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Biomedical subjects

Z Ye

Publications and source records attributed to Z Ye.

At least 109 records · Page 6Linked to original sources

Molecular epidemiology of hepatitis B virus vaccine variants in Singapore.

Perinatal infection with variants of hepatitis B virus occurs despite combined immunoprophylaxis with hepatitis B immunoglobulin and currently licensed plasma-derived and recombinant yeast hepatitis B vaccines. Several variants have been detected during a large study of infants born to carrier mothers in Singapore. The most frequent variant was a virus in which a single amino acid substitution Gly to Arg occurred at amino acid position 145 of the outer protein coat of the virus. Similar mutations have been described in Italy, Japan, the USA and a number of other countries. The emergence of antibody escape mutants is a cause for concern for the detection of virus and possibly for future immunization programmes.

Amino Acids↗

Combined oral contraceptives and risk of cervical carcinoma in situ. WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

BACKGROUND: Although the possible influence of oral contraceptives on risk of cervical carcinoma in situ has been the subject of multiple prior investigations, the results have been inconsistent. METHODS: Data from a multinational, collaborative case-control study were analysed to investigate further this possible relationship. To assess potential screening bias, some statistical analyses were restricted to subgroups of cases with and without symptoms at the time of their diagnosis. RESULTS: Relative risk estimates in relation to various features of oral contraceptive use tended to be highest for asymptomatic disease, lowest for disease presenting with vaginal bleeding, and intermediate for disease presenting with other symptoms, suggesting the presence of a screening bias. In women with vaginal bleeding, who are least likely to have been detected by routine screening, no elevated risk of cervical carcinoma in situ was observed in relation to ever having used combined oral contraceptives, but there was an increased risk in users of over 60 months' duration. An increasing trend in risk with duration of use was most pronounced in these women who first used oral contraceptives in the past 5-10 years; and in women who used oral contraceptives for more than 60 months, risk declined with time since last use. CONCLUSION: These findings could reflect a reversible effect of long-term use of oral contraceptives at an intermediate stage in the carcinogenic process, or a non-causal relationship due to unidentified sources of bias or confounding.

Adult↗

Nucleus-targeting domain of the matrix protein (M1) of influenza virus.

The matrix protein M1 of influenza virus A/WSN/33 was shown by immunofluorescent staining to be transported into the nuclei of transfected cells without requiring other viral proteins. We postulated the existence of a potential signal sequence at amino acids 101 to 105 (RKLKR) that is required for nuclear localization of the M1 protein. When CV1 cells were transfected with recombinant vectors expressing the entire M1 protein (amino acids 1 to 252) or just the first 112 N-terminal amino acids, both the complete M1 protein and the truncated M1 protein were transported to the nucleus. In contrast, expression in CV1 cells of vectors coding for M1 proteins with deletions from amino acids 77 to 202 or amino acids 1 to 134 resulted only in cytoplasmic immunofluorescent staining of these truncated M1 proteins without protein being transported to the nucleus. Moreover, no nuclear membrane translocation occurred when CV1 cells were transfected with recombinant vectors expressing M1 proteins with deletions of amino acids 101 to 105 or with substitution at amino acids 101 to 105 of SNLNS for RKLKR. Furthermore, a synthetic oligopeptide corresponding to M1 protein amino acids 90 to 108 was also transported into isolated nuclei derived from CV1 cells, whereas oligopeptides corresponding to amino acid sequences 25 to 40, 67 to 81, and 135 to 164 were not transported into the isolated cell nuclei. These data suggest that the amino acid sequence 101RKLKR105 is the nuclear localization signal of the M1 protein.

Amino Acid Sequence↗

Membrane vesiculation function and exocytosis of wild-type and mutant matrix proteins of vesicular stomatitis virus.

