Biomedical subjects

X Lin

Publications and source records attributed to X Lin.

At least 109 records · Page 6Linked to original sources

PubMed2001

[Effects of cactus, alove veral, momorcica charantia on reducing the blood glucose of diabetic mice].

The effects of cactus, alove veral and momorcica charantia on reducing the blood glucose level of mice were observed. The diabetic model with no symptom in mice was established by injection of streptozotocin(STZ) 80 mg/kg BW into abdominal cavity for 11 days. The diabetic mice were randomly divided into 8 groups: STZ diabetic model, diet A, diet B, cactus, alove veral, momordica charantia and glyburide groups. Cactus (60 g/kg BW), alove veral (60 g/kg BW), and momordica charantia (30 g/kg BW) were administrated orally each day to the diabetic mice for another 21 days. Serum glucose of mice fasting for 12 hours and 2 hours after meal was determined with the method of glucose-oxidase at the 21th day of the experiment. The results showed that serum glucose levels of diabetic mice were significantly higher than the normal control group (P < 0.01). After giving diet A, cactus, alove veral and momorcica charantia juice for 21 days, the serum glucose concentration of these diabetic mice were significantly lower than STZ diabetic model group (P < 0.01) but still higher than the normal control group.

Aloe↗

PubMed2001

[Clinical analysis of 184 eyes with perforating injury].

OBJECTIVE: Try to understand the occurrence and the prognosis of eyes with perforating injury. METHODS: By using retrospective analysis on 184 eyes with perforating injury. RESULTS: Perforating eyes hold 9.5% of total impatient, mostly happened in working place, foreign body is the main cause, the age is mostly from ten to 60, centralize from 20 to 30. the complication includes leucoma, cataract, vitreous hemorrhage etc. After operation, 71 eyes had visual acuity < 0.05. 60.85% of the patients had visual acuity > or = 0.05 and 0.65% of the patients are not cooperative. CONCLUSION: The rate of blindness on eyes with perforating injury is high, it implies that perforating injury could be prevented and treated from the data we collected.

Adolescent↗

PubMed2001

[Pathological changes of diffuse Pneumocystis carinii infection in the liver of an AIDS patient].

OBJECTIVE: To examine the pathological changes in the liver of an AIDS patient with complicated infection of Pneumocystis carinii(PC). METHODS: A liver biopsy was made. The tissue was stained with HE, PAS, Giemsa, GMS, and acid-fast staining, and examined under light microscope and transmission electron microscope. RESULTS: Granulomas (acid-fast negative) in the tissue and numerous pathogens (PAS positive) in hepatic sinusoids were detected. Giemsa and GMS staining and electron microscopy all confirmed that the pathogen was Pneumocystis carinii. CONCLUSION: The pathological findings revealed a diffuse extrapulmonary infection of Pneumocystis carinii in the patient of AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2001

[Studies on ultrastructure and histochemistry of Trichomonas vaginalis adhering to vaginal mucosa of rats].

OBJECTIVE: To study interaction between Trichomonas vaginalis and epithelium of genital tract of host as well as the pathogenesis of T. vaginalis. METHODS: Immunohistochemical technique was used to observe the adhering process of T. vaginalis to vaginal mucosa in rats by transmission and scanning microscopy. RESULTS: T. vaginalis were shown to be PAS positive and clusters of T. vaginalis were found to adhere to columnar epithelium rich in mucopolysaccharide on the surface of vaginal mucosa as viewed in sections of the middle and upper parts of the orgen. T. vaginalis was positive for cathepsin. And the membrane of epithelial cells was often damaged by the released hydrolase. The parasite was also positive for actin; the microfilament bundles were arranged in reticular form in ameboid T. vaginalis. The latter would penetrate between epithelial cells, and its filiform pseudopodia would invade the interspace of microvilli of the epithelium, to encircle and gradually phagocytize microvilli. Digitiform pseudopodia would insert between epithelial cells and encircle part of them. A few T. vaginalis were found to adhere to the keratinized epithelium between mucosal folds as shown in the sections of the lower part of vagina. CONCLUSION: T. vaginalis is inclined to parasitise vaginal fornix because the superficial epithelial cells there are rich in mucinogen granules and abundant microvilli exist. After adhering, T. vaginalis releases hydrolase to digest and phagocytize epithelium which may directly damage the epithelium of the genital canal. Moreover, T. vaginalis would take in mucopolysaccharide to affect the normal clearance process of vagina, resulting in inflammation of parasitized tissue. The cytoskeleton, cell coat, polymorphism of pseudopodia and lysosome of T. vaginalis play an important role in the courses of movement, adhesion, encirclement, phagocytosis and digestion.

