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Biomedical subjects

J Song

Publications and source records attributed to J Song.

At least 73 records · Page 4Linked to original sources
PubMed2001

Identification of mouse Jun dimerization protein 2 as a novel repressor of ATF-2.

A mouse cDNA that encodes a DNA-binding protein was identified by yeast two-hybrid screening, using activating transcription factor-2 (ATF-2) as the bait. The protein contained a bZIP (basic amino acid-leucine zipper region) domain and its amino acid sequence was almost identical to that of rat Jun dimerization protein 2 (JDP2). Mouse JDP2 interacted with ATF-2 both in vitro and in vivo via its bZIP domain. It was encoded by a single gene and various transcripts were expressed in all tested tissues of adult mice, as well as in embryos, albeit at different levels in various tissues. Furthermore, mouse JDP2 bound to the cAMP-response element (CRE) as a homodimer or as a heterodimer with ATF-2, and repressed CRE-dependent transcription that was mediated by ATF-2. JDP2 was identified as a novel repressor protein that affects ATF-2-mediated transcription.

3T3 Cells↗
PubMed2001

Arthritis prevalence and activity limitations in older adults.

OBJECTIVE: To evaluate the prevalence of arthritis and activity limitations among older Americans by assessing their demographic, ethnic, and economic characteristics. METHODS: Data from the Asset and Health Dynamic Survey Among the Oldest Old (AHEAD), a national probability sample of community-dwelling adults born before 1924, were analyzed cross-sectionally. Arthritis that resulted in a physician's visit or a joint replacement not associated with a hip fracture was ascertained by self-report. RESULTS: The prevalence of arthritis in older adults ranged from 25% in non-Hispanic whites to 40% in non-Hispanic blacks to 44% in Hispanics. A higher prevalence of arthritis was associated with less education as well as lower income and less wealth. The prevalence of limitations in activities of daily living (ADL) among non-Hispanic white, non-Hispanic black, and Hispanic adults who reported arthritis only was 29%, 30%, and 37%, respectively, and increased to 48%, 57%, and 56%, respectively, among those reporting arthritis plus other chronic conditions, after adjustment for age and sex. CONCLUSION: Non-Hispanic black and Hispanic older adults reported having arthritis at a substantially higher frequency than did non-Hispanic whites. In addition, Hispanics reported higher rates of ADL limitations than did non-Hispanic whites with comparable disease burden. Further study is needed to confirm and elucidate the reasons for these racial and economic disparities in older populations.

Activities of Daily Living↗
PubMed2001

Oligoclonal B lymphocyte expansion in the synovium of a patient with Behçet's disease.

OBJECTIVE: Plasma cell infiltration is observed in recurrent arthritis associated with Behçet's disease (BD). The immune mechanism underlying B lymphocyte proliferation in the synovium is unclear. One hypothesis involves nonspecific polyclonal activation and another involves antigen-driven activation. The present study was undertaken to test both hypotheses and identify immunoglobulin genes that are clonally expanded in the synovium. METHODS: Peripheral blood lymphocytes (PBL) and synovial cells from a patient with BD and PBL from a healthy control subject were obtained. Complementarity-determining region 3 (CDR3) fingerprinting analysis and nucleotide sequence analysis of Ig transcripts derived from clonally expanded B lymphocytes were performed in parallel. RESULTS: Of 44 mu heavy chain clones of the VH4 family identified in the synovial tissue from the BD patient, 8 clones showed identical nucleotide sequences, and therefore, 18.2% were clonally expanded. For y heavy chain, 4 of 50 clones of the VH3 family showed nearly identical sequences; therefore, 4-8% were clonally expanded. The kappa light chain did not show a dominant band, but a clone with a 12-amino acid CDR3 showed 3% clonal expansion. Somatic mutations were frequently observed, with a high ratio of replacement to silent mutations in the CDRs compared with the framework regions. Three Ig genes expressed in the clonally expanded B lymphocytes were derived from germline gene segments reported to be involved in the production of autoantibodies. CONCLUSION: These results support the hypothesis that antigen-driven clonal B lymphocyte proliferation occurs in the synovium in BD. Immunoglobulin transcripts clonally expanded in the synovium were identified.