Transfection of mammalian CV1 cells with a recombinant M-gene pTM1 plasmid, driven by vaccinia virus-expressed phage T7 polymerase, resulted in the expression of matrix (M) protein, which is progressively released from the exterior surface of the transfected-cell plasma membrane. Exocytosis of M protein begins 2 to 4 h posttransfection and reaches a peak by 10 to 16 h posttransfection; dye uptake studies reveal that > 97% of cells are alive and have intact membranes at 16 h posttransfection. Density gradient centrifugation and labeling with radioactive palmitic acid revealed that the M protein is released from cells in association with lipid vesicles. Expression of M-gene deletion mutants suggests that exocytosis of M protein requires the presence of a membrane-binding site at N-terminal amino acids 1 to 50. Cells transfected with the pTM1 plasmid containing the M gene of the temperature-sensitive mutant tsO23 expressed ample quantities of the mutant M protein at permissive (31 degrees C) and restrictive (39 degrees C) temperatures, but the exocytosis of the mutant M protein occurred only at the permissive temperature. The tsO23 M gene has three site-specific mutations resulting in amino acid substitutions at residues 21, 111, and 227. Expression of wild-type and mutant M genes with mutations or revertants at each of these sites resulted in exocytosis of M protein at the nonpermissive temperature only when wild-type leucine was present at residue 111, but M-protein exocytosis was restricted (to some extent even at the permissive temperature) when mutant phenylalanine was present at residue 111. Past and present data indicate that a specific structural conformation of the M protein is responsible for the formation and budding of vesicles, a property of the M protein which probably also promotes vesicular stomatitis virus assembly and budding of virions from host cells.

Amino Acid Sequence↗

A case of malignant melanoma: disease progression correlated with serum levels of 5-S-Cysteinyldopa (5-S-CD) and intercellular adhesion molecule-1 (ICAM-1).

A 36-year-old Japanese female, in whom malignant melanoma was detected from symptoms of brain metastasis, died 7 months later. The serum levels of 5-S-Cysteinyldopa (5-S-CD) and intercellular adhesion molecule-1 (ICAM-1) correlated with the disease progression. These values may be useful markers of disease progression for malignant melanoma, because the material is easily, frequently, and non-invasively obtained at regular intervals.

Adult↗

Prostaglandins mediate the stimulatory effects of endothelin-1 on cAMP accumulation and inositol-1,4,5-trisphosphate production and contraction in cat iris sphincter.

We previously reported that in the iris sphincter smooth muscle, endothelin-1 (ET-1) activates both adenylyl cyclase and the phosphoinositide cascade and that the changes in the levels of cAMP and inositol-1,4,5-trisphosphate (IP3) produced are species specific. In the present study, we examined the mechanism of the ET-1 effects in cat iris sphincter. In general, we found that ET-1 (0.1 microM) increased prostaglandin E2 (PGE2) release by 156%, cAMP accumulation by 310%, IP3 production by 88% and induced contraction; that PGE2 increased cAMP accumulation, IP3 production and contraction; and that the effects of ET-1 are inhibited by indomethacin (Indo), suggesting that arachidonic acid metabolites may mediate the responses to the peptide. Kinetic studies revealed the following: (1) The effect of ET-1 on cAMP accumulation is rapid (within 30 sec), dose dependent (EC50 = 5.8 nM) and completely abolished by Indo (Ki = 0.16 microM), a cyclooxygenase inhibitor, but not by nordihydroguairetic acid, a lipoxygenase inhibitor, implying the involvement of PGs. (2) ET-1 dose-dependently evoked PGe2 release (EC50 = 1.8 nM), IP3 production (EC50 = 4.5 nM) and contraction (EC50 = 5 nM) and that all of these responses were inhibited by Indo. (3) PGE2 increased cAMP accumulation in a dose-dependent manner with an EC50 of 1.5 x 10(-7) M, and PGD2 and PGF2 alpha had little effect on the cyclic nucleotide. (4) PGE2 (1 microM), increased IP3 production by 55% and induced muscle contraction in a dose-dependent manner (EC50 = 40 nM). We conclude from these data that in cat iris sphincter PGs may mediate ET-1-induced cAMP accumulation, IP3 production and smooth muscle contraction.

Adenylyl Cyclases↗

[Method of designing a mold for processing corneal lenticules in epikeratophakia with excimer laser].

PURPOSE: To design a mold for processing optical power in epikeratophakia. METHOD: With excimer laser a corneal graft with appropriate optical power shall be got on the formula of the mold's radius curvature. RESULTS: Based upon the formula from the data, a 12D mold was accomplished to obtain a suitable cornea lens for epikeratophakia. CONCLUSION: The 12D mold presents the value to some extent in processing the desired optical power of corneal graft for those patients requiring epikeratophakia.

Epikeratophakia↗

Tissue printing.

An image of the tissue distribution of specific mRNAs, proteins, enzymes, or antigens is conveniently obtained by "printing" the cut surface of a tissue section onto a suitable substrate film and developing the film with appropriate reagents. It is also possible to localize metabolites by tissue printing. Most plant tissues leave a physical print/impression with detailed anatomical information. Epidermal surfaces of growing organs can be printed without damaging the organ. We provide this review to encourage further use and further development of these convenient and helpful procedures.

