Biomedical subjects

X Lin

Publications and source records attributed to X Lin.

At least 217 records · Page 12Linked to original sources

PubMed1999

Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development.

The Drosophila sugarless and sulfateless genes encode enzymes required for the biosynthesis of heparan sulfate glycosaminoglycans. Biochemical studies have shown that heparan sulfate glycosaminoglycans are involved in signaling by fibroblast growth factor receptors, but evidence for such a requirement in an intact organism has not been available. We now demonstrate that sugarless and sulfateless mutant embryos have phenotypes similar to those lacking the functions of two Drosophila fibroblast growth factor receptors, Heartless and Breathless. Moreover, both Heartless- and Breathless-dependent MAPK activation is significantly reduced in embryos which fail to synthesize heparan sulfate glycosaminoglycans. Consistent with an involvement of Sulfateless and Sugarless in fibroblast growth factor receptor signaling, a constitutively activated form of Heartless partially rescues sugarless and sulfateless mutants, and dosage-sensitive interactions occur between heartless and the heparan sulfate glycosaminoglycan biosynthetic enzyme genes. We also find that overexpression of Branchless, the Breathless ligand, can partially overcome the requirement of Sugarless and Sulfateless for Breathless activity. These results provide the first genetic evidence that heparan sulfate glycosaminoglycans are essential for fibroblast growth factor receptor signaling in a well defined developmental context, and support a model in which heparan sulfate glycosaminoglycans facilitate fibroblast growth factor ligand and/or ligand-receptor oligomerization.

Amidohydrolases↗

PubMed1999

Analysis of repeated hemoglobin measures in full-term, normal birth weight Kenyan children between birth and four years of age. III. The Asemobo Bay Cohort Project.

Anemia is an important public health problem. During very early childhood numerous factors affect hemoglobin (Hb) concentration over time, making single cross-sectional measurements difficult to interpret when studying the natural history of anemia or evaluating anemia control strategies. We analyzed repeated Hb measures contributed by 942 Kenyan children between birth and 48 months of life using a mixed effects model, with a regression spline used to describe the population mean Hb profile, and random intercepts and slopes and first-order autoregressive correlation structure to accommodate the within-individual correlation among the repeated Hb measures. The approach facilitates the study of time-stationary and time-varying covariates that influence Hb in early life. The fitted mean Hb profile obtained from the analytic model is consistent with the observed mean Hb of the study population. Village of residence was associated with greatest difference in mean Hb at time of birth (16 versus 19 g/dL; P < 0.0001). Monthly weight-for-age was also associated with mean Hb after 3 months of age. This is the first description of an analysis strategy specifically for repeated Hb measures collected in a longitudinal field study in Africa. The strategy will facilitate improved study of time-varying covariates thought to influence pediatric anemia.

Adolescent↗

PubMed1999

[Cost-effectiveness analysis of treatment of chronic hepatitis B with interferon in Chinese city].

OBJECTIVE: In this article, we evaluated the economic significance of treating HBeAg-positive chronic hepatitis B with interferon in Chinese population. METHODS: Cohort of 1,000 hypothetical HBeAg-positive chronic hepatitis B patients treated with interferon was compared to patients with routine treatment in respect of cost and effectiveness. The costs of routine treatment were estimated by surveys in four Chinese cities (Beijing, Shanghai, Nanning and Shijiazhuang). Natural history of HBeAg-positive chronic hepatitis B and the efficacy of interferon were determined by meta-analysis. Outcome of the disease and medical cost of the two cohorts were predicted over a period of 30 years using survival analysis. Thus, cost per life year and cost per QALY(Quality adjusted life year) with the interferon treatment were calculated. Sensitivity analysis was performed to test the firmness of the conclusion. RESULTS: Costs per life year and per QALY saved were no more than 2,359 Yuan(RMB) and 1,775 Yuan (RMB) respectively. In Shanghai and Beijing, medical costs could be saved due to the use of interferon. CONCLUSIONS: Treatment of chronic hepatitis B with interferon was cost-effective and should be considered in the allocation of health resource in Chinese cities.

Antiviral Agents↗

PubMed1999

[Long-term efficacy study of hepatitis B vaccination in newborns--results of 11 years' follow-up].

