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Biomedical subjects

Y Chen

Publications and source records attributed to Y Chen.

At least 901 records · Page 50Linked to original sources
PubMed2000

Induction of cell cornification and enhanced squamous-cell marker SPRR1 gene expression by phorbol ester are regulated by different signaling pathways in human conducting airway epithelial cells.

Phorbol ester is a strong inducer for both cell cornification and squamous-cell marker SPRR1 gene expression in conducting airway epithelial cells. However, the signaling pathways involved in the regulation of both events have not been completely elucidated. The current study focuses on the common and divergent pathways involved in the induction of these two activities by phorbol-13-myristate-12-acetate (PMA). Using a protein kinase (PK) C inhibitor, bisindolylmaleimide I, PMA-induced cell cornification and SPRR1 gene expression were abolished. Further, a PKC activator, indolactam V, induced cell cornification in the absence of PMA treatment. These results suggest a PKC-dependent signaling pathway for both gene induction and enhanced cell cornification by PMA. However, a mitogen-activated protein kinase-specific inhibitor, PD98059, could only block the gene induction event but failed to prevent cell cornification induced by PMA. These results suggest that diverse signaling pathways after PKC activation by PMA are involved in the regulation of these two events.

Biomarkers↗
PubMed2000

Time- and dose-related interactions between glucocorticoid and cyclic adenosine 3',5'-monophosphate on CCAAT/enhancer-binding protein-dependent insulin-like growth factor I expression by osteoblasts.

Glucocorticoid has complex effects on osteoblasts. Several of these changes appear to be related to steroid concentration, duration of exposure, or specific effects on growth factor expression or activity within bone. One important bone growth factor, insulin-like growth factor I (IGF-I), is induced in osteoblasts by hormones such as PGE2 that increase intracellular cAMP levels. In this way, PGE2 activates transcription factor CCAAT/enhancer-binding protein-delta (C/EBPdelta) and enhances its binding to a specific control element found in exon 1 in the IGF-I gene. Our current studies show that preexposure to glucocorticoid enhanced C/EBPdelta and C/EBPbeta expression by osteoblasts and thereby potentiated IGF-I gene promoter activation in response to PGE2. Importantly, this directly contrasts with inhibitory effects on IGF-I expression that result from sustained or pharmacologically high levels of glucocorticoid exposure. Consistent with the stimulatory effect of IGF-I on bone protein synthesis, pretreatment with glucocorticoid sensitized osteoblasts to PGE2, and in this context significantly enhanced new collagen and noncollagen protein synthesis. Therefore, pharmacological levels of glucocorticoid may reduce IGF-I expression by osteoblasts and cause osteopenic disease, whereas physiological transient increases in glucocorticoid may permit or amplify the effectiveness of hormones that regulate skeletal tissue integrity. These events appear to converge on the important role of C/EBPdelta and C/EBPbeta on IGF-I expression by osteoblasts.

Animals↗
PubMed2000

Evidence for a functional association between phosphatidylinositol 3-kinase and c-src in the spreading response of osteoclasts to colony-stimulating factor-1.

Osteoclasts are bone-resorbing cells whose normal function depends in part upon their ability to migrate over the bone surface to initiate new sites of bone resorption. The growth factor/cytokine, colony-stimulating factor-1 (CSF-1), potently stimulates osteoclast motility, in a c-src-dependent fashion. The intracellular signaling molecules that participate with c-src in CSF-1-induced remodeling of the osteoclast cytoskeleton have not been identified. Here we demonstrate, using the inhibitors wortmannin and LY294002, that activation of phosphatidylinositol 3-kinase (PI3-K) is required for CSF-1-induced spreading in osteoclasts. After CSF-1 treatment of osteoclast-like cells, PI3-K activity associated with the CSF-1 receptor c-fms, is increased, and the 85-kDa regulatory subunit of PI3-K and c-src coimmunoprecipitate. CSF-1 induces redistribution of PI3-K to the periphery of the cell. The association between p85 and c-src is due in part to a direct interaction between the proline-rich sequences of p85 and the SH3 domain of c-src. In vitro, the c-src SH3 domain stimulates PI3-K activity. Taken together, the current data suggest that c-src, via its SH3 domain, may participate in CSF-1-induced activation of PI3-K and that PI3-K and c-src are in the signaling pathway that subserves CSF-1-induced cytoskeletal changes in osteoclasts.