Enzymes↗

Two different mutations in codon 68 are observed in Hb G-Philadelphia heterozygotes.

Through sequencing of amplified DNA containing the appropriate alpha-globin genes we have identified the base substitution leading to the formation of Hb G-Philadelphia [alpha 68(E17)Asn Lys]. Three subjects (approximately 25% Hb G) had an ACC AAA change at codon 68 of the alpha 2-globin gene; the chromosome with this mutation carried two alpha genes (alpha alpha). Six subjects (approximately 33% Hb G) had an AAC AAG change at the same codon of the alpha 2 alpha 1 hybrid gene on a chromosome with the 3.7 kb deletion (-alpha 3.7). These results indicate two independent mutations which likely occurred in different populations; increase in the level of Hb G is primarily dependent upon the loss of one or more alpha-globin genes.

Adult↗

Clonal analysis of human astrocytomas.

Clonal analysis of many human cancers have generally confirmed that they are monoclonal. Although astrocytic neoplasms are the most frequently occurring primary tumors in the central nervous system, their clonal composition has not been systematically studied. In this report, the clonal composition of 22 human astrocytomas of all histological grades (2 well-differentiated astrocytomas, 3 anaplastic astrocytomas and 17 glioblastoma multiforme) was determined by analysis of the pattern of X-chromosome inactivation. Leukocyte and non-tumor brain DNA were used as controls. In addition, specimens from different parts of four glioblastoma multiforme were analyzed to determine whether remote areas of the same tumor had the same clonal composition. Eighteen of nineteen informative astrocytomas had a monoclonal pattern of X-chromosome inactivation; one glioblastoma multiforme had loss of heterozygosity on the X chromosome. Specimens from different areas of the same tumor all had identical patterns of X-chromosome inactivation. Leukocytes and non-tumor brain used as controls uniformly had a polyclonal pattern of X-chromosome inactivation. Furthermore, loss of heterozygosity for chromosomes 10 or 17 p loci was found in 64% (9/14) of informative specimens and identical allelic patterns were observed in specimens from different areas of the same tumor. Our results demonstrate that human astrocytomas from low to high-grade are characterized by monoclonal cell populations. The presence of monoclonality in even low-grade neoplasms suggests that in astrocytic tumors the establishment of monoclonality occurs quite early. Also, the finding of a monoclonal pattern in intermediate- and high-grade astrocytomas further supports the hypothesis that clonal expansion underlies astrocytic tumor progression.

Adult↗

The inhibition of silica-induced lung inflammation by dexamethasone as measured by bronchoalveolar lavage fluid parameters and peroxynitrite-dependent chemiluminescence.

The inhalation of silica has been shown to produce a dramatic inflammatory and toxic response within the lungs of humans and laboratory animals. Currently, no effective treatment exists for workers who may have been exposed to the inhalation of silica. The objective of this study was to develop an animal model in which we could evaluate the effect that anti-inflammatory steroids have on the acute silica-induced pulmonary inflammatory response. Male Fischer 344 rats were pretreated with either dexamethasone (2 mg/kg) or saline vehicle (i.p.) on days 1, 3, and 5. On day 6, the animals from the two groups were then intratracheally instilled with either silica (20 mg/0.5 ml saline vehicle) or saline vehicle (0.5 ml). Twenty-four hours after the instillations in the non-steroid group, significant increases occurred in total protein, total number of cells, neutrophils, and lymphocytes recovered from the lungs of animals treated with silica compared to saline controls. Silica also caused dramatic increases in the luminol-dependent chemiluminescence (LDCL) of lung tissue and bronchoalveolar lavage (BAL) cells. The LDCL reaction was markedly decreased by either superoxide dismutase (SOD) or N-nitro-L-arginine methyl ester hydrochloride (L-NAME). SOD is involved in the enzymatic breakdown of superoxide anion, while L-NAME, a nitric oxide (NO) synthase inhibitor, prevents the formation of NO. When the superoxide anion and NO react, they form the highly oxidizing substance peroxynitrite. This study then implicates peroxynitrite as an agent which may be involved in the silica-induced oxidant lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Interaction of artemisinin and tetracycline or erythromycin against Plasmodium falciparum in vitro.