Actins↗

PubMed2000

Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

Arabidopsis↗

PubMed2000

Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling.

Smads are important intracellular signaling effectors for transforming growth factor-beta (TGF-beta) and related factors. Proper TGF-beta signaling requires precise control of Smad functions. In this study, we have identified a novel HECT class ubiquitin E3 ligase, designated Smurf2, that negatively regulates Smad2 signaling. In both yeast two-hybrid and in vitro binding assays, we found that Smurf2 could interact with receptor-activated Smads (R-Smads), including Smad1, Smad2, and Smad3 but not Smad4. Ectopic expression of Smurf2 was sufficient to reduce the steady-state levels of Smad1 and Smad2 but not Smad3 or Smad4. Significantly, Smurf2 displayed preference to Smad2 as its target for degradation. Furthermore, Smurf2 exhibited higher binding affinity to activated Smad2 upon TGF-beta stimulation. The ability of Smurf2 to promote Smad2 destruction required the HECT catalytic activity of Smurf2 and depended on the proteasome-dependent pathway. Consistent with these results, Smurf2 potently reduced the transcriptional activity of Smad2. These data suggest that a ubiquitin/proteasome-dependent mechanism is important for proper regulation of TGF-beta signaling.

Cell Line↗

PubMed2000

The NF-kappa B-inducing kinase induces PC12 cell differentiation and prevents apoptosis.

NF-kappa B has been implicated in the survival and differentiation of PC12 cells. In this study, we examined the effect of the NF-kappa B-inducing kinase (NIK) on these processes. When inducibly expressed in PC12 cells, a kinase-proficient but not -deficient form of NIK promoted neurite process formation and mediated anti-apoptotic signaling. As expected, NIK expression led to I kappa B kinase activation and induced nuclear translocation of NF-kappa B. However, NIK-induced neurite outgrowth was only partially blocked by concomitant expression of a nondegradable form of I kappa B alpha that completely blocks NF-kappa B induction. In search of additional signaling pathways activated by NIK, we now demonstrate that NIK activates MEK1 phosphorylation and induces the Erk1/Erk2 MAPK pathway. Treatment of PC12 cells with PD98059, a MEK1 inhibitor, potently blocked neurite process formation; however, a dominantly interfering mutant of the upstream Shc adapter failed to alter this response. These findings reveal a new function for NIK as a MEK1-dependent activator of the MAPK pathway and implicate both the I kappa B kinase and MAPK signaling cascades in NIK-induced differentiation of PC12 cells.

Animals↗

PubMed2000

Mild and efficient functionalization at C6 of purine 2'-deoxynucleosides and ribonucleosides.

[reaction: see text] Treatment of sugar-protected inosine and 2'-deoxyinosine derivatives with a cyclic secondary amine or imidazole and I(2)/Ph(3)P/EtN(i-Pr)(2)/(CH(2)Cl(2) or toluene) gave quantitative conversions into 6-N-(substituted)purine nucleosides. S(N)Ar reactions with 6-(imidazol-1-yl) derivatives gave 6-(N, O, or S)-substituted products. The 6-(benzylsulfonyl) group underwent S(N)Ar displacement with an arylamine at ambient temperature.

Deoxyribonucleosides↗

PubMed2000

In vitro selection of an RNA sequence that interacts with high affinity with thymidylate synthase.

Previous studies have shown that the repressive effect of thymidylate synthase (TS) mRNA translation is mediated by direct binding of TS itself to two cis-acting elements on its cognate mRNA. To identify the optimal RNA nucleotides that interact with TS, we in vitro synthesized a completely degenerate, linear RNA pool of 25 nt and employed in vitro selection to isolate high affinity RNA ligands that bind human TS protein. After 10 rounds of selection and amplification, a single RNA molecule was selected that bound TS protein with nearly 20-fold greater affinity than native, wild-type TS RNA sequences. Secondary structure analysis of this RNA sequence predicted it to possess a stem-loop structure. Deletion and/or modification of the UGU loop element within the RNA sequence decreased binding to TS by up to 1000-fold. In vivo transfection experiments revealed that the presence of the selected RNA sequence resulted in a significant increase in the expression of a heterologous luciferase reporter construct in human colon cancer H630 and TS-overexpressing HCT-C:His-TS+ cells, but not in HCT-C18 cells expressing a functionally inactive TS. In addition, the presence of this element in H630 cells leads to induced expression of TS protein. An immunoprecipitation method using RT-PCR confirmed a direct interaction between human TS protein and the selected RNA sequence in transfected human cancer H630 cells. This study identified a novel RNA sequence from a degenerate RNA library that specifically interacts with TS.