Adult↗
PubMed2001

Vascular smooth muscle cell phenotypic modulation in culture is associated with reorganisation of contractile and cytoskeletal proteins.

Smooth muscle cells (SMC) exhibit a functional plasticity, modulating from the mature phenotype in which the primary function is contraction, to a less differentiated state with increased capacities for motility, protein synthesis, and proliferation. The present study determined, using Western analysis, double-label immunofluorescence and confocal microscopy, whether changes in phenotypic expression of rabbit aortic SMC in culture could be correlated with alterations in expression and distribution of structural proteins. "Contractile" state SMC (days 1 and 3 of primary culture) showed distinct sorting of proteins into subcellular domains, consistent with the theory that the SMC structural machinery is compartmentalised within the cell. Proteins specialised for contraction (alpha-SM actin, SM-MHC, and calponin) were highly expressed in these cells and concentrated in the upper central region of the cell. Vimentin was confined to the body of the cell, providing support for the contractile apparatus but not co-localising with it. In line with its role in cell attachment and motility, beta-NM actin was localised to the cell periphery and basal cortex. The dense body protein alpha-actinin was concentrated at the cell periphery, possibly stabilising both contractile and motile apparatus. Vinculin-containing focal adhesions were well developed, indicating the cells' strong adhesion to substrate. In "synthetic" state SMC (passages 2-3 of culture), there was decreased expression of contractile and adhesion (vinculin) proteins with a concomitant increase in cytoskeletal proteins (beta-non-muscle [NM] actin and vimentin). These quantitative changes in structural proteins were associated with dramatic changes in their distribution. The distinct compartmentalisation of structural proteins observed in "contractile" state SMC was no longer obvious, with proteins more evenly distributed throughout the cytoplasm to accommodate altered cell function. Thus, SMC phenotypic modulation involves not only quantitative changes in contractile and cytoskeletal proteins, but also reorganisation of these proteins. Since the cytoskeleton acts as a spatial regulator of intracellular signalling, reorganisation of the cytoskeleton may lead to realignment of signalling molecules, which, in turn, may mediate the changes in function associated with SMC phenotypic modulation.

Actinin↗
PubMed2001

Reorganization of structural proteins in vascular smooth muscle cells grown in collagen gel and basement membrane matrices (Matrigel): a comparison with their in situ counterparts.

When smooth muscle cells are enzyme-dispersed from tissues they lose their original filament architecture and extracellular matrix surrounds. They then reorganize their structural proteins to accommodate a 2-D growth environment when seeded onto culture dishes. The aim of the present study was to determine the expression and reorganization of the structural proteins in rabbit aortic smooth muscle cells seeded into 3-D collagen gel and Matrigel (a basement membrane matrix). It was shown that smooth muscle cells seeded in both gels gradually reorganize their structural proteins into an architecture similar to that of their in vivo counterparts. At the same time, a gradual decrease in levels of smooth muscle-specific contractile proteins (mainly smooth muscle myosin heavy chain-2) and an increase in beta-nonmuscle actin occur, independent of both cell growth and extracellular matrix components. Thus, smooth muscle cells in 3-D extracellular matrix culture and in vivo have a similar filament architecture in which the contractile proteins such as actin, myosin, and alpha-actinin are organized into longitudinally arranged "myofibrils" and the vimentin-containing intermediate filaments form a meshed cytoskeletal network. However, the myofibrils reorganized in vitro contain less smooth muscle-specific and more nonmuscle contractile proteins.

Actinin↗
PubMed2001

Cytoskeletal reorganization during the formation of oligodendrocyte processes and branches.