Androstadienes↗
PubMed2000

Papilin in development; a pericellular protein with a homology to the ADAMTS metalloproteinases.

Papilin is an extracellular matrix glycoprotein that we have found to be involved in, (1) thin matrix layers during gastrulation, (2) matrix associated with wandering, phagocytic hemocytes, (3) basement membranes and (4) space-filling matrix during Drosophila development. Determination of its cDNA sequence led to the identification of Caenorhabditis and mammalian papilins. A distinctly conserved 'papilin cassette' of domains at the amino-end of papilins is also the carboxyl-end of the ADAMTS subgroup of secreted, matrix-associated metalloproteinases; this cassette contains one thrombospondin type 1 (TSR) domain, a specific cysteine-rich domain and several partial TSR domains. In vitro, papilin non-competitively inhibits procollagen N-proteinase, an ADAMTS metalloproteinase. Inhibiting papilin synthesis in Drosophila or Caenorhabditis causes defective cell arrangements and embryonic death. Ectopic expression of papilin in Drosophila causes lethal abnormalities in muscle, Malpighian tubule and trachea formation. We suggest that papilin influences cell rearrangements and may modulate metalloproteinases during organogenesis.

Amino Acid Sequence↗
PubMed2000

Hepatoprotective aliphatic glycosides from three Goodyera species.

Hepatoprotective aliphatic glycosides 3-(S)-3-beta-D-glucopyranosyloxybutanolide (1) and its congener, 3-(S)-3-beta-D-glucopyranosyloxy-4-hydroxybutanoic acid (2) were isolated as major constituents from the whole plants of three Goodyera species, G. schlechtendaliana Reichb. fil., G. matsumurana Schltr. and G. discolor Ker-Gawl. The structures of 1 and 2 have been determined by NMR, MS spectroscopic and chemical means. Compound 1 was converted into its methyl ester form (5) during the purification step, when the lactone ring was cleaved by catalysis of silica gel with the CHCl3-MeOH-H2O as a solvent. On the other hand, 1 was obtained in a high yield by the same purification procedure without MeOH. Based on this fact, a simple and economic method for the purification of 1 was confirmed. Compounds 1 and 2 were found to have a hepatoprotective effect on liver injury induced by carbon tetrachloride in primary cultured rat hepatocytes.

Animals↗
PubMed2000

Regional specialization of ganglion cell layer of the chick retina.

Specialization of the ganglion cell layer (GCL) was studied by Nissl-staining and axonal tract-tracing methods in chicks and chick embryos. The changes in the retinal area and the cell number in the GCL produced a disparity in the cell density that occurred through the two different processes, cell generation (before embryonic days 10-14, E10-14) and cell loss (after E10-14). One high-density area was found in the retinal fundus on E8 (presumptive central area, pCA) and its density decreased toward the peripheral retina. Another high-density area was found in the dorsal retina on E11 (presumptive dorsal area, pDA). Cell densities of the pCA and the pDA on E11 decreased gradually to 25-30% by P1, and after that they further decreased to 40-60% by P30. The pCA was still identified on P30, but the pDA became very obscure by this age. In contrast, ganglion cell sizes increased 5-7 times in the pCA and pDA from E8 to P30, and increased 12 times in the temporal periphery. The present study suggests that the center-peripheral gradient of cell density results from lager scale of cell genesis in the pCA, but not from lager scale of cell loss in the peripheral retina. However, obscuration of the pDA results from equalization of cell density in cellular degeneration processes.

Animals↗
PubMed2000

Effects of aging on bone mineral content and bone biomarkers in female cynomolgus monkeys.