Base Sequence↗

PubMed2000

NF-kappa B signaling promotes both cell survival and neurite process formation in nerve growth factor-stimulated PC12 cells.

Nerve growth factor binds to the TrkA and p75(NTR) (p75) and generates signals leading to neuronal cell survival, differentiation, and programmed cell death. Here we describe a series of experiments involving selective activation of either TrkA or p75 in which distinct cell-signaling intermediates promote different cellular consequences. We analyzed pheochromocytoma 12 (PC12) cells stably expressing chimeras consisting of the extracellular domain of PDGF receptor (PDGFR) fused to the transmembrane and cytoplasmic segments of p75 or TrkA. Because PC12 cells lack endogenous PDGFR, addition of PDGF to these cell lines permits selective activation of the p75 or TrkA responses without stimulating endogenous receptors. Although both p75 and TrkA activated nuclear factor-kappaB (NF-kappaB), we show that distinct proximal-signaling intermediates are used by each receptor. A dominant-negative mutant of TRAF6 blocked p75- but not TrkA-mediated induction of NF-kappaB. Conversely a dominant-negative mutant of Shc inhibited TrkA but not p75 activation of NF-kappaB. Both of these distinct signaling pathways subsequently converge, leading to activation of the IkappaB kinase complex. Moreover, the activation of NF-kappaB by these distinct pathways after stimulation of either TrkA or p75 leads to different physiological consequences. Blocking p75-mediated activation of NF-kappaB by ecdysone-inducible expression of a nondegradable mutant of IkappaBalpha significantly enhanced apoptosis. In contrast, blocking NF-kappaB induction via TrkA significantly inhibited neurite process formation in PC12 cells. Together these findings indicate that, although both of these receptors lead to the activation of NF-kappaB, they proceed via distinct proximal-signaling intermediates and contribute to different cellular outcomes.

Animals↗

PubMed2000

Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor.

Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease involved in the production of beta-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution. The active site of memapsin 2 is more open and less hydrophobic than that of other human aspartic proteases. The subsite locations from S4 to S2' are well defined. A kink of the inhibitor chain at P2' and the change of chain direction of P3' and P4' may be mimicked to provide inhibitor selectivity.

Amyloid Precursor Protein Secretases↗

PubMed2000

Smad2, Smad3 and Smad4 cooperate with Sp1 to induce p15(Ink4B) transcription in response to TGF-beta.

Transforming growth factor-beta (TGF-beta) arrests growth of epithelial cells by inducing the transcription of p15(Ink4B), a cyclin-dependent kinase inhibitor. In this study, we demonstrate that p15(Ink4B) induction was mediated by a TGF-beta-induced complex of Smad2, Smad3, Smad4 and Sp1. Mutations in the Sp1- or Smad-binding sequences decreased or abolished the TGF-beta responsiveness of the p15(Ink4B) promoter. Interference with, or deficiency in, Smad2, Smad3 or Smad4 functions also reduced or abolished the TGF-beta-dependent p15(Ink4B) induction, whereas the absence of Sp1 reduced the basal and TGF-beta-induced p15(Ink4B) transcription. In the nucleoprotein complex, Smad2 interacted through its C-domain with Sp1 and enhanced the DNA binding and transcriptional activity of Sp1. Smad3 interacted indirectly with Sp1 through its association with Smad2 and/or Smad4, and bound directly to the p15(Ink4B) promoter. Finally, Smad4 interacted through its N-domain with Sp1. Our data demonstrate the physical interactions and functional cooperativity of Sp1 with a complex of Smad2, Smad3 and Smad4 in the induction of the p15(Ink4B) gene. These findings explain the tumor suppressor roles of Smad2 and Smad4 in growth arrest signaling by TGF-beta.

Activin Receptors, Type I↗

PubMed2000

The CD4-mediated immune response is critical in determining the outcome of infection using Theiler's viruses with VP1 capsid protein point mutations.

