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Biomedical subjects

Q Xu

Publications and source records attributed to Q Xu.

At least 415 records · Page 23Linked to original sources
PubMed1993

Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis.

Arteriosclerotic lesions can be induced in normocholesterolaemic rabbits by immunisation with heat-shock protein (hsp) 65, a stress protein expressed in high concentrations in human atherosclerotic lesions. If an immune reaction to hsp65 also plays a part in human atherogenesis, it should be possible to detect anti-hsp65 antibodies in patients with atherosclerotic lesions. To study the possible relation between immune reaction to hsp65 and atherosclerosis, 867 normal inhabitants of South Tyrol, aged 40-79 years, were selected randomly for determination of serum antibodies against hsp65, simultaneous sonographic assessment of carotid atherosclerotic lesions, and evaluation of established risk factors--ie, blood cholesterol, hypertension, smoking, diabetes mellitus, and obesity. Autoantibodies to nuclear antigens, thyroid antigens, and rheumatoid factors were also measured. Serum anti-hsp65 antibodies were significantly (p < 0.05) increased in subjects aged 60-79 years with carotid atherosclerosis compared with those without lesions, and increased antibody concentration was independent of age, sex, and other established risk factors. On the other hand, the incidence and titres of autoantibodies did not correlate with carotid atherosclerotic lesions. Our data provide the first evidence of a strong correlation between anti-hsp65 antibodies and carotid atherosclerosis, suggesting that hsp65 might be involved in the pathogenesis of atherosclerosis.

Adult↗
PubMed1993

Establishment of National Quality Control Reference Panels and Requirements for Hepatitis B diagnosis reagents in China.

A National Quality Control Reference Panel for Hepatitis B Diagnostic Kits has been established. Markers for these standards which were prepared include National Standards for HBsAg and anti-HBs calibrated against WHO International Standards. In addition, Reference Panels for HBeAg, anti-HBe, anti-HBc, anti-HBc IgM and HBV were established and National Requirements set. These panels have been used for the nationwide evaluation of HB kits and for licensing purposes.

China↗
PubMed1993

Direct genotyping and prenatal diagnosis of beta-thalassemia in Chinese by polymerase chain reaction mediated restriction fragment length polymorphism method.

The molecular basis of beta-thalassemia is predominantly point mutations in the beta-globin gene. Frameshift 41-42 (-CTTT), IVS-2 position 654 (C-->T) mutation, nonsense codon 17 (A-->T), TATA box position -28 (A-->G) mutation and frameshift 71-72 (+A) account for more than 95% of beta-thalassemia alleles in the population of South China. We have developed a polymerase chain reaction (PCR)-mediated restriction fragment length polymorphism (RFLP) method for the identification of these alleles. In this method, artificial mispairing bases in PCR-amplified products were created to distinguish normal from mutant alleles on the basis of RFLPs. The size of the five PCR-amplified DNA fragments that may potentially contain the above five types of mutations is 93 or 89 bp (codons 41-42), 221 bp (IVS-2 nt 654), 110 bp (codon 17), 123 bp (TATA box nt -28), and 97 or 98 bp (codons 71-72). After these fragments were digested with Hinc II, Mae III, Nhe I, EcoR I, and Dde I, respectively, the allele-specific RFLPs produced were analyzed by gel electrophoresis. DNA samples of 24 patients with the above five types of beta-thalassemia were investigated with the present method and allele-specific oligonucleotide (ASO) probing simultaneously. We used this method in the prenatal diagnosis of 14 Chinese families for beta-thalassemia. The results obtained by the present method correspond well with those by the ASO probe test.

Adult↗
PubMed1993

Induction of B-A transitions of deoxyoligonucleotides by multivalent cations in dilute aqueous solution.

