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Biomedical subjects

Y Lin

Publications and source records attributed to Y Lin.

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

Chromosomal localization, expression pattern, and promoter analysis of the mouse gene encoding adipocyte-specific secretory protein Acrp30.

Acrp30 is an abundantly expressed secretory protein exclusively synthesized in adipose tissue. Due to the dysregulation in various forms of obesity in humans and mice and its strong structural similarity to TNFalpha, it is currently under study as an important molecule involved in whole body energy homeostasis. Here we describe the sequence of mouse Acrp30 locus, define the intron/exon boundaries and map the gene to the telomere of mouse chromosome 16, syntenic to the human chromosomal locus 3q27. We demonstrate that alternative polyadenylation gives rise to two distinct mRNA species. We also show that Acrp30 expression is induced only at the late stages of mouse embryonic development. Finally, we have characterized the mouse Acrp30 promoter in tissue culture cells. We propose that Acrp30 promoter has the potential to drive strong adipocyte specific heterologous gene expression in transgenic mice.

3T3 Cells↗
PubMed2001

Stabilization and activation of p53 by the coactivator protein TAFII31.

Regulation of the stability of p53 is key to its tumor-suppressing activities. mdm2 directly binds to the amino-terminal region of p53 and targets it for degradation through the ubiquitin-proteasome pathway. The coactivator protein TAF(II)31 binds to p53 at the amino-terminal region that is also required for interaction with mdm2. In this report, we demonstrate that expression of TAF(II)31 inhibits mdm2-mediated ubiquitination of p53 and increases p53 levels. TAF(II)31-mediated p53 stabilization results in activation of p53-mediated transcriptional activity and leads to p53-dependent growth arrest in fibroblasts. UV-induced stabilization of p53 coincides with an increase in p53-associated TAF(II)31 and a corresponding decrease in mdm2-p53 interaction. Non-p53 binding mutant of TAF(II)31 fails to stabilize p53. Our results suggest that direct interaction of TAF(II)31 and p53 not only mediates p53 transcriptional activation but also protects p53 from mdm2-mediated degradation, thereby resulting in activation of p53 functions.

3T3 Cells↗
PubMed2001

Direct interaction between the subunit RAP30 of transcription factor IIF (TFIIF) and RNA polymerase subunit 5, which contributes to the association between TFIIF and RNA polymerase II.

The general transcription factor IIF (TFIIF) assembled in the initiation complex, and RAP30 of TFIIF, have been shown to associate with RNA polymerase II (pol II), although it remains unclear which pol II subunit is responsible for the interaction. We examined whether TFIIF interacts with RNA polymerase II subunit 5 (RPB5), the exposed domain of which binds transcriptional regulatory factors such as hepatitis B virus X protein and a novel regulatory protein, RPB5-mediating protein. The results demonstrated that RPB5 directly binds RAP30 in vitro using purified recombinant proteins and in vivo in COS1 cells transiently expressing recombinant RAP30 and RPB5. The RAP30-binding region was mapped to the central region (amino acids (aa) 47-120) of RPB5, which partly overlaps the hepatitis B virus X protein-binding region. Although the middle part (aa 101-170) and the N-terminus (aa 1-100) of RAP30 independently bound RPB5, the latter was not involved in the RPB5 binding when RAP30 was present in TFIIF complex. Scanning of the middle part of RAP30 by clustered alanine substitutions and then point alanine substitutions pinpointed two residues critical for the RPB5 binding in in vitro and in vivo assays. Wild type but not mutants Y124A and Q131A of RAP30 coexpressed with FLAG-RAP74 efficiently recovered endogenous RPB5 to the FLAG-RAP74-bound anti-FLAG M2 resin. The recovered endogenous RPB5 is assembled in pol II as demonstrated immunologically. Interestingly, coexpression of the central region of RPB5 and wild type RAP30 inhibited recovery of endogenous pol II to the FLAG-RAP74-bound M2 resin, strongly suggesting that the RAP30-binding region of RPB5 inhibited the association of TFIIF and pol II. The exposed domain of RPB5 interacts with RAP30 of TFIIF and is important for the association between pol II and TFIIF.

Animals↗
PubMed2001

Bax accelerates tumorigenesis in p53-deficient mice.