During oligodendrocyte development, signals relevant to process formation must be transduced into appropriate changes in cytoskeletal organization. We have explored how microtubules and microfilaments interact during the outgrowth and branching of oligodendrocyte processes in culture. We observed that microfilaments are enriched in the peripheral region beneath the plasma membrane and constitute the major cytoskeletal element at the leading edge of the process, which is also enriched in the B-isoform of the non-muscle myosin II heavy chain. Microtubules form a dense bundle within the process and splay before extending into the leading edge and branches, following tracks laid by microfilaments. Pharmacologic disruption of microfilaments and microtubules compromised normal process outgrowth and branching. However, microtubules rapidly reinvaded most processes after removal of both antimicrotubule and antimicrofilament drugs, but the reinvasion was severely compromised if the antimicrofilament drug was retained. These results are consistent with the hypothesis that microfilaments guide the local reorganization of microtubules for the elongation of oligodendrocyte processes and the formation of new branches.

Actin Cytoskeleton↗
PubMed2001

Genetic variation of the methylenetetrahydrofolate reductase and cystathionine beta-synthase genes in Korean patients with coronary artery disease and a new polymorphism in intron 7.

We investigated polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) genes in Korean patients with coronary artery disease (CAD) and identified a new polymorphism (c-->t) in intron 7 of the CBS gene using the single-strand conformation polymorphism method. No significant differences were found in allele frequencies for either gene between the CAD and normal groups although the frequency of the so-called thermolabile MTHFR polymorphism, a proposed risk factor for CAD, was higher in Koreans than in other populations studied. The relatively low incidence of CAD in Korea suggests that this MTHFR polymorphism is not causative in this population.

Coronary Disease↗
PubMed2001

Ligustrazini inhibits endotoxin induced PAI-1 expression in human umbilical vein endothelial cells.

Plasminogen activator inhibitor 1 (PAI-1) is one of important coagulant factors. Endotoxin lipopolysaccharide (LPS) induces thrombosis by stimulating PAI-1 secretion of vascular cells (EC). Using sandwich enzyme-linked immunosorbent assay (ELISA) and Northern blot, was investigated the effects of Chinese medicine ligustrazini on PAI-1 expression in EC and LPS-stimulated EC. The results showed that ligustrazini inhibited both basal and LPS-induced PAI-1 mRNA expression in EC. The effect of ligustrazini on LPS-induced PAI-1 secretion worked in a dose-dependent manner. This study provided theoretic and experimental evidence for use of ligustrazini against septic shock and cardiovascular diseases.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Effect of directional switching frequency on toluene degradation in a vapor-phase bioreactor.

A potential method to improve biomass distribution and the stability of vapor-phase bioreactors is to operate them in a directionally switching mode such that the contaminant air stream direction is periodically reversed through the reactor. In this study, the effect of switching frequency (SF) on bioreactor performance and biodegradation activity was investigated at 1-, 3- and 7-day SFs using toluene as a model compound. Rapid losses of biodegradation capacity and serious bioreactor instability were observed in the bioreactor operated at a 1-day SF. It is hypothesized that the frequent dynamic loading conditions at the 1-day SF hindered biofilm development and ultimately bioreactor stability. In contrast, bioreactors operated at the 3- and 7-day SFs achieved overall removal efficiencies of greater than 99% for 72 and 59 days of operation, respectively. Following each air-stream reversal, the bioreactor operated at the 7-day SF required 48 h to fully restore biodegradation capacity in the inlet bioreactor section. The 1-day SF bioreactor required no such reacclimation period. The toluene-degrading activity in the inlet section of the 7-day SF bioreactor dropped by 71% during the 7-day cycle, whereas it decreased by only 11% in the inlet of the 3-day SF bioreactor. These declines suggest that continuous or near-continuous exposure to toluene can inhibit microbial activity. Of the three SFs examined, the 3-day SF yielded the most efficient bioreactor performance by balancing reacclimation requirements with biodegradation activity losses.

Bacteria↗
PubMed2001

A phase I/IIa study on intra-articular injection of holmium-166-chitosan complex for the treatment of knee synovitis of rheumatoid arthritis.

