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Biomedical subjects

B Han

Publications and source records attributed to B Han.

At least 37 records · Page 2Linked to original sources

Disruption of gamma-glutamyl leukotrienase results in disruption of leukotriene D(4) synthesis in vivo and attenuation of the acute inflammatory response.

To study the function of gamma-glutamyl leukotrienase (GGL), a newly identified member of the gamma-glutamyl transpeptidase (GGT) family, we generated null mutations in GGL (GGL(tm1)) and in both GGL and GGT (GGL(tm1)-GGT(tm1)) by a serial targeting strategy using embryonic stem cells. Mice homozygous for GGL(tm1) show no obvious phenotypic changes. Mice deficient in both GGT and GGL have a phenotype similar to the GGT-deficient mice, but approximately 70% of these mice die before 4 weeks of age, at least 2 months earlier than mice deficient only in GGT. These double-mutant mice are unable to cleave leukotriene C(4) (LTC(4)) to LTD(4), indicating that this conversion is completely dependent on the two enzymes, and in some organs (spleen and uterus) deletion of GGL alone abolished more than 90% of this activity. In an experimental model of peritonitis, GGL alone is responsible for the generation of peritoneal LTD(4). Further, during the development of peritonitis, GGL-deficient mice show an attenuation in neutrophil recruitment but not of plasma protein influx. These findings demonstrate an important role for GGL in the inflammatory response and suggest that LTC(4) and LTD(4) have distinctly different functions in the inflammatory process.

Animals↗

CCK independently activates intracellular trypsinogen and NF-kappaB in rat pancreatic acinar cells.

In the cholecystokinin (CCK) hyperstimulation model of acute pancreatitis, two early intracellular events, activation of trypsinogen and activation of nuclear factor-kappaB (NF-kappaB), are thought to be important in the development of the disease. In this study, the relationship between these two events was investigated. NF-kappaB activity was monitored by using a DNA binding assay and mob-1 chemokine gene expression. Intracellular trypsin activity was measured by using a fluorogenic substrate. Protease inhibitors including FUT-175, Pefabloc, and E-64d prevented CCK stimulation of intracellular trypsinogen and NF-kappaB activation. Likewise, the NF-kappaB inhibitors pyrrolidine dithiocarbamate and N-acetyl-L-cysteine inhibited CCK stimulation of NF-kappaB and intracellular trypsinogen activation. These results suggested a possible codependency of these two events. However, CCK stimulated NF-kappaB activation in Chinese hamster ovary-CCK(A) cells, which do not express trypsinogen, indicating that trypsin is not necessary for CCK activation of NF-kappaB. Furthermore, adenovirus-mediated expression in acinar cells of active p65 subunits to stimulate NF-kappaB, or of inhibitory kappaB-alpha molecules to inhibit NF-kappaB, did not affect either basal or CCK-mediated trypsinogen activation. Thus trypsinogen and NF-kappaB activation are independent events stimulated by CCK.

Acetylcysteine↗

The impact of age, gender, and race on the relationship between depression and self-rated health in community-dwelling older adults: a longitudinal study.

OBJECTIVE: To examine whether the prediction of baseline depression for subsequent changes in self-rated health is consistent across different age cohorts, gender, and racial groups. DATA SOURCES AND STUDY SETTING: A total of 6,714 participants who were 65 years old or older and took part in both the first and the second wave of Assets and Health Dynamics among the Oldest-Old (AHEAD) national survey of community-dwelling older adults were examined. STUDY DESIGN: A two-year prospective cohort study. PRINCIPLE FINDINGS: Baseline depression was an independent risk factor, which not only decreased the odds of having substantial improvement in self-rated health but also increased the possibility of having substantial decline in self-rated health in older men and women, and in Blacks and Whites of all age groups. CONCLUSIONS: Early prevention and treatment of depression among community-dwelling older adults may not only reduce their health decline but also promote their health.

Activities of Daily Living↗

The structure of self-rated health among community-dwelling older adults with stroke.