Circular dichroism (CD) spectra of d(CCCCGGGG) in the presence of Co(NH3)6(3+) are very similar to spectra of r(CCCCGGGG). In contrast, B-form characteristics are observed for d(CCCCGGGG) in the presence of Na+ and Mg2+, even at high salt concentrations. Spermidine induces modest changes of the CD of d(CCCCGGGG). The NMR chemical shifts of the nonexchangeable protons of d(CCCCGGGG) in the absence and presence of Co(NH3)6(3+) were assigned by proton two-dimensional (2D) NOESY and COSY measurements. The chemical shifts of the GH8 protons of d(CCCCGGGG) move upfield upon titration with Co(NH3)6Cl3. The sums of the sugar H1' coupling constants decrease with added Co(NH3)6Cl3. Cross peak intensities in the 2D proton NOESY spectra show a transformation from B-DNA to A-DNA characteristics upon the addition of Co(NH3)6Cl3. The temperature-dependent 59Co transverse and longitudinal relaxation rates demonstrate that Co(NH3)6(3+) is site-bound to the oligomer. Such localization is not a general feature of Co(NH3)6(3+) binding to oligonucleotides. 59Co NMR relaxation and CD measurements demonstrate chiral discrimination by d(CCCCGGGG) for the two stereoisomers of Co(en)3(3+). Both stereoisomers bind tightly as judged by 59Co NMR, and both cause large (but nonequivalent) changes in the CD of this oligomer.

Base Sequence↗
PubMed1993

The Saccharomyces cerevisiae Cdc68 transcription activator is antagonized by San1, a protein implicated in transcriptional silencing.

The CDC68 gene (also called SPT16) encodes a transcription factor for the expression of a diverse set of genes in the budding yeast Saccharomyces cerevisiae. To identify other proteins that are functionally related to the Cdc68 protein, we searched for genetic suppressors of a cdc68 mutation. Four suppressor genes in which mutations reverse the temperature sensitivity imposed by the cdc68-1 mutation were found. We show here that one of the suppressor genes is the previously reported SAN1 gene; san1 mutations were originally identified as suppressors of a sir4 mutation, implicated in the chromatin-mediated transcriptional silencing of the two mating-type loci HML and HMR. Each san1 mutation, including a san1 null allele, reversed all aspects of the cdc68 mutant phenotype. Conversely, increased copy number of the wild-type SAN1 gene lowered the restrictive temperature for the cdc68-1 mutation. Our findings suggest that the San1 protein antagonizes the transcriptional activator function of the Cdc68 protein. The identification of san1 mutations as suppressors of cdc68 mutations suggests a role for Cdc68 in chromatin structure.

Alleles↗
PubMed1993

Staining of endothelial cells and macrophages in atherosclerotic lesions with human heat-shock protein-reactive antisera.

Our previous epidemiological studies have shown that levels of serum antibodies against mycobacterial heat-shock protein (hsp) 65 correlate positively with carotid atherosclerosis in subjects aged 40 to 79 years. To determine whether these high-titer sera also react with homologous human hsp60 and/or cell components of atherosclerotic lesions, we selected 15 human sera samples, each with high or low titers to recombinant mycobacterial hsp65, and investigated their reactivity with human arterial lesion components by immunoblotting and immunofluorescence techniques. All five higher-titer sera against hsp65 reacted with a 60-kDa band of atherosclerotic lesion proteins and human recombinant hsp60 on Western blots. Pooled sera with low antibody titers to hsp65 diluted similarly as high-titer sera did not show reactivity with atherosclerotic lesion and media proteins. By immunohistochemistry and immunofluorescence with human immunoglobulin G isolated from different sera, labeled with biotin, and visualized with a streptavidin conjugate, positive staining was observed in sections of fatty streaks and atherosclerotic plaques of carotid arteries, and weak staining was observed in the normal intima. Double immunofluorescence identified the majority of positively stained cells as macrophages, endothelial cells, and a few smooth muscle cells. In summary, serum antibodies against hsp65 cross-react with the human 60-kDa homologue present in high levels in atherosclerotic lesions and are mainly reacting with macrophages and endothelial cells, supporting our concept of a possible involvement of humoral-mediated immune reaction against hsp60 in atherogenesis.

