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Biomedical subjects

Lin Liu

Publications and source records attributed to Lin Liu.

At least 37 records · Page 2Linked to original sources
PubMed2003

Ultrastructure of type II alveolar epithelial cells in rats with acute respiratory distress syndrome.

OBJECTIVE: To observe the ultrastructure of type II alveolar epithelium cells of rats with experimental acute respiratory distress syndrome (ARDS). METHODS: Rat models of ARDS were established via oleic acid injection, and the type II alveolar epithelium was isolated and purified to observe the changes in the ultrastructure of the cells under transmission electron microscope. RESULTS: Observation under transmission electron microscope revealed evidently decreased lamellar bodies in type II alveolar epithelial cells leading to vacuolation in rats with ARDS. CONCLUSION: After proper isolation and purification, the morphological changes in type II alveolar epithelial cells can be more easily observed, and the changes in the lamellar bodies suggest that type II cells play an important role in ARDS.

Animals↗
PubMed2003

Effect of Zn7-metallothionein on oxidative stress in liver of rats with severe thermal injury.

AIM: Using the model of burned animal with delayed resuscitation to study antagonistic effect of Zn7-metallothionein (Zn7-MT) on oxidative stress in the liver of rats suffered from severe thermal injury on skin. METHODS: To compare the changes in antioxidant concentrations and antioxidative enzyme activities in the liver or plasma of burned rats with or without Zn7-MT in resuscitation fluid by biochemical assay. RESULTS: After injury, glutathione concentration was progressively decreased with time. At 24 h after injury, activities of glutathione reductase and glutathione peroxidase in the liver of burned rats were increased and then decreased at 48 h postburn. Alpha-tocopherol in plasma was reduced at 24 h and malondialdehyde in the liver was increased significantly postburn. MT and MT-1 mRNA expression in burned rats were activated. Taken together, oxidative stress in the liver of burned rats occurred. Exogenous Zn7-MT attenuated the changes in antioxidant concentrations and antioxidative enzyme activities in the liver or plasma of burned rats. The effect of Zn7-MT was in a concentration-dependent manner and the concentration of 10 micromol/L was the most effective. Exogenous Zn7-MT also inhibited MT-1 mRNA overexpression and increased MT protein concentration. CONCLUSION: Zn7-MT effectively antagonized oxidative stress in the liver of rats with severe thermal injury.

Animals↗
PubMed2003

[Associations of Rsa I polymorphism at the 5' flanking region of CYP2E1 and PON2 148 polymorphism in neonates with preterm delivery].

The objective is to investigate whether Rsa I polymorphism at the 5' flanking region of cytochrome P450 2E1 gene (CYP2E1) and paraoxonase 2 gene polymorphism (PON2 148) in neonates are associated with preterm delivery. Using standard questionnaires, 209 singleton live born mother-neonate pairs (include preterm cases and term controls) were investigated by the trained field workers with cross-sectional survey at the hospitals in Anqing, Anhui Province, China. Epidemiological and clinical data and blood samples were obtained from 209 mother-neonate pairs. CYP2E1 homozygous wild-type (+/+) is not associated with a shortened gestation among neonates, compared with CYP2E1 homozygous mutant-type (-/-)/CYP2E1 heterozygote (+/-) before and after adjustment confounders, however, PON2 Ala148Ala homozygote is significantly associated with a shortened gestation among neonates. When Rsa I polymorphism at the 5' flanking region of CYP2E1 and PON2 148 polymorphism were considered jointly, a significant shortened gestation was observed among neonates with the combined genotype of CYP2E1 homozygous wild-type and PON2 Ala148Ala homozygote. In conclusion, Rsa I polymorphism at the 5' flanking region of CYP2E1 in neonates is not associated with preterm delivery, however, PON2 148 polymorphism in neonates is significantly associated with preterm delivery. Furthermore, the gene interaction between Rsa I polymorphism at the 5' flanking region of CYP2E1 and PON2 148 polymorphism in neonates is significantly associated with preterm delivery.

5' Flanking Region↗
PubMed2002

Direct synthesis of uniform hollow carbon spheres by a self-assembly template approach.

Hollow carbon spheres (50-100 nm) have been synthesized by a self-assembly approach using hexachlorobenzene and Na. NaCl which generated during the reaction has been successfully exploited as a template for the direct synthesis of porous carbon materials, which can be subsequently removed from carbon product by annealing above 1400 degrees C.