OBJECTIVE: To evaluate the long-term efficacy of hepatitis B(HB) vaccination in newborns and the need for a booster dose. This research is one of the longest HB vaccine follow-up studies in the world with its subjects came from a program of universal infant HB vaccination. METHODS: Children who were born in 1986 and immunized with hepatitis B vaccine at birth were followed up at least once a year. Serum HBsAg, anti-HBc and anti-HBs were tested. At the 5th year after the first dose the prevalence of hepatitis B infection in the children in other district who were also born in 1986 and remained unvaccinated was surveyed as external controls. Random sampling was applied and the possible bias was analyzed. The trends of the positive rates of serum HBsAg, anti-HBs and anti-HBc in the immunized cohort were studied. With external control, the long-term efficacy of HB vaccination was calculated. RESULTS: The positive rates of HBsAg in the vaccine group from the first to eleventh year were 0.46%-0.98% and were below than those of baseline and external control. HBsAg rates in the cohort at different ages were similar with an average of 0.70%(25/3 578). The long-term efficacy of newborn vaccination was 85.42% (95% confidant interval: 70.11%-100%). CONCLUSIONS: The efficacy of HB vaccine was long-lasting and a booster dose was not necessary at least up to age 11 years.

Female↗

PubMed1999

Experimental studies on topoisomerase inhibitor camptothecin as an antipsoriatic agent.

OBJECTIVES: To elucidate the therapeutic mechanism of topical camptothecin (CPT) in treating psoriasis and to detect the effects of CPT on keratinocyte proliferation, differentiation and apoptosis. METHODS: Mitotic numbers in mouse vaginal epithelium at estrus and numbers of scale with granular layer per 100 scales in mouse tail epidermis were determined in vivo. Experiments on cultured normal human keratinocytes were performed using the methods of crystal violet staining, absorbance-cell number converting, cell counting and quantitation of morphologic changes during differentiation, transglutaminase assay and nucleosomal enrichment assay. RESULTS: Inhibition of cell proliferation and promotion of cell differentiation by camptothecin were showed in animal models and were reconfirmed in cultured keratinocytes. Apoptosis was induced by camptothecin and was showed by activation of "tissue" transglutaminase and increase in nucleosomes. The endonuclease activity was reduced by an endonuclease inhibitor aurintricarboxylic acid. CONCLUSION: The therapeutic effects of camptothecin on psoriasis can at least partly be explained by its multiple effects on DNA as a topoisomerase inhibitor.

Animals↗

PubMed1999

[Effect of Yiqi Zishen granule on ultrastructure of glomeruli of IgA nephropathy in mice].

OBJECTIVE: To study the effect and therapeutical mechanism of Yiqi Zishen granule (YQZSG) in treating IgA nephropathy. METHODS: One hundred and fifty mice were divided into 5 groups randomly, in every treatment group, the relevant drugs were given. Their kidney tissues were observed with light microscope and electron microscope in batches at the 3rd, 6th, 9th and 12th week. RESULTS: The glomerular mesangial cells and mesangial matrix were proliferative in the model group at the 6th, 9th and 12th week. The light density of glomeruli, the mesangial area, the numeral density of mesangial cells and the light density of mesangial matrix in the model group were obviously higher, the change of large and small dosage YQZSG group and positive Chinese drug group were similar, but milder in pathological degree. The light density of glomerulus area, the mesangial area, the numeral density of mesangial cells and the light density of mesangial matrix in large dosage YQZSG group were significantly lower than those in the model group (P < 0.05 or P < 0.01). CONCLUSION: YQZSG could inhibit the proliferation of mesangial cells and the mesangial matrix in IgA nephropathy.

Animals↗

PubMed1999

[Applying combination of ultrasound and CT to diagnose paralaryngeal space tumor].

OBJECTIVE: To explore an effective way to diagnose parapharyngeal space tumor. METHODS: The clinical data of 25 cases of this type of tumor, diagnosed by combinating ultrasound examination and CT scan, were analysed. RESULTS: The diagnosis correspondence rate by the combinating way of ultrasound and CT is 92%. The combination of the two methods is likely able to reveal the overall shape, extend and feature of tumor, and to assist us in decision of the entrance of operation. CONCLUSION: The combination of ultrasound diagaosis and CT scan is of satisfactory clinical value in diagnosis of parapharyngeal space tumor.

Adolescent↗

PubMed1999

[Detection of circulating antigen in serum and cerebrospinal fluid for diagnosis of cerebral cysticercosis].

AIM: To detect circulating antigen(CAg) in serum and cerebrospinal fluid(CSF) from patients with cerebral cysticercosis with specific antiserum by sandwich ELISA. METHODS: Antisera were prepared from rabbits immunized respectively with 3 antigens with molecule weights of 64 kDa, 53 kDa, 32 kDa-30 kDa extracted from Cysticercus cellulosae and purified by SDS-PAGE. RESULTS: When samples from patients were tested with antiserum against 53 kDa antigen, the CAg positive rate was 93.8% in serum and 91.7% in CSF of 32 patients with active cysticercosis, whereas only one positive was found in CSF in 16 patients with inactive cysticercosis. The detection rate of CAg was significantly higher with anti-53 kDa antiserum than with anti-64 kDa and anti-32 kDa-30 kDa antiserum. CONCLUSION: Sandwich-ELISA using antiserum against 53 kDa antigen to detect CAg was found to be a promising assay for diagnosis and evaluation of treatment efficacy of active cerebral cysticercosis in terms of its high sensitivity and specificity.