Daniel's strain of Theiler's virus (DA) induces a chronic demyelinating disease in the central nervous system (CNS) of susceptible SJL mice, which serves as an excellent model of multiple sclerosis. We previously demonstrated that point mutations near a putative virus receptor-binding site [VP1 99 (Gly to Ser) or 100 (Gly to Asp)] totally attenuate the ability of DA to persist and induce demyelination in SJL mice. The current studies demonstrate that class II-restricted CD4(+) T cells play a major role in clearing VP1 mutant DA viruses from the CNS to prevent demyelination. Infection of SJL CD4((-/-)) mice with DA-VP1-99(Ser) or DA-VP1-100(Asp) resulted in virus persistence and prominent demyelination in the spinal cord. In contrast, infection of SJL CD8((-/-)) mice with DA-VP1-99(Ser) or DA-VP1-100 did not result in virus persistence or demyelination. In addition, no virus-specific cytotoxicity was observed in CNS-infiltrating lymphocytes following infection of SJL mice with VP1 mutant viruses. The mutant DA-VP1-99(Ser) and DA-VP1(100) viruses were in fact neurovirulent when compared to the wild-type DA virus, as they induced an overwhelming encephalitis and early lethality (2 to 4 days postinfection) in mice deficient in the IFN-alpha/beta receptor. Therefore, the nondemyelinating phenotype observed with DA-VP1-99(Ser) and DA-VP1-100(Asp) viruses is dependent in part on the CD4-mediated host immune response.

Amino Acid Substitution↗

PubMed2000

Post-exercise alcohol ingestion perturbs blood haemostasis during recovery.

It is known that exercise induces modification in blood haemostasis. It is, however, not known whether alcohol consumption post-exercise influences these modifications during recovery. Eleven moderately active young men were studied immediately after a standardised cycle ergometer test and during the 24-hour period of recovery. Alcohol (0. 7 g/kg body mass) was given 1 hour after exercise on one test occasion, while an equal volume of alcohol-free solution was administered on the other. Exercise induced a significant increase in factor VIII activity with a significant shortening of activated partial thromboplastin time. Parallel increases in tissue plasminogen activity and antigen with a concomitant decrease in tissue plasminogen activator inhibitor-1 activity were also observed after exercise. During recovery, while the increase in factor VIII activity post-exercise persisted in both trials, fibrinolytic activity demonstrated a sharp fall. The elevated factor VIII activity was significantly higher at 5 and 22 hours during the alcohol trial compared with the control. Although no demonstrable effect of alcohol on tissue plasminogen activator activity was present from 1 hour after ingestion onward, tissue plasminogen activator antigen and tissue plasminogen activator inhibitor-1 antigen increased significantly 22 hours following alcohol ingestion. Further comparison between trials revealed a higher plasminogen activator inhibitor-1 activity 5 hours after alcohol ingestion. In conclusion, exercise-induced changes to blood haemostasis are balanced during exercise but not during recovery. Alcohol consumption after physical exercise further perturbs blood haemostasis and could constitute a thrombotic risk.

Adult↗

PubMed2000

Molecular cloning and expression of a type-two somatostatin receptor in goldfish brain and pituitary.

Somatostatin (SRIF or SS) exerts diverse inhibitory actions through binding to specific receptors. In this study, a SRIF receptor cDNA was cloned and sequenced from goldfish brain using PCR and cDNA library screening. The cDNA encodes a 380-amino acid goldfish type-two SRIF receptor (designated as sst(2)), with seven putative transmembrane domains (TMD) and YANSCANP motif in the seventh TMD, a signature sequence for the mammalian SRIF receptor (sst) family. In addition, the amino acid sequence of the receptor has 61-62% homology to mammalian sst(2), 41-47% homology to other mammalian sst subtypes and 41-43% homology to recently identified fish sst(1) and sst(3) receptors. Both SRIF-14 and [Pro(2)]SRIF-14, two of the native goldfish SRIF forms, but not a putative goldfish SRIF-28, significantly inhibited forskolin-stimulated adenosine 3':5'-cyclic monophosphate (cAMP) release in COS-7 cells transiently expressing goldfish sst(2), suggesting functional coupling of the receptor to adenylate cyclase. None of the three peptides affected inositol phosphate production in the same receptor expression system. Northern blot showed that mRNA for the sst(2) receptor is widely distributed in goldfish brain, and highly expressed in the pituitary. The decrease in pituitary sst(2) mRNA levels following estradiol implantation suggests the presence of a negative feedback mechanism on sst(2) gene expression.

Amino Acid Sequence↗

PubMed2000

Disruption of gastrulation and heparan sulfate biosynthesis in EXT1-deficient mice.