Previous animal studies have established that the intra-articular injection of holmium-166-chitosan complex (DW-166HC) causes effective necrosis of the inflamed synovium with litle leakage of radioactivity from the injected joint. Based on these findings, we conducted a phase I/IIa study to examine the biodistribution of DW-166HC and to assess the safety of DW-166HC for the treatment of knee synovitis in patients with rheumatoid arthritis (RA). A total of 16 patients [1 man, 15 women; median age 49 (range 36-65) years] who had RA knee synovitis refractory to disease-modifying anti-rheumatic drug treatments of > 3 months' duration were randomly assigned to three treatment groups with different radiation doses of DW-166HC: 370 MBq (n = 6), 555 MBq (n = 5) and 740 MBq (n = 5). In each treatment group, blood and urine radioactivity were analysed by beta counter and biodistribution of the injected DW-166HC was evaluated using a gamma scan camera. Clinical assessment was done according to three variables (evaluation method): knee joint pain (visual analogue scale), range of motion (goniometry) and joint swelling (circumference of knee joint). The duration of follow-up observation was 3 months. Following the intra-articular injection of DW-166HC, the blood radioactivity was little changed from the baseline measurement and the accumulated radioactivity excreted in urine was minimal. Gamma scan study indicated that most of the injected radiochemical was localized within the injected joint cavity, and the extra-articular leakage was negligible at 24 h after the injection: brain, 0.3%; lung, 0.6%; abdomen, 0.7%; and pelvis, 0.8%. Major adverse events were transient post-injection knee joint pain and swelling. These results suggest that DW-166HC might be a safe agent for radiation synovectomy, particularly for the treatment of knee synovitis of RA, and further trials in a larger patient population are warranted to evaluate the therapeutic efficacy of DW-166HC.

Adult↗
PubMed2001

Further characterization of the sixth transmembrane domain of Pgp1 by site-directed mutagenesis.

PURPOSE: Several studies have identified amino acid residues located on the hydrophobic side of the helix that forms transmembrane domain 6 (TM6) of the ABC transporter P-glycoprotein (Pgp) as being important for function. The purpose of this study was to determine if alterations to residues on the hydrophilic side could also affect function and to determine the extent to which altering the hydrophobic nature of residues on the hydrophobic side would impair the protein. METHODS: A full-length cDNA encoding wild-type Pgp1 from CHL cells was used as a template for site-directed mutagenesis. Eight different mutations, three on the hydrophilic side and five on the hydrophobic side, were prepared and transfected into drug-sensitive host cells. Wild-type transfectants served as controls. Drug resistance levels, RD50 values for cyclosporin A (CsA) and verapamil, iodoarylazidoprazosin (IAAP) photolabeling and verapamil-stimulated ATPase activity were evaluated. RESULTS: Substitution of any one of three amino acid residues on the hydrophilic side of TM6 disrupted function and led to alterations in drug resistance, CsA sensitivity, IAAP photoaffinity labeling, and in one case verapamil-stimulated ATPase activity. Replacement of a hydrophobic residue on the hydrophobic face of the helix with increasingly hydrophilic side-chains led to functional changes, the extent of which did not correlate with the degree of side-chain hydrophilicity. Finally, while the placement of a proline residue along either face of the helix had varying effects on function, in all cases its presence interfered with verapamil-stimulated ATPase activity. CONCLUSIONS: Taken together these results indicate that both faces of TM6 mediate Pgp1 function and that the expected conformational changes resulting from proline substitutions at a variety of locations within the helix can alter the protein's enzymatic activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Genetic variations of the paraoxonase gene in patients with coronary artery disease.