Animals↗

PubMed1999

[The prognostic value of virology and immunology markers in Chinese HIV-1 infected people].

OBJECTIVE: To study the prognostic value of virology and immunology markers in Chinese HIV-1 infected people and their correlation. METHODS: We studied 190 HIV infected people/AIDS patients' samples from China. Plasma viral load, P24 antigen, virus culture, CD4 positive T lymphocyte (CD4) count and CD8 positive T lymphocyte(CD8) count were tested. Test groups were divided according to clinical staging diagnosis from physicians. The data were analyzed in aspects of their relations with clinical status and correlations among all the above markers. RESULTS: Plasma viral load, CD4 count and CD4/CD8 ratio showed significant difference between asymptomatic stage and symptomatic stages (P < 0.01), also between asymptomatic and AIDS stages(P < 0.001). Virus culture positive rate increased significantly from asymptomatic to symptomatic stage. No significant clinical change was observed associating with P24 antigen positive rate. CD8 count decreased slightly when AIDS occurred (P < 0.001). Close correlation was observed between plasma viral load, CD4 count and CD4/CD8 ratio. CONCLUSION: Viral load, CD4 count and CD4/CD8 ratio are useful indicators to AIDS prognosis and virus culture can be a supplementary marker. p24 antigen detection seems no diagnostic value to disease progress. The significance of CD8 change will be further studied.

Biomarkers↗

PubMed1998

Biodegradable positively charged ion exchange beads: a novel biomaterial for enhancing soft tissue repair.

Previous work in the area of vulnerary agents is extensive. One material of focus has been positively charged ion exchange beads, which have been shown to promote a variety of wound-healing responses in several models. The goal of this work was to improve upon the clinical utility of positively charged dextran beads by creating a biodegradable version that maintains the material's inherent efficacy. A chemical method consisting of a sodium periodate oxidation was used to create a degradable diethylaminoethanol crosslinked dextran bead. The ability of this process to create a degradable bead was verified in vitro and in vivo. Furthermore, efficacy was shown in a rat linear incision model for a variety of beads exhibiting different degradation rates. The results show that efficacy is maintained by a degradable bead, but there is a diminution of the magnitude of the response as the mass loss rate is increased. Efficacy also was investigated for a moderate but completely degrading bead material over time and dose. Wound breaking strength was evaluated at days 7, 10, 14, 21, and 28 for degradable beads at doses of 10 mg/mL and 50 mg/mL. Although little difference in efficacy was noted for the increased dose, statistically significant increases over control were seen at days 7, 10, and 14 for the 10 mg/mL dose and at days 10 and 14 for the 50 mg/mL dose. At days 21 and 28 there were no differences between treated and control wounds.

Animals↗

PubMed1998

Visualization of unoccupied and occupied gonadotropin-releasing hormone receptors in living cells.

Three chimeras of the rat GnRH receptor (rGnRHR) and an enhanced green fluorescent protein (GFP) were assessed to examine their suitability as probes of the receptor in transfected GH3 cells. Direct fusion of GFP to the N or C terminus of the rGnRHR abolished the receptor ligand binding affinity and the chimeric receptors were intracellularly localized. In contrast, rGnRHR-Ctail-GFP, a fusion of the N-terminus of the GFP to the C-terminus of the rGnRHR with the intracellular C-terminal tail of the catfish GnRHR as an intermediate spacer, was functional in terms of plasma membrane localization, ligand binding ability, receptor-mediated signal transduction and pattern of homologous down-regulation. The functional chimera of GnRHR and GFP provided a useful model for observation of GnRHR distribution and agonist-stimulated trafficking in living cells.

Animals↗

PubMed1998

Perforin-dependent neurologic injury in a viral model of multiple sclerosis.

