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Biomedical subjects

L Yan

Publications and source records attributed to L Yan.

At least 55 records · Page 3Linked to original sources
PubMed2001

Role of DNA methylation and histone acetylation in steroid receptor expression in breast cancer.

DNA methylation is an epigenetic modification that is associated with transcriptional silencing of gene expression in mammalian cells. Hypermethylation of the promoter CpG islands contributes to the loss of gene function of several tumor related genes, including estrogen receptor a (ER) and progesterone receptor (PR). Gene expression patterns are also heavily influenced by changes in chromatin structure during transcription. Indeed both the predominant mammalian DNA methyltransferase (DNMTI), and the histone deacetylases (HDACs) play crucial roles in maintaining transcriptionally repressive chromatin by forming suppressive complexes at replication foci. These new findings suggest that epigenetic changes might play a crucial role in gene inactivation in breast cancer. Further, inhibition of DNA methylation and histone deacetylation might be a therapeutic strategy in breast cancer, especially for those cancers with ER and PR negative phenotypes.

Acetylation↗
PubMed2001

Evidence for the involvement of phosphatidylinositol 3-kinase in fMLP-stimulated neutrophil adhesion to ICAM-1-transfected cells.

Phosphatidylinositol 3-kinase (PI-3K) controls important intracellular steps involved in inflammation, immunity, and cell growth. PI-3K also modulates leukocyte integrin adhesiveness. In this study we evaluated the role of PI-3K on neutrophil adhesion to intercellular adhesion molecule-1 (ICAM-1)-transfected cells. N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated neutrophil adhesion was inhibited by wortmannin and LY294002, two unrelated PI-3K inhibitors, whereas phorbol myristate acetate (PMA)-induced neutrophil adhesion was not inhibited by them. After fMLP stimulation, a rapid activation of AKT and ERK was observed. However, only activation of AKT was reversed by the PI-3K inhibitors. Neutrophil expression of the beta2-integrins Mac-1, lymphocyte function-associated antigen-1(LFA-1), and gp150.95 was not affected by wortmannin, nor was expression of the activation epitope recognized by MAB24. We conclude that (a) PI-3K is involved in fMLP-activated neutrophil adhesion to ICAM-1-transfected cells, (b) the mechanism involved is not mediated by the modulation of beta2-integrin expression or activation, and (c) another mechanism seems to involve the adhesion to ICAM-1 when a cellular system of adhesion is used.

3T3 Cells↗
PubMed2001

Safety, vaccine virus shedding and immunogenicity of trivalent, cold-adapted, live attenuated influenza vaccine administered to human immunodeficiency virus-infected and noninfected children.

OBJECTIVE: To assess the safety of live, attenuated influenza vaccine (LAIV) administered to relatively asymptomatic or mildly symptomatic HIV-infected children and non-HIV-infected children. METHODS: Twenty-five non-HIV and 24 HIV-infected children (CDC Class N or A1,2) were enrolled into this double blind, placebo-controlled study. Children were randomized within each HIV status group to one of two dosing regimens: Regimen 1, Dose 1 = LAIV, Dose 2 = placebo, Dose 3 = LAIV; or Regimen 2, Dose 1 = placebo, Dose 2 = LAIV, Dose 3 = LAIV. Study doses were separated by 28 to 35 days. Reactogenicity events within 10 days and adverse events within 28 to 35 days after each study dose were recorded. Blood HIV RNA concentrations, CD4 counts and CD4% were measured throughout the study on HIV-infected children. Quantitative influenza cultures were performed on nasal aspirates collected periodically from all children up to 28 to 35 days after each study dose. Influenza isolates were assessed for retention of the temperature-sensitive phenotype. Serum influenza HAI antibodies were measured before and after each LAIV vaccination. RESULTS: No significant differences were found in rates of reactogenicity events and vaccine-related adverse events after placebo or the first dose of LAIV within each HIV status group, nor were differences found between HIV-infected and HIV-uninfected children after each dose of LAIV. Overall none of the HIV-infected children experienced a significant LAIV-related serious adverse event or influenza-like illness, making the one sided 95% CI of such a serious event occurring after LAIV 0 to 12%. No significant changes in geometric mean HIV RNA concentrations, CD4 counts or CD4% or prolonged or increased quantity of LAIV virus shedding occurred in HIV-infected children after receiving either dose of LAIV. All recovered influenza isolates retained the temperature-sensitive phenotype. After two doses of LAIV, 83% of the non-HIV-infected and 77% of the HIV-infected children had a > or = 4-fold rise in influenza antibody to at least one of the three LAIV strains. CONCLUSION: If relatively healthy HIV-infected children become exposed to LAIV inadvertently, then serious adverse outcomes would not be expected to occur frequently.