Antimalarial activities of tetracycline (TC) and erythromycin (EM), alone or in combination with artemisinin (Qinghaosu, QHS), were studied using chloroquine (CQ)-sensitive (D6) and -resistant (W2) strains of Plasmodium falciparum in vitro. The antimalarial potency of TC (IC50 = 9862 nM for the CQ-sensitive parasite, 32414 nM for the CQ-resistant one) or EM (IC50 = 45787 nM for the CQ-sensitive parasite, 33397 nM for the CQ-resistant one) was much less than that of QHS (IC50 ranging from 25 to 40 nM). The CQ-resistant falciparum parasite displayed a cross-resistance to TC, while both the drug-sensitive and -resistant parasites exhibited similar responses to EM. However, antimalarial potency of EM appeared to be less than that of TC against the drug-sensitive parasite. When TC was combined with QHS, an additive interaction was observed against the CQ-sensitive falciparum parasite, while synergism was found with the CQ-resistant parasite. When EM was tested in combination with QHS, a potentiating interaction occurred with both the CQ-sensitive and resistant falciparum parasite. The above results indicated that the QHS combination with either TC or EM may be a promising antimalarial preparation with low recrudescence compared to artemisinin used alone in clinical practice.

Animals↗

The brachioradialis forearm flap: anatomy and clinical application.

The blood supply to the brachioradialis muscle and the skin of the forearm was studied in latex-injected arms. The dominant perforator to the muscle arose from the brachial artery (27.3 percent), radial recurrent artery (33.3 percent), or radial artery (39.4 percent). In all cases, adequate perforators exist from the radial artery so that transfer as either a muscle or musculocutaneous free flap based on this vessel is possible. In 10 arms the septocutaneous perforators from the radial artery were dissected to determine the relationship between the forearm and brachioradialis flaps. Transfer of the brachioradialis muscle as a free flap or combined with the radial artery forearm flap based on the radial artery and either the venae comitantes and/or the cutaneous veins is feasible. Four clinical cases demonstrate the usefulness of this flap.

Adult↗

Possible factors influencing the haemoglobin and fetal haemoglobin levels in patients with beta-thalassaemia due to a homozygosity for the IVS-I-6 (T-->C) mutation.

We have collected haematological, haemoglobin (Hb) and DNA sequence data for 29 patients with a homozygosity for the IVS-I-6 (T-->C) mutation with the intention of identifying factors contributing to the observed variability in the severity of the disease. None of the patients had received blood transfusion therapy for at least 6 months prior to the study. Hb levels varied from 5.0 to 9.9 g/dl. Patients with high Hb F (more than 1.5 g/dl or > 20%) had high total Hb levels (7.5-9.7 g/dl) but some with low Hb F also had high total Hb levels; two had a concomitant alpha-thalassaemia-2 (alpha-thal-2) heterozygosity. An inverse correlation between the Hb F and Hb A2 levels was observed. The majority of the patients were homozygous for haplotype VI (49/58 chromosomes) but haplotypes IV (2/58) and VII (7/58) were also present. The only haplotype IV homozygote had high Hb F levels with high G gamma values and the C-->T mutation at position -158 in the G gamma promoter, while both high and low Hb F levels were observed among patients with haplotypes VI and VII. Analysis of sequence variations in regulatory regions included the 5' hypersensitive sites (HS) 4. 3 and 2 of the locus control region (LCR), the G gamma and A gamma 5' flanking regions, the second intervening sequence (IVS-II), and the 5' beta-globin gene region in two patients with high Hb F (one homozygote each for haplotypes VI and IV), and in two patients with low Hb F levels (one homozygote each for haplotypes VI and VII). Haplotype specific differences were observed in the LCR 5' HS-2 and in the G gamma and A gamma flanking and IVS-II regions; however, no differences were present between the low and high Hb F-producing haplotype VI chromosomes, suggesting a major role for factors which are not linked to the beta-globin gene cluster in mediating gamma-globin gene expression in patients with this type of beta-thal.

Adolescent↗

Membrane-binding domains and cytopathogenesis of the matrix protein of vesicular stomatitis virus.

