-type spores and spores lacking both DNA repair systems. It was observed that the relative contributions of the two pathways to spore UV resistance change depending on the UV wavelengths used in a manner suggesting that spores irradiated with light at environmentally relevant UV wavelengths may accumulate significant amounts of one or more DNA photoproducts in addition to SP. Furthermore, it was noted that upon exposure to increasing wavelengths, wild-type spores decreased in their UV resistance from 33-fold (UV-C) to 12-fold (UV-B plus UV-A sunlight) to 6-fold (UV-A sunlight alone) more resistant than mutants lacking both DNA repair systems, suggesting that at increasing solar UV wavelengths, spores are inactivated either by DNA damage not reparable by the NER or SP lyase system, damage caused to photosensitive molecules other than DNA, or both.

Bacillus subtilis↗
PubMed1996

[Classification of ninety-eight adult cases of acute leukemia according to morphology, immunology and cytogenetics].

Ninety-eight cases of adult acute leukemia (AL) were diagnosed and classified based on morphologic, immunologic and cytogenetic (MIC) features. The results showed that: the conformity rate of cytomorphologic/cytochemical classification with MIC classification was 90.8%. For ALL, the conformity rate of immunologic classification with MIC classification was 95.6%, but it was only 70.8% for AML. Of the 48 AML, 10 expressed lymphoid lineage, associated antigens and 8 of 43 ALL expressed myeloid lineage-associated antigens. Seven cases were diagnosed as hybrid acute leukemia according to Catovsky criterion. The chromosome aberrations were found in 70 cases, of them 46 cases showed characteristic abnormalities including t(9;22), t(4;11), t(11;14), t(8;12), t(8;14), 6q-, 9p-, and t(15;17), t(8;21), inv(16), etc.

Adolescent↗
PubMed1996

[A study on the diagnostic criteria for adult acute myeloid leukemia with morphology, immunology and cytogenetics].

This study was undertaken to establish the more reasonable criteria for diagnosis of acute myeloid leukemia (AML). 82 cases diagnosed initially or finally as AML were analyzed with morphology, immunology and cytogenetics (MIC). The results revealed that 89.0% of the pretherapy morphology conformed to MIC and 93.9% of the immunology conformed to it. 4 cases with hybrid acute leukemia (HAL), one case with acute undifferentiated leukemia (AUL) and one case with acute B-Acute lymphocytic leukemia were confirmed with MIC. The positive expression of myeloid markers on samples from 76 cases of AML was followed by CD33 > CD13 > CD65, SI6 > CD15 > CD11b > CD14, but not specific for AML subtypes. The lymphoid antigens CD2, CD7, CD10 and CD19 were positive in minority of the cases of AML, but CD2+ and CD7+ were easily found in M3 and M1 speerately. 55.4% of the patients with AML in this group showed abnormality in cytogenetics. Typical t(8;21) or its variants was found in 14/24 cases of M2 and one case of M1; t(7;11) (P15;P15) in one case of M2; t(15;17) in 4/7 cases of M3; and inv(16) in one case of M4E0. It is shown that MIC classificassion is more helpful than any signgle one of the three in diagnosis of AML, especially of HAL, AUL, Mo.

Adolescent↗
PubMed1996

[Application of monoclonal antibody immuno-colloide gold probe in the study of porphyromonas gingivalis].

Immuno-electron localization of McAb BGG9 was specific for Porphyromonas gingivalis labeled with colloide gold. The monoclonal antibody immuno-colloide gold probe reacted with Porphyromonas gingivalis and 5 species of black pigmented bacteroides groups. The bacteria were fixed and embbed in Epon. sections were examined under transmission electron microscope, and the gold granular was observed near Porphyromonas gingivalis cell membrane. Our conclusion suggests that monoclonal antibody immuno-colloide gold probe is useful tool for studying Porphyromonas gingivalis.

Antibodies, Bacterial↗
PubMed1996

[The path of gastric lymphatic drainage and its significance for redical resection of gastric carcinoma].

By dissecting 31 corpses' stomach and then thining the gastric lymphatic system with prussian blue staining, we found out that the gastric lymphatic return from the visceral surface to the parietal pleura mainly takes three ways: a lymphatic nodes of the coelica artery trunk, a lymphatic nodes beside the superior mesenteric artery, and lymphatic nodes beside the left inferior phrenic. The lympha of these paths flew to the parietal pleura around the left renal viens. This result can give reference to cleaning lymphatic nodes beside abdominal aorta during the radical operation of gastric carcinoma.

Aorta, Abdominal↗
PubMed1996

[Studies on purification and some properties of nisin from Lactococcus lactis subsp. lactis Al2].

Nisin from Lactococcus lactis subsp. lactis AL2 was extracted with n-propanol from NaCl-saturated culture and purified by ion-exchange chromotography on CM-Sephadex C-25. Nisin was purified 1.63 fold with a yield of 41.7%. The molecular weight of nisin was determined by SDS-PAGE to be about 3500. Nisin activity was stable at low pH and sensitive to digestion by a-chymotrypsin. Nisin is capable of inhibiting a broad range of gram-positive bacteria. In contrast, the gram-negative bacteria, yeasts, molds and Nip+ L. lactis subsp. lactis ATCC11454 were not inhibited.