Mutations in the EXT1 gene are responsible for human hereditary multiple exostosis type 1. The Drosophila EXT1 homologue, tout-velu, regulates Hedgehog diffusion and signaling, which play an important role in tissue patterning during both invertebrate and vertebrate development. The EXT1 protein is also required for the biosynthesis of heparan sulfate glycosaminoglycans that bind Hedgehog. In this study, we generated EXT1-deficient mice by gene targeting. EXT1 homozygous mutants fail to gastrulate and generally lack organized mesoderm and extraembryonic tissues, resulting in smaller embryos compared to normal littermates. RT-PCR analysis of markers for visceral endoderm and mesoderm development indicates the delayed and abnormal development of both of these tissues. Immunohistochemical staining revealed a visceral endoderm pattern of Indian hedgehog (Ihh) in wild-type E6.5 embryos. However, in both EXT1-deficient embryos and wild-type embryos treated with heparitinase I, Ihh failed to associate with the cells. The effect of the EXT1 deletion on heparan sulfate formation was tested by HPLC and cellular glycosyltransferase activity assays. Heparan sulfate synthesis was abolished in EXT1 -/- ES cells and decreased to less than 50% in +/- cell lines. These results indicate that EXT1 is essential for both gastrulation and heparan sulfate biosynthesis in early embryonic development.

Animals↗

PubMed2000

Enzymic characteristics of secreted aspartic proteases of Candida albicans.

Candida yeasts are rarely infectious, but frequently cause life-threatening systemic infections in patients immunocompromised by AIDS or by immunosuppressive therapeutics. The secreted aspartic proteases (Saps) are known virulence factors of pernicious Candida species. The most virulent, Candida albicans, possesses at least nine SAP genes, some of which are specifically expressed from cells with morphologies associated with virulence. Only one of these proteases, Sap2, has been previously purified from yeast in sufficient quantities for enzymic studies. The other enzymes are present in low amounts in yeast culture and are difficult to purify. As a consequence, enzyme properties, including the substrate specificities, of all Saps are poorly studied. Therefore, four Saps that are known to be expressed in C. albicans, Sap1, Sap2, Sap3 and Sap6, were produced in Escherichia coli as recombinant zymogens and purified in large quantities. These proenzymes were autoactivated and purified as active proteases. The enzymic properties including the substrate specificities at the P(1) and P(1)' sites were determined using a competitive hydrolysis method employing synthetic substrate mixtures. All four Saps cleave peptide bonds between larger hydrophobic amino acids, but these somewhat broad specificities differ in detail among the four enzymes at both sites. At the P(1) site, Sap1, Sap2 and Sap6 prefer Phe while Sap3 prefers Leu. Positively charged amino acids are also accommodated, especially by Sap2 and Sap3. The specificities at P(1)' are broader than at P(1) for all four enzymes. Sap6 prefers Ala, whereas other Saps prefer Tyr. Acidic side chains are also accommodated at this site. Analysis of substrates with a hydrophobic amino acid in P(1)' reveals that all the Saps possess a unique preference for Ala at this site. The observed differences of residue preferences among Saps may be utilized for the design of specific substrates and inhibitors.

Aspartic Acid Endopeptidases↗

PubMed2000

Sleep disordered breathing in patients with cluster headache.

OBJECTIVE: To study subjects with active or inactive cluster headache (CH) for occult sleep disordered breathing (SDB). BACKGROUND: CH frequently occurs during sleep. The authors previously found that symptoms of SDB predicted reported occurrence of CH in the first half of the night, which suggested that CH could be triggered in some cases by unrecognized SDB. METHODS: The authors performed polysomnography in 25 adults (22 men) with CH. Subjects were not selected for any sleep-related complaint. In addition to standard measures, studies included monitoring of end-tidal carbon dioxide (n = 22), and esophageal pressure (n = 20). RESULTS: The rate of apneas and hypopneas per hour of sleep was >5 in 20 subjects (80%; 95% CI, 64% to 96%), minimum oxygen saturation was <90% in 10 subjects, maximum negative esophageal pressure ranged from -13 to -65 cm H2O, and maximum end-tidal carbon dioxide was > or =50 mm Hg in eight subjects. The eight subjects with active (versus inactive) CH at the time of study had higher maximum end-tidal carbon dioxide levels (50 +/- 3 versus 44 +/- 5 mm Hg; p = 0.0007). More severe oxygen desaturation was associated with reports that CH typically occurred in the first half of the nocturnal sleep period (p = 0.008). CONCLUSIONS: SDB occurred in the majority of patients with CH. Evaluation of a patient with CH should include consideration that SDB may be present.

Adult↗