Bax is a Bcl-2 family member that promotes apoptosis and counters the protective effect of Bcl-2. Bax is a downstream effector of p53-induced apoptosis and is transcriptionally regulated by p53. Moreover, the introduction of Bax deficiency accelerates the onset of tumors in transgenic mice expressing truncated large T antigen. These results implicate Bax as a tumor suppressor. Consequently, we asked whether the levels of Bax expression would influence tumor development by comparing Bax-deficient and Bax transgenic mice in the presence or absence of p53. We found that Bax-deficient mice did not display an increased incidence of spontaneous cancers when followed for > 1.5 years. In addition, Bax-deficiency did not further accelerate oncogenesis in mice also deficient in p53. We generated Lck(pr)-Bax transgenic mice to examine the effects of overexpressed BAX on T-cell development and tumorigenesis. Lck(pr)-Bax mice show increased apoptosis consistent with the pro-apoptotic function of Bax. The introduction of p53-deficiency did not interfere with BAX-induced apoptosis; this is consistent with BAX operating downstream or independent of p53. However, we found that Lck(pr)-Bax/p53-deficient mice have an increased incidence of T-cell lymphomas when compared with p53-deficient mice. The Lck(pr)-Bax transgenic mice have an increased percentage of cells in cycle. These findings extend previous work suggesting that Bcl-2 family proteins regulate proliferation as well as cell death. We conclude that BAX-induced proliferation is synergistic with a defect in apoptosis contributed by p53-deficiency. Thus, the dual roles of BAX can either accelerate or inhibit tumorigenesis depending on the genetic context.

Animals↗
PubMed2001

Induction of ureter branching as a response to Wnt-2b signaling during early kidney organogenesis.

Epithelial-mesenchymal tissue interactions play a central role in vertebrate organogenesis, but the molecular mediators and mechanisms of these morphogenetic interactions are still not well characterized. We report here on the expression pattern of Wnt-2b during mouse organogenesis and on tests of its function in epithelial- mesenchymal interactions during kidney development. Wnt-2b is expressed in numerous developing organs in the mouse embryo, including the kidney, lung, salivary gland, gut, pancreas, adrenal gland, and genital tubercle. Additional sites of expression include the branchial arches and craniofacial placodes such as the eye and ear. The data suggest that the expression of Wnt-2b is associated with organs regulated by epithelial-mesenchymal interactions. It is typically localized in the capsular epithelium or peripheral mesenchymal cells of organ rudiments, e.g., the perinephric mesenchymal cells in the region of the presumptive renal stroma in the developing kidney at E11.5. Functional studies of the kidney demonstrate that cells expressing Wnt-2b are not capable of inducing tubule formation but instead stimulate ureter development. Incubation of isolated ureteric buds on such cells supports bud growth and branching. In addition, recombination of Wnt-2b-pretreated ureteric bud tissue with isolated nephrogenic mesenchyme results in a recovery of organogenesis and the expression of epithelial genes within the reconstituted organ explant. Lithium, a known activator of Wnt signaling (Hedgepeth et al. [1997] Dev Biol 185:82-91), is also sufficient to promote ureter branching in the reconstituted kidney in a comparable manner to Wnt-2b signaling, whereas Wnt-4, which induces tubules, neither supports the growth of a ureteric bud nor leads to reconstitution of the ureteric bud with the kidney mesenchyme. We conclude that Wnt-2b may act in the mouse kidney as an early mesenchymal signal controlling morphogenesis of epithelial tissue, and that the Wnt pathway may regulate ureter branching directly. In addition, Wnt signals in the kidney differ qualitatively and are specific to either the epithelial ureteric bud or the kidney mesenchyme.

3T3 Cells↗
PubMed2001

Enhanced apoptosis under low serum conditions in human glioblastoma cells by connexin 43 (Cx43).

Connexin 43 (Cx43), a structural component of gap junctions, is believed to function as a tumor suppressor gene. Previously, we showed that expression of Cx43 suppresses cell proliferation and tumorigenicity of human glioblastoma cells [Huang et al., Cancer Res 58:5089-5096, 1998] and enhances apoptosis in response to chemotherapeutic agents [Huang et al., Int J Cancer 92:130-138, 2001]. In the present study, we demonstrated that expression of Cx43 in human glioblastoma cells potentiated an apoptotic program under low-serum conditions. The Cx43-mediated effect was coupled with a decreased expression of the specific apoptosis-inhibitor bcl-2. Overexpression of bcl-2 in Cx43-transfected cells conferred resistance to apoptosis induced under low-serum conditions, suggesting that the Cx43-mediated apoptosis under low-serum conditions is regulated, in part, through the downregulation of bcl-2 expression. Furthermore, application of the phosphatidylinositol-3'-OH kinase inhibitor LY294002 specifically induced apoptosis in Cx43-transfected cells. Our results demonstrate a new role of Cx43 in the mediation of apoptosis under low serum conditions.