Anti-Bacterial Agents↗
PubMed1995

Location of the active site of allosteric chorismate mutase from Saccharomyces cerevisiae, and comments on the catalytic and regulatory mechanisms.

The active site of the allosteric chorismate mutase (chorismate pyruvatemutase, EC 5.4.99.5) from yeast Saccharomyces cerevisiae (YCM) was located by comparison with the mutase domain (ECM) of chorismate mutase/prephenate dehydratase [prephenate hydro-lyase (decarboxylating), EC 4.2.1.51] (the P protein) from Escherichia coli. Active site domains of these two enzymes show very similar four-helix bundles, each of 94 residues which superimpose with a rms deviation of 1.06 A. Of the seven active site residues, four are conserved: the two arginines, which bind to the inhibitor's two carboxylates; the lysine, which binds to the ether oxygen; and the glutamate, which binds to the inhibitor's hydroxyl group in ECM and presumably in YCM. The other three residues in YCM (ECM) are Thr-242 (Ser-84), Asn-194 (Asp-48), and Glu-246 (Gln-88). This Glu-246, modeled close to the ether oxygen of chorismate in YCM, may function as a polarizing or ionizable group, which provides another facet to the catalytic mechanism.

Allosteric Regulation↗
PubMed1995

Crystal structure of spinach chloroplast fructose-1,6-bisphosphatase at 2.8 A resolution.

The three-dimensional structure of the spinach chloroplast fructose-1,6-bisphosphatase (Fru-1,6-Pase) has been solved by the molecular replacement method at 2.8 A resolution and refined to a crystallographic R factor of 0.203. The enzyme is composed of four monomers and displays pseudo D2 symmetry. Comparison with the allosteric Fru-1,6-Pase from pig kidney shows orientationally displaced dimers within the quaternary structure of the chloroplast enzyme. When the C1C2 dimers of the two enzymes are superimposed, the C3C4 dimer of the chloroplast enzyme is rotated 20 degrees and 5 degrees relative to the C3C4 dimer of the R and T forms of the pig kidney enzyme, respectively. This new quaternary structure, designated as S, may be described as a super-T form and is outside of the pathway of the allosteric transition which occurs in the pig kidney enzyme, which shows a 15 degrees rotation between T and R forms. Chloroplast Fru-1,6-Pase, unlike the pig kidney enzyme, is insensitive to allosteric transformation by AMP. Structural changes in the AMP binding site involving mainly helices H1, H2, and H3 and the loop between H1 and H2 at the dimer interface interfere with binding of the phosphate of AMP. Finally, the location of cysteines residues provides a basis for a preliminary discussion of the activation of the enzyme by reduction of cysteines via the ferredoxin-thioredoxin f system; this process is complementary to activation by pH changes, Mg2+ or Ca2+, Fru-1,6-P2, and possibly Fru-2,6-P2.

Adenosine Monophosphate↗
PubMed1995

An isochromosome of the long arm of chromosome 18 in a patient with myelodysplastic syndrome with myelofibrosis.

A case of myelodysplastic syndrome (MDS) with myelofibrosis and i(18q) is reported. The patient, a 29-year-old Chinese man, was noted to be anemic over a 10-year period. Recently, his spleen became progressively massive and bone marrow aspirates yielded "dry taps" on several occasions. Hematologic investigation disclosed pancytopenia, numerous nucleated red cells, and slightly increased myeloblasts (8%) in the peripheral blood. Bone marrow aspirate and biopsy revealed hypercellular marrow, trilineage dysplasia, and significant reticulin fibrosis, but without collagen formation. Bone marrow karyotypic analysis with R-banding showed an isochromosome 18q as a sole abnormality in 20 of 24 metaphases analysed. The patient died of severe anemia and bleeding due to bone marrow failure. We believe that i(18q) and myelofibrosis may be related to his poor prognosis.

Adult↗
PubMed1995

Simultaneous targeting of pea glutathione reductase and of a bacterial fusion protein to chloroplasts and mitochondria in transgenic tobacco.

N-terminal presequences from cDNAs encoding mitochondrion- or chloroplast-specific proteins are able, with variable efficiencies, to target preproteins to their respective organelles. In the few cases studied in which a nuclear-encoded protein is found in both these organelles, each compartment-specific isoform is encoded by a separate gene. Glutathione reductase (GR) from peas is encoded by a single nuclear gene and yet GR is distributed between chloroplasts, mitochondria and the cytosol. Previous sequence analysis of a full-length GR cDNA revealed the presence of a putative plastid transit peptide. However, expression of this cDNA in transgenic tobacco resulted in substantially elevated GR activities in both chloroplasts and mitochondria in four independent lines examined. There was no effect on expression of the endogenous tobacco GR genes. Replacement of the GR presequence with presequences from pea rbcS (chloroplast) and Nicotiana plumbaginifolia Mn-SOD (mitochondrion) resulted in targeting of GR only into the appropriate organelle. Expression of a fusion protein between the amino terminal region of GR and phosphinothricin acetyl transferase resulted in targeting of the foreign protein to chloroplasts and mitochondria. Thus, the pea GR presequence is capable of co-targeting this enzyme or a foreign protein to chloroplasts and mitochondria in vivo. This is the first example of co-targeting by a higher plant preprotein.

Acetyltransferases↗