OBJECTIVE: To examine whether depressive symptomatology is a third fundamental component of the structure of self-rated health, in addition to two other components (physical disease and functional disability) among community-dwelling older adults with stroke. DATA SOURCES AND STUDY SETTING: A total of 591 community-dwelling older adults with stroke were identified from the 1993 Asset and Health Dynamics among the Oldest-Old (AHEAD) national survey of community-dwelling older adults. STUDY DESIGN: A cross-sectional study. Structural equation modeling was applied to compare a widely used two-factor model of self-rated health with a model adding depression as a third possible factor. PRINCIPLE FINDINGS: The hypothesized three-factor model explained additional 21% more variance of self-rated health of older adults with stroke (R2 = 79%, NNFI = 0.95, CFI = 0.96, RMSEA = 0.04) as compared with the two-factor biomedical model (R2 = 58%, NNFI = 0.95, CFI = 0.98, RMSEA = 0.05). The three-factor model was statistically different from the two-factor model. CONCLUSIONS: Greater attention should be given to the theoretical structure of self-rated health of older adults with stroke, particularly, the significant impact of depression on their self-rated health.

Activities of Daily Living↗

Hand-transmitted vibration and biodynamic response of the human hand-arm: a critical review.

Hand-arm vibration syndrome (HAVS) has been associated with prolonged exposure to vibration transmitted to the human hand-arm system from hand-held power tools, vibrating machines, or hand-held vibrating workpieces. The biodynamic response of the human hand and arm to hand transmitted vibration (HTV) forms an essential basis for effective evaluations of exposures, vibration-attenuation mechanisms, and potential injury mechanisms. The biodynamic response to HTV and its relationship to HAVS are critically reviewed and discussed to highlight the advances and the need for further research. In view of its strong dependence on the nature of HTV and the lack of general agreement on the characteristics of HTV, the reported studies are first reviewed to enhance an understanding of HTV and related issues. The characteristics of HTV and relevant unresolved issues are discussed on the basis of measured data, proposed standards, and measurement methods, while the need for further developments in measurement systems is emphasized. The studies on biodynamic response and their findings are grouped into four categories based on the methodology used and the objective. These include studies on (1) through-the-hand-arm response, expressed in terms of vibration transmissibility; (2) to-the-hand response, expressed in terms of the force-motion relationship of the hand-arm system; (3) to-the-hand biodynamic response function, expressed in terms of vibration energy absorption; and (4) computer modeling of the biodynamic response characteristics.

Arm↗

Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats.

Cumulating evidence suggests that enhanced oxidative stress may contribute to diabetic angiopathy. The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-hydroxyguanine (8-OHG), indicators of oxidative DNA damage, in tissue or body fluid are increased in diabetic patients. However, it is unclear whether plasma 8-OHG correlates with tissue 8-OHdG and whether insulin or antioxidant treatment reduces plasma 8-OHG in diabetic state. In this study, we measured the 8-OHG levels in plasma as well as the 8-OHdG levels in liver and kidney in streptozotocin-induced diabetic rats (DR) treated with insulin (DR+I), insulin and probucol (DR+I/P), or insulin and vitamin E (DR+I/E). There was a correlation between plasma 8-OHG levels and tissue 8-OHdG levels (plasma 8-OHG vs. liver 8-OHdG: r = 0.64, P < 0.001; plasma 8-OHG vs. kidney 8-OHdG: r = 0.38, P = 0.06). DR had levels of plasma 8-OHG that were three times higher than control rats (CR), whereas they had levels of tissue 8-OHdG that were approximately 1.5-2 times higher. Plasma 8-OHG levels in DR were almost normalized by insulin treatment, although insulin partially corrected hyperglycemia (plasma 8-OHG: CR 3.3 +/- 2.7 pmol/ml; DR 10.4 +/- 2.3 pmol/ml, P < 0.05 vs. CR; DR with insulin 3.6 +/- 1.0 pmol/ml, P < 0.05 vs. DR). However, tissue 8-OHdG levels in DR were significantly decreased by combined treatment with insulin and antioxidant (probucol or vitamin E), but not by insulin treatment alone. This data suggests that plasma 8-OHG could be a useful biomarker of oxidative DNA damage in diabetic subjects. The mechanism of differential response of plasma 8-OHG and tissue 8-OHdG to insulin and antioxidant treatment remains to be elucidated.

8-Hydroxy-2'-Deoxyguanosine↗

Inhibition of tumor necrosis factor-alpha (TNF-alpha) production and arthritis in the rat by GW3333, a dual inhibitor of TNF-alpha-converting enzyme and matrix metalloproteinases.