Child↗
PubMed2001

Comparative sequence analysis of colinear barley and rice bacterial artificial chromosomes.

Colinearity of a large region from barley (Hordeum vulgare) chromosome 5H and rice (Oryza sativa) chromosome 3 has been demonstrated by mapping of several common restriction fragment-length polymorphism clones on both regions. One of these clones, WG644, was hybridized to rice and barley bacterial artificial chromosome (BAC) libraries to select homologous clones. One BAC from each species with the largest overlapping segment was selected by fingerprinting and blot hybridization with three additional restriction fragment-length polymorphism clones. The complete barley BAC 635P2 and a 50-kb segment of the rice BAC 36I5 were completely sequenced. A comparison of the rice and barley DNA sequences revealed the presence of four conserved regions, containing four predicted genes. The four genes are in the same orientation in rice, but the second gene is in inverted orientation in barley. The fourth gene is duplicated in tandem in barley but not in rice. Comparison of the homeologous barley and rice sequences assisted the gene identification process and helped determine individual gene structures. General gene structure (exon number, size, and location) was largely conserved between rice and barley and to a lesser extent with homologous genes in Arabidopsis. Colinearity of these four genes is not conserved in Arabidopsis compared with the two grass species. Extensive similarity was not found between the rice and barley sequences other than within the exons of the structural genes, and short stretches of homology in the promoters and 3' untranslated regions. The larger distances between the first three genes in barley compared with rice are explained by the insertion of different transposable retroelements.

Arabidopsis↗
PubMed2001

Fish monocytes as a model for mycobacterial host-pathogen interactions.

Mycobacterium marinum, a relatively rapid-growing fish and human pathogen, has become an important model for the investigation of mycobacterial pathogenesis. M. marinum is closely related to the Mycobacterium tuberculosis complex and causes a disease in fish and amphibians with pathology similar to tuberculosis. We have developed an in vitro model for the study of M. marinum virulence mechanisms using the carp monocytic cell line CLC (carp leukocyte culture). We found that fish monocytes can differentiate between pathogenic and nonpathogenic mycobacterial species. Interestingly, M. marinum enters fish monocytes at a 40- to 60-fold-higher rate than Mycobacterium smegmatis. In addition, M. marinum survives and replicates in fish monocytes while M. smegmatis is killed. We also found that M. marinum inhibits lysosomal fusion in fish monocytes, indicating that these cells may be used to dissect the mechanisms of intracellular trafficking in mycobacteria. We conclude from these observations that monocytic cells from fish, a natural host for M. marinum, provide an extremely valuable model for the identification and characterization of mycobacterial virulence determinants in the laboratory.

Animals↗
PubMed2001

Blockade of caspases inhibits amebic liver abscess formation in a mouse model of disease.

We looked at the effect of inhibiting caspases on amebic liver abscess in the mouse model of infection. A dose of the pan-caspase inhibitor benzyloxycarbonyl-V-A-D-O-methyl fluoromethyl ketone (Z-VAD-FMK; R & D Systems) given to SCID mice 2 h prior to direct hepatic inoculation with Entamoeba histolytica trophozoites, and 12 h after amebic inoculation, reduced the mean liver abscess size by 70% at 24 h compared to a control group. These data indicate that apoptosis plays a significant but not an exclusive role in amebic liver abscess formation in the mouse model.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Characterization of waxy proteins and waxy genes of Triticum timopheevii and T. zhukovskyi and implications for evolution of wheat.

The granule-bound starch (GBSS I, waxy protein) in Triticum timopheevii (AtAtGG) and T. zhukovskyi (AtAtAzAzGG) and a diagnostic section of the genes encoding GBSS-I from the Wx-TtA and Wx-G loci of T. timopheevii and the Wx-TtA, Wx-G, and Wx-TzA loci of T. zhukovskyi were investigated in this study. The waxy proteins in these two polyploid wheats could not be separated into distinct bands, in contrast to those in the T. turgidum (AABB)-T. aestivum (AABBDD) lineage. Alignment of sequences of the section covering exon4-intron4-exon5 of the various waxy genes led to the identification of gene-specific sequences in intron 4. The sequences specific to the Wx-TtA and Wx-G genes of T. timopheevii were different from those of the Wx-A1 gene and Wx-B1 genes of T. turgidum and T. aestivum. A surprising observation was that the Wx-TzA of T. zhukovskyi did not match with the Wx-TmA of T. monococcum, a putative donor of the Az genome, but matched unexpectedly and perfectly with the Wx-B1 gene on chromosome 4A, which is proposed to have translocated from the chromosome 7B of T. aestivum. The possible genetic mechanism explaining these observations is discussed.