Aged↗
PubMed1993

Increased expression of heat shock protein 65 coincides with a population of infiltrating T lymphocytes in atherosclerotic lesions of rabbits specifically responding to heat shock protein 65.

We have shown previously that atherosclerotic lesions can be induced in normocholesterolemic rabbits by immunization with mycobacterial heat shock protein 65 (hsp65), which has a high degree of sequence homology with mammalian hsp60. To investigate a possible relationship between hsp60 expression and the antigenic specificities of infiltrating T cells in the lesion, 38 New Zealand White rabbits were treated either by immunization with recombinant mycobacterial hsp65 or by administration of a 0.2% cholesterol diet. Atherosclerotic lesions were observed after 16 wk, particularly in the aortic arch and arterial bifurcations of rabbits immunized with hsp65 or fed with a cholesterol-rich diet. Hsp65 staining of aortas showed a heterogeneous distribution, and significantly increased staining intensity in atherosclerotic lesions compared to aortic media or adventitia. This abundantly expressed hsp65 was observed in atherosclerotic lesions induced by hsp65 immunization as well as those induced by cholesterol-rich diet alone. Interestingly, a population of the T lymphocytes isolated from all forms of atherosclerotic lesions specifically responded to hsp65 in vitro. IL-2-expanded T cell lines derived from atherosclerotic lesions showed a significantly higher hsp65 reactivity than those developed from peripheral blood of the same donor. Furthermore, levels of circulating antibodies and numbers of spleen cells specifically reacting against hsp65 were elevated in all experimental animals. Flow cytometric analysis of spleen cells showed elevated immune response-associated antigen expression in treated animals. In conclusion, increased hsp65 expression in intimal cells and the presence of hsp65-specific T cells in blood and in atherosclerotic lesions may be important in initiating the development of atherosclerosis and perpetuating the lesions.

Animals↗
PubMed1993

Opioid, calcium, and adrenergic receptor involvement in protopine analgesia.

The analgesic effect of protopine (Pro), an alkaloid isolated from Papaveraceae, was confirmed by tail-pinch and hot-plate tests when given sc 10-40 mg.kg-1, and 20-40 mg.kg-1 inhibited the spontaneous movements of mice. Pro 40 mg.kg-1 increased the sleeping rate, prolonged the sleeping duration, and shortened the sleeping latency in mice hypnotized by ip pentobarbital sodium 30 mg.kg-1. Pro 10-40 mg.kg-1 did not affect the inflammatory reaction induced by xylene and egg white. An icv injection of Pro 20-200 micrograms/mouse showed a remarkable analgesic effect in mice. The icv pretreatment of naloxone 2 micrograms blocked the analgesic effect completely. CaCl2 40 micrograms/mouse (ICV) or methotrexate 10 mg.kg-1 (ip), an agonist of Ca2+ channel, showed a complete blockade of the analgesia, while nifedipine 100 mg.kg-1(po), a blocker of Ca2+ channel, enhanced the analgesic effect. The ip pretreatment of reserpine 4 mg.kg-1 reduced the Pro analgesia. Phentolamine 10 mg.kg-1(ip), an alpha-adrenergic blocker, tended to weaken the analgesia, but propranolol 10 mg.kg-1(ip), a beta-blocker, did not affect it. These results suggest that Pro displays its analgesic effect mainly through the opioid and calcium systems and partly through the adrenergic mechanism.

Alkaloids↗
PubMed1993

Immunology of atherosclerosis. Demonstration of heat shock protein 60 expression and T lymphocytes bearing alpha/beta or gamma/delta receptor in human atherosclerotic lesions.