Journal Article↗
PubMed2002

An essential role for functional telomeres in mouse germ cells during fertilization and early development.

Late generations of telomerase-null (TR(-/-)) mice exhibit progressive defects in highly proliferative tissues and organs and decreased fertility, ultimately leading to sterility. To determine effects of telomerase deficiency on germ cells, we investigated the cleavage and preimplantation development of embryos derived from both in vivo and in vitro fertilization of TR(-/-) or wild-type (TR(+/+)) sperm with either TR(-/-) or TR(+/+) oocytes. Consistently, fertilization of TR(-/-) oocytes with either TR(+/+) or TR(-/-) sperm, and TR(-/-) sperm with TR(+/+) oocytes, resulted in aberrant cleavage and development, in contrast to the normal cleavage and development of TR(+/+) oocytes fertilized by TR(+/+) sperm. Many (>50%) of the fertilized TR(-/-) eggs developed only one pronucleus, coincident with increased incidence of cytofragmentation, in contrast to the normal formation of two pronuclei and equal cleavage of wild-type embryos. These results suggest that both TR(-/-) sperm and oocytes contribute to defective fertilization and cleavage. We further found that a subset (7-9%) of telomeres was undetectable at the ends of some metaphase I chromosomes from TR(-/-) spermatocytes and oocytes, indicating that meiotic germ cells lacking telomerase ultimately resulted in telomere shortening and loss. Dysfunction of meiotic telomeres may contribute to aberrant fertilization of gametes and lead to abnormal cleavage of embryos, implying an important role of functional telomeres for germ cells undergoing fertilization and early cleavage development.

Animals↗
PubMed2002

Structural elements that govern the substrate specificity of the clot-dissolving enzyme plasmin.

There is remarkable homology between the core structures of plasmin, a fibrin clot-degrading enzyme, and factor D, a complement-activating enzyme, despite markedly different biological functions. We postulated that sequence divergence in the loop structures between these two enzymes mediated the unique substrate and inhibitor interactions of plasmin. Recombinant microplasminogens chimerized with factor D sequences at loops 3, 5, and 7 were cleaved by the plasminogen activator urokinase and developed titratable active sites. Chimerization abolished functional interactions with the plasminogen activator streptokinase but did not block complex formation. The microplasmin chimeras showed enhanced resistance (k(i) decreased up to two to three times) to inactivation of microplasmin by alpha(2)-antiplasmin. Microplasmin chimerization had minimal ( approximately 2 fold) effects on the catalytic efficiency for cleavage of small substrates and did not alter the cleavage of fibrin. However, microplasmin and the microplasmin chimeras showed enhanced abilities to degrade fibrin in plasma clots suspended in human plasma. These studies indicate that loop regions of the protease domain of plasmin are important for interactions with substrates, regulatory molecules, and inhibitors. Because modification of these regions affected substrate and inhibitor interactions, loop chimerization may hold promise for improving the clot dissolving properties of this enzyme.

Binding Sites↗
PubMed2002

Chimerism reveals a role for the streptokinase Beta -domain in nonproteolytic active site formation, substrate, and inhibitor interactions.

Streptokinase (SK) and staphylokinase form cofactor-enzyme complexes that promote the degradation of fibrin thrombi by activating human plasminogen. The unique abilities of streptokinase to nonproteolytically activate plasminogen or to alter the interactions of plasmin with substrates and inhibitors may be the result of high affinity binding mediated by the streptokinase beta-domain. To examine this hypothesis, a chimeric streptokinase, SKbetaswap, was created by swapping the SK beta-domain with the homologous beta-domain of Streptococcus uberis Pg activator (SUPA or PauA, SK uberis), a streptokinase that cannot activate human plasminogen. SKbetaswap formed a tight complex with microplasminogen with an affinity comparable with streptokinase. The SKbetaswap-plasmin complex also activated human plasminogen with catalytic efficiencies (k(cat)/K(m) = 16.8 versus 15.2 microm(-1) min(-1)) comparable with streptokinase. However, SKbetaswap was incapable of nonproteolytic active site generation and activated plasminogen by a staphylokinase mechanism. When compared with streptokinase complexes, SKbetaswap-plasmin and SKbetaswap-microplasmin complexes had altered affinities for low molecular weight substrates. The SKbetaswap-plasmin complex also was less resistant than the streptokinase-plasmin complex to inhibition by alpha(2)-antiplasmin and was readily inhibited by soybean trypsin inhibitor. Thus, in addition to mediating high affinity binding to plasmin(ogen), the streptokinase beta-domain is required for nonproteolytic active site generation and specifically modulates the interactions of the complex with substrates and inhibitors.