OBJECTIVES: Paraoxonase (PON) plays an important role in preventing low density lipoprotein (LDL) oxidation and thus may be involved in protection against atherosclerosis. Several studies have suggested that genetic variations of the PON gene are associated with plasma HDL levels and coronary artery disease (CAD). This study was conducted to elucidate the association between three polymorphisms of the PON1 and PON2 genes and Korean patients with CAD. DESIGN AND METHODS: One hundred ninety-one patients with CAD and 113 age-matched normal controls were examined by polymerase chain reaction (PCR). The PCR products were analyzed for PON polymorphisms by restriction enzyme digestion. RESULTS: There was linkage disequilibria between each polymorphism pair in the CAD and control groups. The Hsp92II polymorphism at codon 54 of the PON1 gene was positively associated with HDL-cholesterol levels in the control group (p = 0.02). An association between the AlwI polymorphism and HDL-cholesterol level appeared statistically significant in women of the normal group (p = 0.04). In addition, the DdeI and AlwI polymorphisms were positively associated with HDL (p = 0.02) and LDL (p = 0.03) levels in men of the CAD group, respectively. CONCLUSIONS: Our study suggested a gene-gene interaction between the PON1 and PON2 polymorphisms for CAD risk. However, we could not exclude the possibility that these polymorphisms may have linkage disequilibrium with a tightly linked PON3 locus or significant atherosclerotic alleles of nearby genes. Family studies may, therefore, help to confirm the role of the PON polymorphism for CAD risk.

Adult↗
PubMed2001

Correlation of plasma homocysteine and mitochondrial DNA content in peripheral blood in healthy women.

Hyperhomocysteinemia is an independent risk factor of cardiovascular disease and associated with insulin resistance, although their causal relationship remains unclear. A previous report has shown that high concentration of homocysteine damages mitochondrial gene expression, function and structure. As we found recently, the mitochondrial DNA (mtDNA) contents are inversely correlated with insulin resistance parameters. Thus there is possibility that plasma total homocysteine (tHcy) level is somewhat correlated with mtDNA content. Sixty healthy women (mean age 40.3+/-20.9 yr, range 18-78 yr) were recruited to investigate the correlation of plasma tHcy level and mtDNA content in peripheral blood. A significant negative correlation was found between plasma tHcy levels and mtDNA content (r=-0.507, P<0.01). Plasma tHcy and mtDNA content have an independent effect on each other and on insulin resistance (HOMA-insulin resistance (IR) score) respectively in multiple regression model. Plasma tHcy showed positive correlations with age (r=0.407), W/H ratio (r=0.370), total cholesterol (r=0.338), LDL-cholesterol (r=0.317) and insulin resistance (HOMA-IR score) (r=0.261); and a negative correlation with folate (r=-0.273). MtDNA content showed negative correlations with age (r=-0.407), BMI (r=-0.440), W/H ratio (r=-0.659), SBP (r=-0.350), total cholesterol (r=-0.340), triglyceride (r=-0.376), LDL-cholesterol (r=-0.349), fasting plasma insulin (r=-0.483), and insulin resistance (HOMA-IR score) (r=-0.423); and a positive correlation with folate (r=0.299). In this study, there was a significant inverse correlation between plasma tHcy level and mtDNA content. Further study will be warranted to elucidate the mechanism by which two factors are associated.

Adolescent↗
PubMed2001

Word fluency in relation to severity of closed head injury, associated frontal brain lesions, and age at injury in children.

Effects of closed head injury (CHI) severity, focal brain lesions, and age at injury on word fluency (WF) were studied longitudinally in 122 children (78 severe, 44 mild); 112 CHI patients (68 severe, 44 mild CHI) and 104 uninjured normal controls participated in a cross-sectional study. WF was measured by asking the child to generate as many words as possible beginning with a designated letter within 60 s, repeated for three letters. Intellectual ability, receptive vocabulary, narrative discourse, and word list recall were also measured. Results of the cross-sectional study showed a significant group effect with poorer WF in severe CHI than mild CHI and control groups. Growth curve analysis of longitudinal data revealed an interaction of age, follow-up interval, and CHI severity as WF recovery was slower after severe CHI in younger children as compared to severe CHI in older children or mild CHI in younger children. An interaction of left frontal lesion with age and interval indicated a more adverse effect on WF in older children. Right frontal lesion effect was nonsignificant and did not interact with age. Correlations of WF with receptive vocabulary, word list recall, and narrative discourse were moderate and weak with estimated intellectual ability. Differences in focal lesion effects after traumatic versus nontraumatic brain injury in children, the contribution of diffuse white matter injury, reduced opportunity for language development, and functional commitment of left frontal region at time of CHI were discussed.

Adolescent↗
PubMed2001

17alpha-methyl testosterone is a competitive inhibitor of aromatase activity in Jar choriocarcinoma cells and macrophage-like THP-1 cells in culture.