Tumor necrosis factor-alpha (TNF)-converting enzyme (TACE) cleaves the precursor form of TNF, allowing the mature form to be secreted into the extracellular space. GW3333, a dual inhibitor of TACE and matrix metalloproteinases (MMPs), was compared with an anti-TNF antibody to evaluate the importance of soluble TNF and MMPs in rat models of arthritis. Oral administration of GW3333 completely blocked increases in plasma TNF after LPS for up to 12 h. In a model wherein intrapleural zymosan injection causes an increase in TNF in the pleural cavity, GW3333 completely inhibited the increase in TNF in the pleural cavity for 12 h. Under these dosing conditions, the plasma levels of unbound GW3333 were at least 50-fold above the IC(50) values for inhibition of individual MMPs in vitro. In a model wherein bacterial peptidoglycan polysaccharide polymers reactivate a local arthritis response in the ankle, a neutralizing anti-TNF antibody completely blocked the ankle swelling over the 3-day reactivation period. GW3333 administered b.i.d. over the same period also inhibited ankle swelling, with the highest dose of 80 mg/kg being slightly less active than the anti-TNF antibody. In a 21-day adjuvant arthritis model, the anti-TNF antibody did not inhibit the ankle swelling or the joint destruction, as assessed by histology or radiology. GW3333, however, showed inhibition of both ankle swelling and joint destruction. In conclusion, GW3333 is the first inhibitor with sufficient duration of action to chronically inhibit TACE and MMPs in the rat. The efficacy of GW3333 suggests that dual inhibitors of TACE and matrix metalloproteinases may prove therapeutic as antiarthritics.

ADAM Proteins↗

[Production of transgenic lamb integrated with modified human anti-trypsin gene].

This experiment is to produce the human mAAT(modified anti-trypsin) which cures the emphysema specifically through mammalian galactophore of transgenic goat. 56 goats were selected as donor for superovulation by FSF + LH microinjection in this experiment. The pronucleic embryos were injected with human mAAT gene after fertilization in vivo, and transferred to the donors or receptors directly. The superovulation was better in March and May than in December with the number of ovulation of 19.50, 21.70 and 16.06, and number of fertilized embryos of 4.31, 6.48 and 3.57 per-animal respectively. The pregnant rates were 18.18% and 25% respectively after transferred to donors and receptors with natural estrus. The donors also can be used as the embryo receptor with no remarkable decrease of pregnant rate. 29 lamb were labored. 4 positive transgenic lamb were checked by PCR, PCR-Southern and Southern analysis. The integrated efficiency of foreign DNA was 13.79% with microinjection of high copy number of foreign DNA fragment.

Animals↗

[Relationship between growth potential of pine, population density of Monochamus alternatus and pathogenicity of Bursaphlenchus xyloophilus].

The results showed that the growth potential of pine (x) is negative related to the population density of Monochamus alternatus (y) and the pathoyenecity of Bursaphlenchus xyloophilus (z). But the population density of Monochamus alternatus is positively related to the pathogenicity of Bursaphlenchus xyloophilus. Three linear equations regression line were established as y = 1793.771 - 16404.47x, z = 31.80989 - 241.9274x, y = -407.611 + 70.51478z. Correlation coefficient is -0.8139, -0.8770 and +0.9864 respectively.

Animals↗

[Construction of a subtracted cDNA library of differentially expressed genes in human normal liver tissue and primary hepatocellular carcinoma tissue].

OBJECTIVE: To construct a subtracted cDNA library of differentially expressed genes in human normal liver tissue and primary hepatocellular carcinoma (HCC) tissue. METHODS: Using the suppression subtractive hybridization (SSH), a novel technique has been described recently. cDNA fragments of missing or low expressing tumor suppressor genes in HCC tissue were isolated using paracancerous normal liver tissue and HCC tissue as targets. Then these cDNA fragments were directly inserted into T/A cloning vector to set up the subtractive library. Amplification of the library was carried out with transformation of E.coli by high voltage electroperforation. One hundred positive bacteria clones were randomly picked and identified using enzyme restriction method. RESULTS: The amplified library contained more than 4,000 positive bacteria clones. Random analysis of 100 clones with enzyme restriction method showed that all clones contained 200-600 bp inserts. CONCLUSIONS: A subtracted cDNA library of differentially expressed genes in human normal liver tissue and HCC tissue is constructed successfully with SSH and T/A cloning techniques. The library is efficient and lays solid foundation for screening and cloning new and specific missing or low expressing tumor suppressor genes of HCC.

Carcinoma, Hepatocellular↗

Effect of CO(2) and CHF(3) on the Solubilization of Protein in Reverse Micelles.