Age-related changes in bone mineral content and bone biomarkers were assessed over the complete lifespan of female cynomolgus monkeys. The bone mass of the lumbar spine increased linearly from birth to about 2.5 years of age, and this increase gradually slowed thereafter until a peak bone mass was achieved at 9 years of age. The bone mass stabilized after 9 years of age, showing no sign of further reduction with age. In contrast with the significant increase in bone mass before 2.5 years of age, significant decreases occurred in the serum concentrations of the following bone formation markers: intact osteocalcin, bone-specific alkaline phosphatase and amino-terminal propeptide of type I procollagen, but the serum concentration of carboxy-terminal propeptide of type I procollagen did not change significantly throughout the entire lifespan. Concerning the bone resorption markers, the levels of tartrate-resistant acid phosphatase fluctuated throughout the entire lifespan. The skeleton of an aging female monkey undergoes changes similar to those observed in senescent humans, but did not undergo the menopausal changes seen in women. The use of female cynomolgus monkeys to model human skeletal interventions should therefore be undertaken with consideration of the similarities and differences between cynomolgus monkeys and humans.

Aging↗
PubMed2000

Role of storage on changes in the mechanical properties of tendon and self-assembled collagen fibers.

Fibrous collagen networks are the major elements that provide mechanical integrity to tissues; they are composed of fiber forming collagens in combination with proteoglycans (PGs). Using uniaxial tensile tests we have studied the viscoelastic mechanical properties of rat tail tendon (RTT) fibers and self-assembled collagen fibers that were stored at 22 degrees C and 1 atm of pressure. Our results indicate that storage of RTT and self-assembled type I collagen fibers results in increased elastic and viscous components of the stress-strain behavior consistent with the hypothesis that storage causes the introduction of crosslinks. Analysis of the elastic and viscous mechanical data suggests that the elastic constant of the collagen molecule in RTT is about 7.7 GPa. Measurement of the viscous component of the stress-strain curves for RTTs and self-assembled collagen fibers suggests that PGs may increase the viscous component and effectively increase the collagen fibril length.

Animals↗
PubMed2000

The role of NF-kappaB in the regulation of the expression of wilms tumor suppressor gene WT1.

The Wilms tumor suppressor gene, WT1, plays an important role in genitourinary development and the etiology of Wilms tumor. WT1 has a spatially and temporally defined expression in the developing genitourinary system and in specific cells of the hematopoietic system, but the regulatory pathways that control WT1 expression are not well understood. Recently, members of the NF-kappaB family of transcription factors have been proposed as potent activators of the murine WT1 promoter through binding to a NF-kappaB site. Because the human WT1 promoter contains a conserved NF-kappaB site, we investigated whether NF-kappaB also regulates the expression of the human WT1 gene. We activated NF-kappaB through cytokine stimulation or inhibited NF-kappaB through expression of a NF-kappaB "super repressor" in WT1 expressing Wilms tumor, renal carcinoma, and erythroleukemia cultures and examined the level of endogenous WT1 gene expression. Although a transfected NF-kappaB reporter construct was responsive to these manipulations, we found that altering NF-kappaB activity had no effect on endogenous WT1 expression in the cell types used in our study. We conclude that despite the presence of conserved NF-kappaB elements in the murine and human WT1 promoters, NF-kappaB is not required to regulate the expression of the WT1 gene in its natural context.

Animals↗
PubMed2000

Inhibition of translation of mRNAs containing gamma-monomethylphosphate cap structure in frog oocytes and in mammalian cells.

The gamma-monomethylphosphate cap structure is found in several eukaryotic small RNAs including nuclear U6, U6atac, 7SK, plant nucleolar U3, and rodent cytoplasmic B2 RNAs. In the case of human U6 snRNA, the 5' end sequence corresponding to nucleotides 1-25 serves as the capping signal and directs the formation of methylphosphate cap structure. In this study, we show that the U6 RNA capping signal, when introduced at the 5' end of RNAs, can efficiently direct the methylphosphate cap formation in RNAs of up to 2.7 kb long, as well as in different mRNAs. These data show that the methylphosphate capping signal functions in mRNAs having different primary sequences and different lengths. Presence of the methylphosphate cap structure on the 5' end of a luciferase mRNA with EMCV 5' noncoding region, which is translated in an IRES-dependent pathway, resulted in a 6- to 100-fold inhibition of translation compared to the same mRNA with a 5' triphosphate when microinjected into frog oocytes or expressed in mouse cells in tissue culture. Thus, conversion of the pppG structure to a methyl-pppG structure on the 5' end of an mRNA, which is translated in an IRES-dependent pathway, results in severe inhibition of translation. These data show that the 5' end motif of mRNAs plays an important role even in the IRES-mediated mRNA translation.