Base Sequence↗
PubMed2001

Nitric oxide and cGMP protein kinase activity in aged ventricular myocytes.

We tested the hypothesis that nitric oxide-induced negative functional effects through cGMP would be reduced in aged cardiac myocytes. Maximum rate of shortening (R(max)) and percent shortening of ventricular myocytes from young (6 mo) and old (3 y) rabbits were studied using a video edge detector. cGMP-dependent phosphorylation was examined by electrophoresis and autoradiography. Myocytes received a nitric oxide donor S-nitroso-N-acetyl-penicillamine (SNAP, 10(-7), 10(-6), and 10(-5) M) followed by KT-5823 (10(-6) M), a cGMP protein kinase inhibitor. Baseline function was similar in young and old myocytes (89.1 +/- 4.5 young vs. 86.4 +/- 8.3 microm/s old R(max), 5.6 +/- 0.3 vs. 5.2 +/- 0.7%shortening). SNAP (10(-5) M) decreased R(max) in both young (25%, n = 6) and old myocytes (24%, n = 7). SNAP also reduced percent shortening by 28% in young and 23% in old myocytes. The negative effects of SNAP were partially reversed by KT-5823 only in young myocytes. Multiple proteins were phosphorylated by cGMP, and KT-5823 could reduce this effect. The degree of phosphorylation was significantly less in old myocytes. These results suggest that the functional response of ventricular myocytes to nitric oxide was preserved during aging. However, the importance of cGMP-dependent protein phosphorylation was decreased, indicating a shift to other pathways.

Aging↗
PubMed2001

Morphology and current-voltage characteristics of nanostructured pentacene thin films probed by atomic force microscopy.

Atomic force microscopy was used to study the growth modes (on SiO2, MoS2, and Au substrates) and the current-voltage (I-V) characteristics of organic semiconductor pentacene. Pentacene films grow on SiO2 substrate in a layer-by-layer manner with full coverage at an average thickness of 20 A and have the highest degree of molecular ordering with large dendritic grains among the pentacene films deposited on the three different substrates. Films grown on MoS2 substrate reveal two different growth modes, snowflake-like growth and granular growth, both of which seem to compete with each other. On the other hand, films deposited on Au substrate show granular structure for thinner coverages (no crystal structure) and dendritic growth for higher coverages (crystal structure). I-V measurements were performed with a platinum tip on a pentacene film deposited on a Au substrate. The I-V curves on pentacene film reveal symmetric tunneling type character. The field dependence of the current indicates that the main transport mechanism at high field intensities is hopping (Poole-Frenkel effect). From these measurements, we have estimated a field lowering coefficient of 9.77 x 10(-6) V-1/2 m1/2 and an ideality factor of 18 for pentacene.

Crystallization↗
PubMed2001

Cost-effectiveness analysis of an intranasal influenza vaccine for the prevention of influenza in healthy children.

OBJECTIVE: Intranasal influenza vaccine has proven clinical efficacy and may be better tolerated by young children and their families than an injectable vaccine. This study determined the potential cost-effectiveness (CE) of an intranasal influenza vaccine among healthy children. METHODS: We conducted a CE analysis of data collected between 1996 and 1998 during a prospective 2-year efficacy trial of intranasal influenza vaccine, supplemented with data from the literature. The CE analysis included both direct and indirect costs. We enrolled 1602 healthy children aged 15 to 71 months in year 1, 1358 of whom were enrolled in year 2. One or 2 doses of intranasal influenza vaccine or placebo were administered to measure the cost per febrile influenza-like illness (ILI) day avoided. RESULTS: During the 2-year study period, vaccinated children had an average of 1.2 fewer ILI fever days/child than unvaccinated children. In an individual-based vaccine delivery scenario with vaccine given twice in the first year and once each year thereafter at an assumed base case total cost of $20 for the vaccine and its administration (ie, per dose), CE was approximately $30/febrile ILI day avoided. CE ranged from $10 to $69/febrile ILI day avoided at $10 to $40/dose, respectively. In a group-based delivery scenario, vaccination was cost saving compared with placebo and remained so if vaccine cost was <$28 (the break-even price per dose). In the individual-based scenario, vaccination was cost saving if vaccine cost was <$5. In this scenario, nearly half of lost productivity in the vaccine group was attributable to vaccine visits, which overshadowed the relatively modest savings in ILI-associated costs averted. CONCLUSIONS: Routine use of intranasal influenza vaccine among healthy children may be cost-effective and may be maximized by using group-based vaccination approaches. cost-effectiveness, influenza, vaccine, children.