The effect of dissolved CO(2) and CHF(3) on the precipitation of bovine serum albumin (BSA) from reverse micelles of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) in 2,2,4-trimethylpentane (iso-octane) has been studied at 308.15 K. It was found that BSA can be precipitated completely by CO(2) while the AOT and water remain in the iso-octane continuous phase. This opens up a possibility for recovery of protein solids directly from reverse micellar solutions. CHF(3) is also an effective agent for precipitation of BSA in the reverse micelles when the expansion coefficient of CHF(3) exceeds 0.4. However, the condition required for complete removal of the BSA using CHF(3) results in some precipitation of AOT and water from the solution. Copyright 2000 Academic Press.

Journal Article↗

Orchestrated transcription of key pathways in Arabidopsis by the circadian clock.

Like most organisms, plants have endogenous biological clocks that coordinate internal events with the external environment. We used high-density oligonucleotide microarrays to examine gene expression in Arabidopsis and found that 6% of the more than 8000 genes on the array exhibited circadian changes in steady-state messenger RNA levels. Clusters of circadian-regulated genes were found in pathways involved in plant responses to light and other key metabolic pathways. Computational analysis of cycling genes allowed the identification of a highly conserved promoter motif that we found to be required for circadian control of gene expression. Our study presents a comprehensive view of the temporal compartmentalization of physiological pathways by the circadian clock in a eukaryote.

Arabidopsis↗

MRG1 expression in fibroblasts is regulated by Sp1/Sp3 and an Ets transcription factor.

MRG1 (melanocyte-specific gene 1 (MSG1)-related gene), a ubiquitously expressed transcription factor that interacts with p300/CBP, TATA-binding protein and Lhx2, is the founding member of a new family of transcription factors. Initial characterization of this newly discovered transcription factor has underscored its potential involvement in many important cellular processes through transcriptional modulation. We previously demonstrated that MRG1 can be induced by various biological stimuli (Sun, H. B., Zhu, Y. X., Yin, T., Sledge, G., and Yang, Y. C. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 13555-13560). As a first step in understanding its role in different biological processes, we investigated mechanisms that regulate transcription of the mouse MRG1 gene in fibroblasts. Transient transfection of Rat1 fibroblast cells with sequential 5'-deletions of mouse MRG1 promoter-luciferase fusion constructs indicated that the -104 to +121 region contains the full promoter activity. Deletion and site-directed mutations within this region revealed that the Ets-1 site at -97 to -94 and the Sp1 site at -51 to -46 are critical for MRG1 expression in fibroblasts. Gel mobility shift and supershift assays performed with Rat1 nuclear extracts identified nucleoprotein complexes binding to the Ets-1 site and the Sp1 site. In Drosophila SL2 cells, which lack the Sp and Ets family of transcription factors, expression of Sp1, Sp3, and Ets-1 or Elf-1 functionally stimulated MRG1 promoter activity in a synergistic manner. These results suggest that multiple transcription factors acting in synergy are responsible for MRG1 expression and the responsiveness of cells to different biological stimuli.

Animals↗

Lifelong feeding of a high aluminum diet to mice.

In three experiments, high aluminum diets (1000 microg Al/g diet) were fed to mice throughout their life span to determine whether neurodegenerative changes were seen with aging. Brain Al concentrations were slightly lower in Al-treated mice than controls. Generally, no increased mortality or gross evidence of neurodegeneration was seen in Al-treated mice. Eighteen and 24 month old Swiss Webster mice fed the high aluminum diet differed from controls on some neurobehavioral tests, but differences were no greater than previously seen with shorter term exposure in younger mice. Both brain Al concentration and susceptibility to oxidative damage, as measured with TBARS, were lower in the Al-treated aged mice than in controls. In addition, Al-treated aged Swiss Webster and C57BL/6J mice showed somewhat enhanced performance in the Morris water maze. Finally, Al treatment did not exacerbate the effect of MPTP treatment on a grip strength measure in either 66 or 235 day old male mice. Swiss Webster and C57BL/6J mice do not appear to provide useful models for studying Al-induced neurodegenerative changes in aging.

Aluminum↗

Brain-wave representation of words by superposition of a few sine waves.

Data from three previous experiments were analyzed to test the hypothesis that brain waves of spoken or written words can be represented by the superposition of a few sine waves. First, we averaged the data over trials and a set of subjects, and, in one case, over experimental conditions as well. Next we applied a Fourier transform to the averaged data and selected those frequencies with high energy, in no case more than nine in number. The superpositions of these selected sine waves were taken as prototypes. The averaged unfiltered data were the test samples. The prototypes were used to classify the test samples according to a least-squares criterion of fit. The results were seven of seven correct classifications for the first experiment using only three frequencies, six of eight for the second experiment using nine frequencies, and eight of eight for the third experiment using five frequencies.

Acoustic Stimulation↗