Animals↗
PubMed2002

Nitration of annexin II tetramer.

Annexin II tetramer (AII(t)) is a member of the Ca(2+)- and phospholipid-binding protein family and is implicated in membrane fusion during surfactant secretion. It had previously been shown that high concentrations of nitric oxide (NO) inhibit surfactant secretion from lung type II cells. NO reacts with superoxide (O(2)(-)) to form peroxynitrite (ONOO(-)), a tyrosine nitrating agent, which is found in lungs under certain pathological conditions. It is therefore hypothesized that nitration of AII(t) by ONOO(-) may be a mechanism for the NO inhibition of regulated exocytosis. We therefore performed in vitro studies to test effects of ONOO(-) on AII(t). Western blot analysis using anti-nitrotyrosine antibodies showed a dose-dependent nitration of tyrosine residues in AII(t) treated with ONOO(-). Nitration occurred on the core domain of the p36 subunit, as well as on the p11 subunit. ONOO(-) also caused the formation of dimers between p36 and p11 subunits which were stable in the presence of heating, SDS, and beta-mercaptoethanol. AII(t)-mediated liposome aggregation was inhibited by ONOO(-) with an IC(50) of approximately 30 microM. The inhibition was abolished by urate (a scavenger of ONOO(-) and *OH), but not by mannitol (a scavenger of *OH) or superoxide dismutase (a scavenger of O(2)(-)) and appeared to be specific to AII(t), since ONOO(-) only slightly influenced annexin I-mediated liposome aggregation. The conformational change of AII(t) induced by Ca(2+) had no effect on the inhibition. Furthermore, ONOO(-) only partially inhibited the binding of AII(t) to membranes. Nitration of AII(t) also occurred in intact A549 cells, a lung epithelial cell line, treated with ONOO(-). The results of this study suggest that AII(t)-mediated liposome aggregation was inhibited by nitration of the protein.

Animals↗
PubMed2002

Checkpoint for DNA integrity at the first mitosis after oocyte activation.

Activation of oocytes, arrested at the meiosis II (MII) in mammals, initiates meiotic release, mitotic divisions, and development. Unlike most somatic cell types, MII arrested female germ cells lack an efficient DNA integrity checkpoint control. Here we present evidence showing a unique checkpoint for DNA integrity at first mitosis after oocyte activation. Mouse oocytes carrying intact DNA cleaved normally after meiotic release, whereas 50% of oocytes harboring damaged DNA manifested cytofragmentation, a morphological hallmark of apoptosis. If not activated, DNA-damaged MII oocytes did not show apoptotic fragmentation. Further, activated, enucleated oocytes or enucleated fertilized oocytes also underwent cytofragmentation, implicating cytoplasmic coordination of the fragmentation process, independent of the nucleus. Depolymerization of either actin filaments or microtubules induced no cytofragmentation, but inhibited fragmentation upon oocyte activation. During the process of fragmentation, microtubule networks formed, then microtubule asters congregated at discrete locations, around which fragmented cellular bodies formed. Mitotic spindles, however, were not formed inactivated oocytes with damaged or absent DNA; in contrast, normal mitotic spindles were formed in activated oocytes with intact DNA. These results demonstrate that damaged DNA or absence of DNA leads to cytofragmentation after oocyte activation. Further, we found a mechanism of cytoskeletal involvement in the process of cytofragmentation. In addition, possible implication of the present findings in somatic cell cloning and human clinical embryology is discussed.

Animals↗
PubMed2002

Inactivation of annexin II tetramer by S-nitrosoglutathione.

We investigated the effect of nitric oxide (NO) donors on the activities of annexin II tetramer (AIIt), a member of the Ca2+- dependent phospholipid-binding protein family. Incubation of purified AIIt with S-nitrosoglutathione (GSNO) led to the inhibition of AIIt-mediated liposome aggregation. This effect was dose-dependent with an IC50 of approximately 100 micro m. Sodium nitroprusside, another NO donor also inhibited AIIt-mediated liposome aggregation, whereas reduced glutathione, nitrate, or nitrite had no effects. GSNO also inhibited AIIt-mediated membrane fusion, but not the binding of AIIt to the membrane. GSNO only has a modest effect on liposome aggregation mediated by annexins I, III or IV. The binding of AIIt to the membrane protected the reactive sites of GSNO on AIIt. GSNO did not inhibit AIIt-mediated liposome aggregation in the presence of dithiothreitol. Taken together, our results suggest that GSNO inactivates AIIt possibly via S-nitrosylation and/or the formation of disulfide bonds.