Our previous work revealed the presence of a great number of activated T lymphocytes in early human atherosclerotic lesions, and we were able to induce atherosclerosis in normocholesterolemic rabbits by immunization with Mycobacterium tuberculosis heat-shock protein (HSP) 65. We hypothesized this latter phenomenon to arise from cross-reactivity of mycobacterial HSP 65 with the endogenously expressed homologous 60-kd form of this stress protein. To study HSP 60 expression and the phenotype of intima infiltrating T lymphocytes relative to the T cell receptor (TCR) in human atherosclerotic lesions, specimens of aorta, carotid arteries, and internal mammary arteries and veins, as well as saphenous veins and vena cava from 27 subjects, aged 23 to 80 years, were examined using immunohistochemical and immunofluorescence techniques on serial frozen tissue sections. HSP 60 was detected on endothelium, smooth muscle cells, and/or mononuclear cells of all carotid and aortic specimens, whereas vessels of smaller diameter, serving as reference specimens for normal intima without atherosclerotic lesions and mononuclear infiltration, showed no detectable expression of this stress protein. Furthermore, although the majority of CD3+ cells within the mononuclear cell infiltrates of atherosclerotic lesions bear the alpha/beta TCR, a considerable portion also consisted of gamma/delta TCR+ cells. Thus, 9.7% of T cells in the transition zone between normal intima and fatty streaks carry the gamma/delta TCR, a proportion that decreases to 6.6% and 4.3% in fatty streaks and atherosclerotic plaques, respectively. We conclude that the intensity of HSP 60 expression correlates positively with the atherosclerotic severity and that most lymphocytes participating in atherogenesis bear the alpha/beta TCR, although gamma/delta TCR+ cells are also enriched in atherosclerotic lesions. Expression of HSP 60 by intimal cells, caused, eg, by hemodynamic shear forces, may be responsible for recruitment of HSP-sensitized T cells, thus leading to the induction of an initiating inflammatory process in atherosclerosis. Other risk factors, such as high serum cholesterol levels, contribute to the final outcome of the disease.

Adult↗
PubMed1993

Molecular biology of human papillomavirus.

The papillomavirus is at present considered to be an independent group of viruses, possibly an independent family. Human papillomavirus (HPV) can cause warts of the skin and mucosa, and is now widely recognized as an important etiologic factor of both benign and malignant tumors in the lower genital tract. In this paper the biological properties of HPV, including its genomic organization and the open reading frames, are described; the relationship between HPV and uterine cervical carcinoma, especially in regard to the role of the viral oncogenes E6 and E7, is discussed in detail.

Base Sequence↗
PubMed1992

Structural organization of proteins on the oxidizing side of photosystem II. Two molecules of the 33-kDa manganese-stabilizing proteins per reaction center.

The 33-kDa manganese-stabilizing protein stabilizes the manganese cluster in the oxygen-evolving complex. There has been, however, a considerable amount of controversy concerning the stoichiometry of this photosystem II (PS II) component. In this paper, we have verified the extinction coefficient of the manganese-stabilizing protein by amino acid analysis, determined the manganese content of oxygen-evolving photosystem II membranes and reaction center complex using inductively coupled plasma spectrometry, and determined immunologically the amount of the manganese-stabilizing protein associated with photosystem II. Oxygen-evolving photosystem II membranes and reaction center complex preparations contained 258 +/- 11 and 67 +/- 3 chlorophyll, respectively, per tetranuclear manganese cluster. Immunoquantification of the manganese-stabilizing protein using mouse polyclonal antibodies on "Western blots" demonstrated the presence of 2.1 +/- 0.2 and 2.0 +/- 0.3 molecules of the manganese-stabilizing protein/tetranuclear manganese cluster in oxygen-evolving PS II membranes and highly purified PS II reaction center complex, respectively. Since the manganese-stabilizing protein co-migrated with the D2 protein in our electrophoretic system, accurate immunoquantification required the inclusion of CaCl2-washed PS II membrane proteins or reaction center complex proteins in the manganese-stabilizing protein standards to compensate for the possible masking effect of the D2 protein on the binding of the manganese-stabilizing protein to Immobilon-P membranes. Failure to include these additional protein components in the manganese-stabilizing protein standards leads to a marked underestimation of the amount of the manganese-stabilizing protein associated with these photosystem II preparations.