Administration, Intranasal↗
PubMed2001

DNA methylation in breast cancer.

Like all cancers, breast cancer is considered to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumor suppressor loss. More recently, the role of epigenetic change as a distinct and crucial mechanism to silence a variety of methylated tissue-specific and imprinted genes has emerged in many cancer types. This review will briefly discuss basic aspects of DNA methylation, recent advances in DNA methyltransferases, the role of altered chromatin organization and the concept of gene transcriptional regulation built on methylated CpGs. In particular, we discuss epigenetic regulation of certain critical tumor suppressor and growth regulatory genes implicated in breast cancer, and its relevance to breast cancer diagnosis, prognosis, progression and therapy.

Animals↗
PubMed2001

[Applied anatomy of the sensate latissimus dorsal muscular flap with the lateral posterior branch of the intercostal nerve].

OBJECTIVE: To provide anatomy basis for a free latissimus dorsal muscular flap with the sensate nerve. METHODS: The structure of back and lateral chest area were dissected and the origin, alignment and distribution of the intercostals nerve within the area of latissimus dorsal muscular flap were observed in 40 adult cadaver specimens. RESULTS: The 5th to 10th lateral posterior branches of the thoracic nerve pierced from respective intercostal area near the axial anterior line and run a long distance in deep fascia. They distributed mainly in lateral latissimus skin outside the scapular line and anastomosed with the lower branch near the scapular line. Among these branchs, the 6th to 8th branches had a longer nerve distribution respectively and the pedicle of nerve and artery was parallel and long. CONCLUSION: It is possible to design a sensate latissimus dorsal muscular flap with the 6th to 8th lateral posterior branch of the intercostal nerve.

Adult↗
PubMed2001

[Structure and function of pancreatic microcirculation].

To gain an insight into the relationship between structure and function in pancreatic microcirculation, observations were carried out in 9 corpse, 30 monkeys, 24 dogs, 62 Wistar rats and 24 rabbits by the use of scanning electron microscopy and light microscopy with the technique of retaining microcirculatory dynamic and tissular information in the static specimens, and/or by intravital fluorescence microscopy with FITC-labeled erythrocytes. The results showed: there were two capillary beds destined for the endocrine and exocrine parts of pancreas between the intralobular arteriole and venule; the blood of pancreatic portal circulation flowed from the endocrine to the exocrine part; each pancreatic lobule was supplied by a single centrally located intralobular artery and there was no anastomosis between the intralobular arterioles or any of their branches, so they were end arteries; the physiological blood flow was about 1.18 +/- 0.05 nl/min per capillary with stable capillary perfusion pattern; a profound decreased functional capillary density and capillary perfusion was observed in the early phase of acute pancreatitis. These results suggest that pancreatic lobule is a structured and functional basic unit of pancreatic microcirculation, insulo-acinar portal circulation represents the basic feature of the pancreatic microcirculation, and the intralobular arteriole, being an end artery, forms the anatomical basis of the pancreatic microcirculatory disturbance during acute pancreatitis.

Adult↗
PubMed2001

Clinical study on treatment of senile vascular dementia by acupuncture.

63 patients with senile vascular dementia were randomly divided into the treatment group (treated by acupuncture) and the control group (treated with piracetam). The authors observed the changes in the score of Hasegawa's dementia scale (HDS), p300, rheoencephalogram, topographic EEG, superoxide dismutase (SOD) activity in erythrocytes, and lipid peroxide (LPO) level in plasma before and after treatment. The statistical data showed that the total effective rate in the treatment group (80.6%) was significantly higher than that in the control group (25%), and the differences in the observed indexes before and after treatment were significant (P < 0.05 or P < 0.01) in the treatment group but not in the control group (P > 0.05), indicating that the acupuncture treatment was superior in immediate therapeutic effect on senile vascular dementia to drug treatment.

Acupuncture Therapy↗
PubMed2001

Immune privilege induced by cotransplantation of islet and allogeneic testicular cells.