In this study we demonstrate perforin-mediated cytotoxic effector function is necessary for viral clearance and may directly contribute to the development of neurologic deficits after demyelination in the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. We previously demonstrated major histocompatability complex (MHC) class I-deficient (beta2m-deficient) mice with an otherwise resistant genotype develop severe demyelination with minimal neurologic disease when chronically infected with TMEV. These studies implicate CD8(+) T cells as the pathogenic cell in the induction of neurologic disease after demyelination. To determine which effector mechanisms of CD8(+) T cells, granule exocytosis or Fas ligand expression, play a role in the development of demyelination and clinical disease, we infected perforin-deficient, lpr (Fas mutation), and gld (Fas ligand mutation) mice with TMEV. Perforin-deficient mice showed viral persistence in the CNS, chronic brain pathology, and demyelination in the spinal cord white matter. Perforin-deficient mice demonstrated severely impaired MHC class I-restricted cytotoxicity against viral epitopes, but normal MHC class II-restricted delayed-type hypersensitivity responses to virus antigen. Despite demyelination, virus-infected perforin-deficient mice showed only minimal neurologic deficits as indicated by clinical disease score, activity monitoring, and footprint analysis. Perforin- and MHC class II-deficient mice (with functional CD8(+) T cells and perforin molecules and an H-2(b) haplotype) had comparable demyelination and genotype, however, only the latter showed severe clinical disease. Gld and lpr mice demonstrated normal TMEV-specific cytotoxicity and maintained resistance to TMEV-induced demyelinating disease. These studies implicate perforin release by CD8(+) T cells as a potential mechanism by which neurologic deficits are induced after demyelination.

Animals↗

PubMed1998

Crystal structure of the catalytic domain of human plasmin complexed with streptokinase.

Streptokinase is a plasminogen activator widely used in treating blood-clotting disorders. Complexes of streptokinase with human plasminogen can hydrolytically activate other plasminogen molecules to plasmin, which then dissolves blood clots. A similar binding activation mechanism also occurs in some key steps of blood coagulation. The crystal structure of streptokinase complexed with the catalytic unit of human plasmin was solved at 2.9 angstroms. The amino-terminal domain of streptokinase in the complex is hypothesized to enhance the substrate recognition. The carboxyl-terminal domain of streptokinase, which binds near the activation loop of plasminogen, is likely responsible for the contact activation of plasminogen in the complex.

Binding Sites↗

PubMed1998

Expression and functional analysis of mouse EXT1, a homolog of the human multiple exostoses type 1 gene.

Hereditary multiple exostoses (EXT) is a genetically heterogeneous, autosomal dominant skeletal disorder. The gene for EXT1 maps to human chromosome 8q24.1 and encodes an evolutionary conserved protein that is a member of a multigene family. The mouse homolog of human EXT1 protein is 99% similar to its human counterpart. Here, we present the expression profiles of the mouse EXT1 gene. EXT1 mRNA is initially expressed at 6.5 days post-coitum (d.p.c.), which coincides with gastrulation of the mouse embryo. Whole mount in situ hybridization with 10.5 to 12.5 d.p.c. mouse embryos showed a high level of expression of EXT1 mRNA in developing limb buds. Epitope tagging experiments revealed the endoplasmic reticulum localization of EXT1 protein. This localization was consistent with a hydrophobic stretch of amino acids present at the N-terminal end of the EXT1 protein. These results provide novel information on the function of EXT1 and the etiology of hereditary multiple exostoses.

3T3 Cells↗

PubMed1998

Characterization of the structural and functional changes of hemoglobin in dimethyl sulfoxide by spectroscopic techniques.

Circular dichroism (CD), fourier transform infrared (FTIR), and fluorescence spectroscopy were used to explore the effect of dimethyl sulfoxide (DMSO) on the structure and function of hemoglobin (Hb). The native tertiary structure was disrupted completely when the concentration of DMSO reached 50% (v/v), which was determined by loss of the characteristic Soret CD spectrum. Loss of the native tertiary structure could be mainly caused by breaking the hydrogen bonds, between the heme propionate groups and nearby surface amino acid residues, and by disorganizing the hydrophobic interior of this protein. Upon exposure of Hb to 52% DMSO for ca. 12 h in a D2O medium no significant change in 1652 cm-1 band of the FTIR spectrum was produced, which demonstrated that alpha-helical structure predominated. When the concentration of DMSO increased to 57%: (1) the band at 1652 cm-1 disappeared with the appearance of two new bands located at 1661 and 1648 cm-1; (2) another new band at 1623 cm-1 was attributed to the formation of intermolecular beta-sheet or aggregation, which was the direct consequence of breaking of the polypeptide chain by the competition of S&z.dbnd6;O groups in DMSO with C&z.dbnd6;O groups in amide bonds. Further increasing the DMSO concentration to 80%, the intensity at 1623 cm-1 increased, and the bands at 1684, 1661 and 1648 cm-1 shifted to 1688, 1664 and 1644 cm-1, respectively. These changes showed that the native secondary structure of Hb was lost and led to further aggregation and increase of the content of 'free' amide C&z.dbnd6;O groups. In pure DMSO solvent, the major band at 1664 cm-1 indicated that almost all of both the intermolecular beta-sheet and any residual secondary structure were completely disrupted. The red shift of the fluorescence emission maxima showed that the tryptophan residues were exposed to a greater hydrophilic environment as the DMSO content increased. CO-binding experiment suggested that the biological function of Hb was disrupted seriously even if the content of DMSO was 20%.