Chloroplasts↗
PubMed1992

Synthesis and characterization of N-methyliminodiacetato trans-R,R-, trans-S,S-, and cis-1,2-diaminocyclohexane platinum (IV) complexes: crystal structure of chloro(trans-R,R-1,2-diaminocyclohexane) (N-methyliminodiacetato) platinum(IV) chloride.

The compounds, chloro(trans-R,R-1,2-diaminocyclohexane) (N-methyliminodiacetato)platinum(IV) chloride, chloro(trans-S,S-1,2-diaminocyclohexane)(N-methyliminodiacetato) platinum(IV) chloride, and chloro(cis-1,2-diaminocyclohexane)(N-methyliminodiacetato)platinum (IV) chloride, were prepared and characterized by elemental analysis, IR, and 195Pt NMR. The crystal structure of one of these three compounds, chloro(trans-R,R-1,2-diaminocyclohexane) (N-methyliminodiacetato) platinum(IV) chloride, was determined by x-ray single crystal diffraction. This compound is particularly interesting because the 1,2-diaminocyclohexane (DACH) ring is in a twist-boat configuration rather than the chair configuration previously reported for other DACH platinum compounds. The crystal structure consists of two independent cations and anions, with all atoms between these two independent molecules (except those in the chiral DACH) related by a pseudo-inversion center. Both platinum atoms have slightly distorted octahedral coordination, with angles ranging from 81.8 to 100.8 degrees. Crystallographic details: space group P2(1) (monoclinic); a = 19.864(5) A, b = 7.026(2) A, c = 12.446(3) A, beta = 106.64(2) degrees; Z = 4; R = 0.036 for 2333 reflections.

Cyclohexanes↗
PubMed1992

A high-density-lipoprotein receptor appears to mediate the transfer of essential fatty acids from high-density lipoprotein to lymphocytes.

It has been shown previously that a specific high-density lipoprotein (HDL) receptor exists on human lymphocytes that recognizes apoprotein (apo) A1 as its ligand, and may be responsible for utilization of HDL lipids to respond optimally to mitogenic stimulation when cultured in serum-free medium supplemented with HDL. To clarify further the relationship between various HDL lipids used by lymphocytes and HDL receptor activity, the lipid composition of the cells and the regulation of HDL and low-density lipoprotein (LDL) receptors on freshly isolated lymphocytes and mitogen-activated T-blasts after treatment with lipoproteins, liposomes or fatty acids were investigated. Our data show that the linear increase in cell proliferation correlates with the presence of HDL in fatty-acid-free culture medium in the concentration range of HDL receptor saturation. Decreased binding/uptake of dioctadecylindocarbocyanine (DiI)-fluorescence-labelled HDL by freshly isolated lymphocytes was observed in the presence of unlabelled HDL in 4-day culture, whereas T-blast binding/uptake was down-regulated by preincubation not only with HDL but also with LDL. T-blasts pretreated with HDL showed increased cellular contents of phosphatidylcholine, oleic acid (C18:1,n-9) and linoleic acid (C18:2,n-6), which are essential for optimal proliferation of mitogen-stimulated lymphocytes. Furthermore, DiI-HDL binding on lymphocytes was down-regulated by up to 20% (resting T cells) and 50% (T-blasts) when cultured in the presence of apoA1-phosphatidylcholine liposomes (T-blasts only), oleic acid or linoleic acid, but not by stearic acid (C18:0). The results indicate that HDL provide lymphocytes with essential fatty acids, which in turn regulate HDL receptor activity.

Adult↗
PubMed1992

Lipid utilization by human lymphocytes is correlated with high-density-lipoprotein binding site activity.