3T3 Cells↗
PubMed2000

MDM2 expression is associated with progress of disease and WAF1 expression in resected lung cancer.

Although MDM2, p21/WAF1, and p53 are considered as regulating each other based on in vitro studies, the relation in human lung cancer is not fully understood. The expressions of these proteins were examined immunohistochemically in 112 resected non-small cell lung cancer specimens and the correlation between them were analyzed. MDM2 was expressed in 45% of all lung cancers. In advanced stage, MDM2-positive cases were observed more frequently than in early stage, showing significant difference. No significant difference was observed in the prognosis of the patients regardless of the expression of any protein. Although no correlation was observed between MDM2 expression and p53 expression, or between p21/WAF1 expression and p53 expression, MDM2 expression was strongly related with p21/WAF1 expression. Therefore, MDM2 expression may relate to the progress of the stage of lung cancer, and MDM2 expression and p21/WAF1 expression may be associated not through the p53-related pathway.

Adenocarcinoma↗
PubMed2000

Modeling the germination kinetics of clostridium botulinum 56A spores as affected by temperature, pH, and sodium chloride.

The germination kinetics of proteolytic Clostridium botulinum 56A spores were modeled as a function of temperature (15, 22, 30 degrees C), pH (5.5, 6.0, 6.5), and sodium chloride (0.5, 2.0, 4.0%). Germination in brain heart infusion (BHI) broth was followed with phase-contrast microscopy. Data collected were used to develop the mathematical models. The germination kinetics expressed as cumulated fraction of germinated spores over time at each environmental condition were best described by an exponential distribution. Quadratic polynomial models were developed by regression analysis to describe the exponential parameter (time to 63% germination) (r2 = 0.982) and the germination extent (r2 = 0.867) as a function of temperature, pH, and sodium chloride. Validation experiments in BHI broth (pH: 5.75, 6.25; NaCl: 1.0, 3.0%; temperature: 18, 26 degrees C) confirmed that the model's predictions were within an acceptable range compared to the experimental results and were fail-safe in most cases.

Animals↗
PubMed2000

[Molecular cytogenetics study in a case with unbalanced chromosome translocation].

OBJECTIVE: To analyze the chromosome structural aberration in a case of unbalanced chromosome translocation by fluorescence in situ hybridization technique. METHODS: The 1,18 whole chromosome specific painting probe were used to confirm chromosome abnormality suggested by high resolution G-banding examination. RESULTS: An unbalanced translocation t(1;18)(q42;q22) was detected in the patient, which caused partial trisomy of 1q42-qter and partial monosomy of 18q22-qter. CONCLUSION: The identified translocation suggested a potential site for congenital heart disease.

Heart Defects, Congenital↗
PubMed2000

[Study of HBV X protein and RMP, an RPB5 mediate protein competitively interacting with general transcription factor TF2B].

OBJECTIVE: HBX is an essential viral protein that is important for HBV replication and might be a cofactor in the development of hepatocellular carcinoma. So many researchers are trying to find out the antagonistic factors of HBX. RMP, a newly cloned RNA polymerase II subunit RPB5 mediate protein, represses the transcription transactivation of HBV X protein. The purpose of this study was to elucidate the mechanism how RMP represses the transactivation of HBX. METHODS: In this report, DNA recombinant technique in vitro protein-protein binding assay (Pull-Down assay) and chloramphenicol acetyltransferase assay were used. RESULTS: The d10 domain of TF2B are responsible for binding to RMP, which is same as TF2B binding to the HBX protein. RMP specifically disrupts the binding between TF2B and HBX protein, vice versa HBX protein also disrupt the interaction of TF2B-RMP as demonstrated by the in vitro protein binding competition assay. Overexpression of RMP represses HBX transactivation on the reporters with HBX responsive cis-elements in transient transfected COS-1 cells. The repression can be rescued by overexpression of TF2B. CONCLUSION: The results clearly suggested that transcription co-activator HBX protein and corepressor RMP competitively associated with TF2B. Disrupting the interaction between transcription co-repressor RMP with TF2B is probably one of the mechanisms to account for the transcriptional transactivation of HBX protein.