Animals↗
PubMed2002

Mitochondrial dysfunction leads to telomere attrition and genomic instability.

Mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence, apoptosis, aging and aging-associated pathologies. Telomere shortening and genomic instability have also been associated with replicative senescence, aging and cancer. Here we show that mitochondrial dysfunction leads to telomere attrition, telomere loss, and chromosome fusion and breakage, accompanied by apoptosis. An antioxidant prevented telomere loss and genomic instability in cells with dysfunctional mitochondria, suggesting that reactive oxygen species are mediators linking mitochondrial dysfunction and genomic instability. Further, nuclear transfer protected genomes from telomere dysfunction and promoted cell survival by reconstitution with functional mitochondria. This work links mitochondrial dysfunction and genomic instability and may provide new therapeutic strategies to combat certain mitochondrial and aging-associated pathologies.

Animals↗
PubMed2002

Requirement of functional telomeres for metaphase chromosome alignments and integrity of meiotic spindles.

Telomerase deficiency in the mouse eventually leads to loss of telomeric repeats from chromosome ends and to end-to-end chromosome fusions, which result in defects in highly proliferative tissues. We show that telomere dysfunction resulting from telomerase deficiency leads to disruption of functional meiotic spindles and misalignment of chromosomes during meiotic division of oocytes in late-generation (G4) mice. However, oocytes from first-generation (G1) mice lacking telomerase showed no appreciable telomere dysfunction and exhibited chromosome alignment at the metaphase plates of meiotic spindles, in a manner similar to that of wild-type mouse oocytes. These findings suggest that telomerase does not directly influence chromosome alignment and spindle integrity. Rather, functional telomeres may be involved in mediating metaphase chromosome alignment and maintaining functional spindles during meiotic division.

Animals↗
PubMed2002

Ageing-associated aberration in meiosis of oocytes from senescence-accelerated mice.

BACKGROUND: The senescence-accelerated mouse (SAM) has been shown to exhibit ageing-associated mitochondrial dysfunction and oxidative stress, and early decline in fertility. METHODS: We compared meiotic progression of germinal vesicle oocytes between young (2-3 months) and old (10-14 months) SAM mice using triple immunostaining and fluorescence microscopy as well as Pol-Scope imaging. RESULTS: At 8-9 h of in-vitro maturation (IVM), most young SAM oocytes (86%, 32/37) were at meiosis I (MI) stage, with chromosomes aligned in the mid-region of MI spindles, whereas disrupted MI spindles and/or chromosome misalignments (45%, 18/40) and a few oocytes (20%, 8/40) with abnormal MII spindles were found in old SAM oocytes. At 15-17 h of IVM, old SAM oocytes, despite errors at MI stage, extruded a first polar body at an incidence of 88% (n = 85), which did not differ from that (92%, n = 106) of young SAM oocytes. However, oocytes from old SAM (64%, 32/50) showed aberrant MII, with chromosome misalignment and dispersal, in contrast to normal MII in most young SAM oocytes (87%, 65/75), showing chromosome alignment at the metaphase plate of MII spindles. Moreover, Pol-Scope imaging non-invasively detected disrupted or absent visible spindles and possibly aberrant chromosome alignment. CONCLUSIONS: Spindle disruption and/or chromosome misalignments at both MI and MII are associated with maternal ageing in the SAM mouse. Our findings also suggest that meiotic division lacks a competent checkpoint for spindle integrity and chromosome alignment during reproductive ageing-associated oocyte senescence.

Aging↗
PubMed2002

Haploidy but not parthenogenetic activation leads to increased incidence of apoptosis in mouse embryos.