The nature and physiological importance of high-density lipoprotein (HDL) binding sites on unstimulated (resting) and mitogen-activated (blast) human peripheral blood lymphocytes were investigated. Specific HDL binding on resting and blast T-lymphocytes was saturable at 50 micrograms of 125I-HDL/ml and of high affinity, with Kd values of 8.1 x 10(-8) M and 6.5 x 10(-8) M, respectively, and Bmax. values of 79 ng and 180 ng/mg of cell protein respectively at 4 degrees C. Binding of HDL double-labelled with fluorescent dioctadecylindocarbocyanine (Dil) and isotope (125I) as well as of single fluorescence- or isotope-labelled HDL was inhibited competitively by HDL apoproteins. Studies of the cholesterol flux between the cells and HDL showed that HDL, low-density lipoprotein (LDL) or BSA at a concentration of 100 micrograms/ml in the tissue culture medium did not result in a significant difference in exogenous [3H]cholesterol efflux from the cell membrane at 37 degrees C. Proliferating T-blasts incorporated more cholesterol from HDL or LDL than did resting lymphocytes. When the cells were pulsed with 125I-HDL and chased in fresh lipid-free medium, up to 80% of the radioactivity released was not precipitable with trichloroacetic acid. This percentage decreased in a competitive manner when unlabelled HDL was present in the chase incubation medium. Finally, cultivation of lymphocytes with conditioned medium from macrophages increased Dil-HDL binding/uptake, while it was decreased by mevinolin-induced inhibition of hydroxymethylglutaryl-coA reductase. In conclusion, human lymphocytes possess a HDL binding site (receptor) responsible for lipid binding/uptake and concomitant internalization and degradation of apoproteins from HDL, but not for reverse cell membrane cholesterol transport. The activity of the binding site is up-regulated during cell proliferation and down-regulated during cell growth suppression.

Adult↗
PubMed1992

Leukocyte chemotactic activity of cyclophilin.

During the purification of eosinophil chemotactic factors synthesized by the uterus in response to estrogen we isolated a protein having an N-terminal (15 amino acids) sequence identical to that of rat cyclophilin. Our data demonstrate that cyclophilin, a cytosolic protein isolated from bovine thymocytes, which specifically binds the immunosuppressive drug cyclosporin A, as well as recombinant human cyclophilin, displays eosinophil chemotactic activity. In addition to its chemotactic activity, cyclophilin stimulated the release of peroxidase activity from eosinophils. Maximal chemotactic activity of cyclophilin was achieved at a concentration of approximately 10 nM. At similar concentrations cyclophilin was also able to stimulate the migration of neutrophils. This chemotactic activity could be prevented by the addition of cyclosporin A, but not by a nonimmunosuppressive analog (1-fur-furyl-cyclosporin A) at similar concentrations. This chemotactic activity may represent an additional mechanism by which immunosuppressive drugs function to prevent tissue rejection.

Amino Acid Isomerases↗
PubMed1992

Dependency on the brain function of arginine vasopressin system of the development to and recovery from analgesic tolerance to morphine.

Concomitant intracerebroventricular (i.c.v.) injection of anti-arginine vasopressin (AVP) antiserum dose-dependently suppressed the development of analgesic tolerance to daily morphine, 10 mg/kg, s.c., in mice. This suppressive effect of the antiserum was reduced by incubating the antiserum with AVP in vitro, before i.c.v. injection, suggesting that the antiserum inactivates brain AVP to result in the suppression of the development of tolerance in vivo. Similar to the antiserum, both AVP V1 and V2 antagonists given i.c.v., 10 ng and 20 ng/mouse, respectively, suppressed the development of morphine tolerance. Meanwhile, the administration of antiserum dose-dependently recovered morphine analgesia in morphine-tolerant mice and a complete recovery of analgesia was observed at the highest dose of antiserum following the second injection, and the effect of antiserum was maintained for 3 days after its withdrawal. Likewise, 10-100 ng/mouse of AVP V1 receptor antagonist given i.c.v. recovered morphine analgesia partially but significantly in a dose-dependent manner; however, AVP V2 receptor antagonist at the same doses partially recovered analgesic effect but the effect was neither significant nor dose-dependent. These findings suggest that the tolerance developed to morphine can be reversible when disturbing the function of brain AVP, but in addition to the different mechanisms of antiserum, V1 and V2 receptor antagonists, the V1 receptor-mediated mechanism may be more closely concerned in this phenomenon.

Angiotensin Receptor Antagonists↗