Binding, Competitive↗
PubMed2000

Evaluation of renal function in normal and hydronephrotic kidneys in rats using gadolinium diethylenetetramine-pentaacetic acid enhanced dynamic magnetic resonance imaging.

PURPOSE: Magnetic resonance imaging (MRI) is becoming established as a modality complementary to computerized tomography and ultrasound for evaluating kidney function. The evaluation of renal function during ureteral obstruction may be improved by contrast enhanced MRI. We evaluated dynamic changes in relative signal intensity in normal and hydronephrotic rat kidneys after intravenous injection of gadolinium (Gd) diethylenetetramine-pentaacetic acid (DTPA). MATERIALS AND METHODS: Using Gd-DTPA enhanced dynamic MRI we evaluated 35, 1-year-old rats, including 10 with partial and complete unilateral ureteral obstruction, respectively, and 15 with sham operated nonobstructed kidneys. Partial obstruction was created in 2-day-old rats by embedding the left ureter into the psoas muscle. Complete obstruction was created 10 days before MRI by placing a ligature around the upper third of the left ureter. MRI was performed before and 0.1 to 60 minutes after and intravenous injection of Gd-DTPA. We calculated relative signal intensity per time interval in the renal cortex, medulla and pelvis. RESULTS: Dynamic relative signal intensity patterns differed significantly among normal, and partially and completely obstructed kidneys. In normal kidneys signal intensity changes were divided into 3 phases after Gd-DTPA administration. During phase 1 rapid parenchymal uptake of Gd-DTPA within the initial minute after injection produced a rapid signal intensity decrease in the cortex, which achieved a minimum of 28% of pre-injection intensity. During phase 2 signal intensity decreased in the medulla and pelvis to a minimum of 18% and 22%, respectively, of pre-injection intensity within 5 minutes. During phase 3 significant relative signal intensity recovery began in the cortex at 7 minutes, and in the medulla and pelvis at 10 to 15 minutes, and lasted 30 to 60 minutes. In partially obstructed kidneys the 3 phases were significantly slower than in controls. In completely obstructed kidneys only phase 1 occurred within 60 minutes. CONCLUSIONS: Gd-DTPA enhanced dynamic MRI provides useful information for distinguishing obstructed from nonobstructed and partially from completely obstructed kidneys.

Animals↗
PubMed2000

Cannabinoids protect cells from oxidative cell death: a receptor-independent mechanism.

Serum is required for the survival and growth of most animal cells. In serum-free medium, B lymphoblastoid cells and fibroblasts die after 2 days. We report that submicromolar concentrations of Delta(9)-tetrahydrocannabinol (THC), Delta(8)-THC, cannabinol, or cannabidiol, but not WIN 55,212-2, prevented serum-deprived cell death. Delta(9)-THC also synergized with platelet-derived growth factor in activating resting NIH 3T3 fibroblasts. The cannabinoids' growth supportive effect did not correlate with their ability to bind to known cannabinoid receptors and showed no stereoselectivity, suggesting a nonreceptor-mediated pathway. Direct measurement of oxidative stress revealed that cannabinoids prevented serum-deprived cell death by antioxidation. The antioxidative property of cannabinoids was confirmed by their ability to antagonize oxidative stress and consequent cell death induced by the retinoid anhydroretinol. Therefore, cannabinoids act as antioxidants to modulate cell survival and growth of B lymphocytes and fibroblasts.

Antioxidants↗
PubMed2000

Neonatal intussusception due to a cecal duplication cyst.

Intussusception in the first month of life is rare; however, it should be considered a distinct clinical and pathologic entity. Cecal duplication as the cause of intussusception in a neonate is extremely rare. We report a case of a newborn with ileocecocolic intussusception. She presented with vomiting and bloody stools. Abdominal sonography revealed a target lesion with a cystic component. We performed a laparotomy and found an ileocecocolic-type intussusception which was caused by a cecal duplication cyst. Right hemicolectomy with ileocolostomy was performed. She remained well at one year follow-up.

Cecal Diseases↗