17alpha-methyl testosterone is a synthetic androgen with affinity for the androgen receptor. 17alpha-methyl testosterone is used widely as a component of hormone replacement therapy. Previous reports have indicated that contrary to testosterone, 17alpha-methyl testosterone is not aromatized. However, 17alpha-methyl testosterone still could affect local estrogen formation by regulating aromatase expression or by inhibiting aromatase action. Both possibilities have important clinical implications. To evaluate the effect of 17alpha-methyl testosterone on the expression and activity of aromatase, we tested the choriocarcinoma Jar cell line, a cell line that express high levels of P450 aromatase, and the macrophage-like THP-1 cells, which express aromatase only after undergoing differentiation. We found that in both cell lines, 17alpha-methyl testosterone inhibits aromatase activity in a dose-related manner. The curve of inhibition parallels that of letrozole and gives complete inhibition at 10(-4) M 17alpha-methyl testosterone, determined by the tritium release assay. 17alpha-methyl testosterone does not have detectable effects on aromatase RNA and protein expression by Jar cells. Undifferentiated THP-1 cells had no aromatase activity and showed no effect of 17alpha-methyl testosterone, but differentiated THP-1 (macrophage-like) cells had a similar inhibition of aromatase activity by 17alpha-methyl testosterone to that seen in Jar cells. The Lineweaver-Burke plot shows 17alpha-methyl testosterone to be a competitive aromatase inhibitor. Our results show for the first time that 17alpha-methyl testosterone acts as an aromatase inhibitor. These findings are relevant for understanding the effects of 17alpha-methyl testosterone as a component of hormone replacement therapy. 17alpha-methyl testosterone may, as a functional androgen and orally active steroidal inhibitor of endogenous estrogen production, also offer special possibilities for the prevention/treatment of hormone-sensitive cancers.

Aromatase↗
PubMed2001

OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells.

It is important to understand which molecules are essential for long-lived immunity. We show that OX40 (CD134) is required with CD28 for the survival of CD4 T cells following antigen-driven expansion. In contrast to CD28-/- T cells, which show defects early, OX40-/- T cells are relatively unimpaired in IL-2 production, cell division, and expansion. However, OX40-/- T cells fail to maintain high levels of Bcl-xL and Bcl-2 4-8 days after activation, and undergo apoptosis. Conversely, OX40 stimulation promotes Bcl-xL and Bcl-2 and suppresses apoptosis. Moreover, retroviral transduction of OX40-/- T cells with Bcl-xL or Bcl-2 reverses their survival defect. Thus, a temporal relationship exists between CD28 and OX40, with OX40 being a critical regulator of antigen-driven T cell survival.

Animals↗
PubMed2001

The role of the Fas/Fas ligand system in estrogen-induced thymic alteration.

PROBLEM: Estrogen induces atrophy in the thymus by an unknown mechanism. Since the Fas/FasL system is one of the main pathways in T cell apoptosis, we tested the hypothesis that estrogen-induced thymic atrophy is mediated by the Fas/FasL system. METHODS OF STUDY: In vivo experiments were done using ovariectomized female rats treated with estrogen or saline. In vitro experiments were performed using isolated thymocytes. Estrogen receptor (ER) alpha and beta expression was characterized using flow cytometry, RT-PCR and immunofluorescence. Fas and FasL mRNA and protein expression was evaluated using RT-PCR and Western blot analysis respectively. RESULTS: ERalpha and ERbeta are present in thymocytes and stromal cells. ER expression is mainly localized in the Double Positive CD4+CD8+ thymocytes. Estrogen treatment decreases thymus size and increase FasL expression. CONCLUSION: CD4+CD8+ thymocytes and thymic stroma cells express ERalpha and ERbeta. In vivo and in vitro we showed that estrogen treatment increases FasL expression while decreasing thymus cell number. These findings support the hypothesis that estrogen-induced thymic atrophy occurs as a result of apoptosis and is mediated by estrogen-induced FasL expression.

Animals↗