The membrane-binding affinity of the matrix (M) protein of vesicular stomatitis virus (VSV) was examined by comparing the cellular distribution of wild-type (wt) virus M protein with that of temperature-sensitive (ts) and deletion mutants probed by indirect fluorescent-antibody staining and fractionation of infected or plasmid-transfected CV1 cells. The M-gene mutant tsO23 caused cytopathic rounding of cells infected at permissive temperature but not of cells at the nonpermissive temperature; wt VSV also causes rounding, which prohibits study of M protein distribution by fluorescent-antibody staining. Little or no M protein can be detected in the plasma membrane of cells infected with tsO23 at the nonpermissive temperature, whereas approximately 20% of the M protein colocalized with the membrane fraction of cells infected with tsO23 at the permissive temperature. Cells transfected with a plasmid expressing intact 229-amino-acid wt M protein (M1-229) exhibited cytopathic cell rounding and actin filament dissolution, whereas cells retained normal polygonal morphology and actin filaments when transfected with plasmids expressing M proteins truncated to the first 74 N-terminal amino acids (M1-74) or deleted of the first 50 amino acids (M51-229) or amino acids 1 to 50 and 75 to 106 (M51-74/107-229). Truncated proteins M1-74 and M51-229 were readily detectable in the plasma membrane and cytosol of transfected cells as determined by both fluorescent-antibody staining and cell fractionation, as was the plasmid-expressed intact wt M protein. However, the expressed doubly deleted protein M51-74/107-229 could not be detected in plasma membrane by fluorescent-antibody staining or by cell fractionation, suggesting the presence of two membrane-binding sites spanning the region of amino acids 1 to 50 and amino acids 75 to 106 of the VSV M protein. These in vivo data were confirmed by an in vitro binding assay in which intact M protein and its deletion mutants were reconstituted in high- or low-ionic-strength buffers with synthetic membranes in the form of sonicated unilammelar vesicles. The results of these experiments appear to confirm the presence of two membrane-binding sites on the VSV M protein, one binding peripherally by electrostatic forces at the highly charged NH2 terminus and the other stably binding membrane integration of hydrophobic amino acids and located by a hydropathy plot between amino acids 88 and 119.

1,2-Dipalmitoylphosphatidylcholine↗

Cell-free assembly of the herpes simplex virus capsid.

Herpes simplex virus type 1 (HSV-1) capsids were found to assemble spontaneously in a cell-free system consisting of extracts prepared from insect cells that had been infected with recombinant baculoviruses coding for HSV-1 capsid proteins. The capsids formed in this system resembled native HSV-1 capsids in morphology as judged by electron microscopy, in sedimentation rate on sucrose density gradients, in protein composition, and in their ability to react with antibodies specific for the HSV-1 major capsid protein, VP5. Optimal capsid assembly required the presence of extracts containing capsid proteins VP5, VP19, VP23, VP22a, and the maturational protease (product of the UL26 gene). Assembly was more efficient at 27 degrees C than at 4 degrees C. The availability of a cell-free assay for HSV-1 capsid formation will be of help in identifying the morphogenetic steps that occur during capsid assembly in vivo and in evaluating candidate antiherpes therapeutics directed at capsid assembly.

Capsid↗

Introduction of luminol-dependent chemiluminescence as a method to study silica inflammation in the tissue and phagocytic cells of rat lung.

The inhalation of silica has been shown to produce a dramatic inflammatory and toxic response within the lungs of humans and laboratory animals. A variety of cellular and biochemical parameters are used to assess the silica-induced lung injury. The purpose of this paper is to introduce the use of luminol-dependent chemiluminescence as a new method to study inflammation in both phagocytic cells and lung tissue recovered from silica-exposed animals. Chemiluminescence, or the emission of light, accompanies the release of reactive forms of oxygen when phagocytic cells are challenged. In this study, male Fischer 344 rats were intratracheally instilled with either silica (10 mg/100 g bw) or saline vehicle. One day after the instillations, a marked increase in the chemiluminescence was observed in the lung tissue and bronchoalveolar lavage cells recovered from the silica-treated animals when compared with the saline controls. The light reaction was markedly decreased by either superoxide dismutase of N-nitro-arginine methyl ester hydrochloride. Superoxide dismutase is involved in the enzymatic breakdown of superoxide anion, while N-nitro-L-arginine methyl ester hydrocholoride, a nitric oxide synthase inhibitor, prevents the formation of nitric oxide. When superoxide anion and nitric oxide react, they form the highly oxidizing substance peroxynitrite. This study then implicates peroxynitrite as an agent that may be responsible for some of the oxidant lung injury that is associated with silica exposure. The use of luminol-dependent chemiluminescence may prove valuable as a method to measure the earliest events in the inflammatory process, and may be an adjunct in studying the mechanisms that produce inflammation.

Animals↗