OBJECTIVE: To induce islet allograft long-term survival through cotransplantation of islet cells with sertoli cells. METHODS: Testicular sertoli cells were prepared by digestion with collagenase, trypsin and DNase, and were cultured for 48 hours. Collagenase digested and Ficoll purified donor (Wistar rat) islets were cotransplanted with allogeneic sertoli cells in the absence of systemic immunosuppression. Terminal deoxynucleotidyl transferase-mediated X-dUTP nick-end labeling (TUNEL) was used to label apoptosis of lymphocytes surrounding the islet graft. RESULTS: Cotransplantation of islets and 1 x 10(7) sertoli cells reversed the diabetic state for more than 60 days in 100% (6/6) of the chemically diabetic Sprague Dawley rats. Grafts consisting of islets alone or islets plus 1 x 10(5) sertoli cells survived only for 5-6 days. Apoptosis of lymphocytes surrounding the islets was quite clear. CONCLUSION: Cotransplantation of islets with FasL+ sertoli cells induces local immune privilege and allows long-term graft survival without systemic immunosuppression.

Animals↗
PubMed2001

The cAMP-mediated protein kinase signal transduction pathway is involved in the pyrogenic effect of CRH in rats.

OBJECTIVE: To determine whether the cyclic adenosine monophosphate (cAMP) mediated protein kinase signal transduction pathway is involved in the pyrogenic action of corticotropin releasing hormone (CRH) in rats. METHODS: Corticotropin releasing hormone, 2',3'-dideoxyadenosine (DDA) and adenosine-3',5'-(cyclic) monophosphorothionate, Rp-Isomer (Rp-cAMPS), were administered intracerebroventricularly (i.c.v.). The colonic temperature was measured using a thermistor, and the content of cAMP in the hypothalamus was determined by radioimmunoassay. Hypothalamic incubation was used to assess the effects of CRH on the content of cAMP in the hypothalamus in vitro. RESULTS: Microinjection (i.c.v.) of CRH (2.5 micrograms, 5.0 micrograms and 10 micrograms) caused increases in colonic temperature and the hypothalamus cAMP level in conscious rats. CRH increased hypothalamus cAMP level in vitro. The pyrogenic effects of CRH were abolished or markedly inhibited by prior injection (i.c.v.) of an adenylate cyclase inhibitor, DDA (30 micrograms), or an inhibitor of cAMP-dependent protein kinase, Rp-cAMPS (15 micrograms). CONCLUSION: cAMP mediates the pyrogenic action of centrally administered of CRH in rats, and protein kinase A may play an important role in the central CRH-induced fever. The cAMP-dependent protein kinase signal transduction pathway may be involved in the central mechanisms of the pyrogenic action of CRH in rats.

Animals↗
PubMed2001

Relationship of large multifunctional proteasome 7 gene polymorphism with susceptibility to type 1 diabetes mellitus and DR3 gene.

OBJECTIVE: To study the relationship of the large multifunctional proteasome 7 (LMP7) gene polymorphism with susceptibility to type 1 diabetes mellitus (DM-1) and the DR3 gene in south Chinese Han population. METHODS: LMP7 genotypes and the DR3 gene were identified in 71 DM-1 patients and 86 healthy persons (as controls) by polymerase chain reaction-restriction fragment length polymorphism. DM-1 patients and controls were divided into DR3-positive and DR3-negative subjects. The frequencies of LMP7 genotypes and alleles were compared between DM-1 patients and controls respectively in the random subjects and in the DR3-matched subjects. Furthermore, DM-1 patients were divided into 3 groups according to the age of diabetic onset: group A < or = 14 years, group B 15-30 years, group C > or = 31 years. RESULTS: In the random subjects, the frequency of LMP7-B/B was lower (39% vs 58%, P < 0.05) and that of LMP7-B/A was higher (54% vs 31%, P < 0.01) in DM-1 patients than that in controls. In DR3-positive subjects, the frequencies of LMP7 genotypes and alleles showed no differences between DM-1 patients and controls. In DR3-negative subjects, the frequency of LMP7-B/B was decreased (40% vs 61%) and that of LMP7-B/A was increased (55% vs 28%, P < 0.01) in DM-1 patients. The frequencies of LMP7 genotypes and alleles showed no significant differences among different ages of diabetic onset. CONCLUSIONS: LMP7-B/B may be the protective genotype, and LMP7-B/A may be the susceptible genotype of DM-1, and this may not be affected by the DR3 gene. Persons with LMP7-B/B may have a decreased risk, and those with LMP7-B/A have an increased risk suffering from DM-1. The LMP7 gene may not be associated with the age of diabetic onset.

Adolescent↗