Aneuploidy underlies failed development and possibly apoptosis of some preimplantation embryos. We employed a haploid model in the mouse to study the effects of aneuploidy on apoptosis in preimplantation embryos. Mouse metaphase II oocytes that were activated with strontium formed haploid parthenogenetic embryos with 1 pronucleus, whereas activation of oocytes with strontium plus cytochalasin D produced diploid parthenogenetic embryo controls with 2 pronuclei. Strontium induced calcium transients that mimic sperm-induced calcium oscillations, and ploidy was confirmed by chromosomal analysis. Rates of development and apoptosis were compared between haploid and diploid parthenogenetic embryos (parthenotes) and control embryos derived from in vitro fertilization (IVF). Haploid mouse parthenotes cleaved at a slower rate, and most arrested before the blastocyst stage, in contrast to diploid parthenotes or IVF embryos. Developmentally retarded haploid parthenotes exhibited apoptosis at a significantly higher frequency than did diploid parthenotes or IVF embryos. However, diploid parthenotes exhibited rates of preimplantation development and apoptosis similar to those of IVF embryos, indicating that parthenogenetic activation itself does not initiate apoptosis during preimplantation development. These results suggest that haploidy can lead to an increased incidence of apoptosis. Moreover, the initiation of apoptosis during preimplantation development does not require the paternal genome.

Animals↗
PubMed2002

Apoptosis recruits two-pore domain potassium channels used for homeostatic volume regulation.

Cell shrinkage is an incipient hallmark of apoptosis and is accompanied by potassium release that decreases the concentration of intracellular potassium and regulates apoptotic progression. The plasma membrane K+ channel recruited during apoptosis has not been characterized despite its importance as a potential therapeutic target. Here we provide evidence that two-pore domain K+ (K(2P)) channels underlie K+ efflux during apoptotic volume decreases (AVD) in mouse embryos. These K(2P) channels are inhibited by quinine but are not blocked by an array of pharmacological agents that antagonize other K+ channels. The K(2P) channels are uniquely suited to participate in the early phases of apoptosis because they are not modulated by common intracellular messengers such as calcium, ATP, and arachidonic acid, transmembrane voltage, or the cytoskeleton. A K+ channel with similar biophysical properties coordinates regulatory volume decreases (RVD) triggered by changing osmotic conditions. We propose that K(2P) channels are the pathway by which K+ effluxes during AVD and RVD and that apoptosis co-opts mechanisms more routinely employed for homeostatic cell volume regulation.

Animals↗
PubMed2002

[Immunodeficiency tuberculosis: report on 5 autopsy cases].

OBJECTIVE: To improve the awareness of immunodeficiency tuberculosis. METHODS: 5 autopsy cases of immunodeficiency tuberculosis from 1972 to 2000 in two hospitals were reviewed. RESULTS: The 5 cases were found to have hypoplasia of or damage in the thymus, among them 3 had massive tuberculous lymphadenitis lesions. Multiorgan lesions were found more in both lungs than in other organs, accompanied by lymphatic spread and blood dissemination. The microscopic feature was atypical tuberculosis with great amounts of Mycobacterium tuberculosis. CONCLUSIONS: Hypoplasia of or damage in the thymus and peripheral lymphoid tissue caused deficiency in the immune response, which resulted in the death of the patients with generalised tuberculosis by blood dissemination and lymphatic spread. The underlying mechanism of immunodeficiency tuberculosis is largely unknown, and further research is needed.

Adolescent↗
PubMed2002

Sentinel lymph nodes lymphoscintigraphy and biopsy in breast cancer.

OBJECTIVES: To determine the clinical value of sentinel lymph node (SLN) detection by lympho- scintigraphy and gamma ray detecting probe (GDP) and to assess the value of hematoxylin and eosin (H&E) staining combined with immunohistochemistry (IHC) analys is for detecting micrometastasis in lymph nodes (LNs). METHODS: Forty-two patients with breast cancer were included in this study. (99)Tc(m)-dextran was injected peritumourally. Lymphoscintigraphy images were obtained in anterior and lateral views. SLNs were removed with the aid of GDP during surgery. A standard axillary lymph nodes (ALNs) dissection was performed. All lymph nodes were first analyzed by HE staining. When all of the SLNs in a patient were negative, the ALNs were subjected to additional HE staining combined with IHC analysis. RESULTS: SLNs were successfully detected and removed in 39 (92.9%) of the 42 patients. The sensitivity, specificity and accuracy of SLN biopsy were 92.9% (13 in 14), 100% (25 in 25) and 97.4% (38 in 39) respectively. Additional HE staining combined with IHC analysis of the ALNs detected micrometastasis in 3 SLNs (2 cases), but there were no positives in the non-sentinal lymph nodes (NSLNs). CONCLUSIONS: This study suggests that lymphoscintigraphy and GDP may be used to detect SLN. Additional HE staining combined with IHC analysis of the ALNs may help predict micrometastasis. Biopsy of SLN may be an accurate method for staging breast cancer.

Adult↗