Animals↗

PubMed1998

Caenorhabditis elegans contains two distinct acid sphingomyelinases.

Mounting evidence supports a role for acid sphingomyelinase (ASM) in cellular stress signaling. Only murine and human sphingomyelinases have been defined at the molecular level. These enzymes are the products of a conserved gene and at the amino acid level share 82% identity. In this study, we show that the nematode Caenorhabditis elegans possesses two ASMs, termed ASM-1 and ASM-2 encoded by two distinct genes, but lacks detectable neutral sphingomyelinase activity. The C. elegans ASMs are about 30% identical with each other and with the human and murine enzymes. The conserved regions include a saposin-like domain, proline-rich domain, and a putative signal peptide. In addition, 16 cysteines distributed throughout the molecules, and selected glycosylation sites, are conserved. The expression of these genes in C. elegans is regulated during development. Asm-1 is preferentially expressed in the embryo, whereas asm-2 is predominantly expressed in postembryonic stages. When transfected as Flag-tagged proteins into COS-7 cells, ASM-1 is found almost entirely in a secreted form whereas only 20% of ASM-2 is secreted. Only the secreted forms display enzymatic activity. Furthermore, ASM-2 requires addition of Zn2+ to be fully active, whereas ASM-1 is active in the absence of cation. C. elegans is the first organism to display two ASMs. This finding suggests the existence of an ASM gene family.

Amino Acid Sequence↗

PubMed1998

Theiler's virus infection of genetically susceptible mice induces central nervous system-infiltrating CTLs with no apparent viral or major myelin antigenic specificity.

Intracranial infection of susceptible mice with Theiler's virus results in persistent infection and spinal cord demyelination similar to human multiple sclerosis. While central nervous system infiltrating lymphocytes (CNS-ILs) in these mice display no virus-specific CTL activity, the cells were found to be activated killers using a specificity-independent assay. We previously demonstrated that the depletion of T cells in persistently infected mice significantly decreases demyelinating disease. Consequently, we have investigated the killing pathways employed by CNS-ILs that are isolated from persistently infected animals, the relative contribution of CD4 and CD8 cells in the generation of these CTLs, and the reactivity of this cell population to two putative autoantigens in the CNS. In vitro or in vivo manipulation of T cell populations using Abs or genetic knockout strategies demonstrate that the cytotoxic activity is primarily mediated by CD8+ T cells, and that perforin is an important molecule in the effector pathway. Since effector functions in infected mice were not inhibited by the depletion of CD4 cells with mAb but was blocked genetically in CD4 knockout mice, CD4+ T cells appear to play a helper role in the generation of CD8+ CTLs. We found no evidence of autoimmune-mediated demyelination, as the CD8+ CTLs were not reactive to two major myelin autoantigens, myelin basic protein and proteolipid protein. Our finding that CNS-ILs that are isolated from mice susceptible to persistent virus infection are neither specific for virus or myelin autoantigens is consistent with the possibility that CD8+ CTLs mediate CNS damage as a result of nonspecific activation by virus.

Animals↗

PubMed1998

BDNF accelerates gene expression in cultured cerebellar granule neurons.

This study reports that in purified cultures of postnatal cerebellar granule cells, BDNF significantly accelerated GABAA receptor alpha 6 subunit (GABAA alpha 6) mRNA expression, a marker for terminally differentiated cerebellar granule neurons, and also accelerated p21cip1 expression. p21cip1 is a general cyclin-dependent kinase (Cdk) inhibitor that can inhibit progression through the cell cycle. Alternatively, the expression of p27kip1, another Cdk inhibitor closely related to p21cip1, is not modified by BDNF. In cultured granule cells, the increase in p21cip1 expression induced by BDNF occurred after dividing granule cells had left the cell cycle and thus was not required to direct granule neuron precursors out of the cell cycle. p21cip1 may have an alterative function during granule neuron terminal differentiation, separate from its ability to regulate cell cycle exit. This report shows that, in vitro, BDNF accelerates granule cell gene expression and may thus modulate cerebellar granule cell differentiation.

Animals↗