Apoptosis↗
PubMed2001

Organochlorines and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in cancerous and noncancerous breast tissue: do the data support the hypothesis that oxidative DNA damage caused by organochlorines affects breast cancer?

A study was conducted to test the hypothesis that oxidative DNA damage caused by exposure to organochlorines is an important risk factor in breast cancer. This is the first study that evaluates this hypothesis by measuring 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, polychlorinated biphenyl (PCB) congeners, and isomers of bis (4-chlorophenyl)-1,1,1-trichloroethane (DDT) and bis (4-chlorophenyl)-2,2,2-dichloroethane (DDE) in cancerous and noncancerous tissue. We measured these compounds in 44 primary tumors (cancerous) and 21 benign breast biopsy (noncancerous) tissues. Overall, no significant differences were observed in the level of the organochlorines between the tissues. The median concentration for 8-OHdG was 10.5 fmol/mg DNA (1.7/10(5) deoxyguanosine residues), and 8.5 fmol/mg DNA (1.4/10(5) deoxyguanosine residues) in cancerous and noncancerous tissue, respectively. These values are similar to background levels. No significant differences were observed in 8-OHdG levels in cancerous versus noncancerous tissue, and no correlation was demonstrated between the organochlorines and 8-OHdG. The data thus do not support the hypothesis that oxidative DNA damage caused by exposure to organochlorines is an important risk factor in breast cancer.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

Pharmacological evidence for the role of central alpha 1B-adrenoceptors in the motor activity and spontaneous movement of mice.

Central alpha 1-noradrenergic neurotransmission has been shown to be an important complement of dopaminergic transmission in the control of motor activity but the identity of the responsible alpha 1 receptor subtype has not yet been identified. This was investigated in the present experiment by measuring the effects of intraventricular administration of a series of alpha 1 antagonists varying in affinities for the three known receptor subtypes--1a, 1b and 1d--on active behavior in mice in response to a cage change. It was found that the potency of the drugs to block both gross and small movements correlated highly with published affinities for the cloned 1b receptor but not for those of either the cloned 1a or 1d receptors. It is concluded that central alpha 1B receptors are critically involved in the mediation of the (nor)adrenergic influence on active behavior, a finding which has implications for basic and clinical research in both movement and mood disorders.

Adrenergic alpha-Antagonists↗
PubMed2001

Effects of diclofenac in the rat tail ischaemia--reperfusion injury model of acute hyperalgesia.

The rat tail ischaemia--reperfusion model of acute hyperalgesia described by Gelgor et al. (Pain 24 (1986) 251) has been investigated pharmacologically and electrophysiologically. Despite the advantages of this reusable animal model, biochemical changes associated with the behavioural response have not been determined. After injury+/-subcutaneous diclofenac pretreatment, we investigated the behavioural response (changes to thermally-induced tail flick latency) and measured diclofenac, prostaglandin E(2), 6-keto-prostaglandin F(1 alpha) and thromboxane B(2) concentrations in the tail, spinal cord and brain. Subcutaneous injection of 40 mg kg(-1) diclofenac sodium abolished the hyperalgesic response, suppressed the increased eicosanoid production in the tail, inhibited eicosanoid synthesis in the brain, but gave equivocal effects on eicosanoid concentrations in the spinal cord. Injection of 10 and 20 mg kg(-1) diclofenac reduced the duration of hyperalgesia but did not abolish the behavioural response. Diclofenac concentrations in all three tissues were similar, being approximately 5--10% of the corresponding plasma concentrations. We propose that both central and peripheral mechanisms are associated with the hyperalgesia and that the findings lend indirect support to a central action for non-steroidal anti-inflammatory drugs.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Neuronal BC1 RNA: co-expression with growth-associated protein-43 messenger RNA.

Brain-specific cytoplasmic RNA 1 (BC1-RNA), a non-coding RNA polymerase III transcript, is a neuronal RNA that is specifically targeted to dendritic domains. It is co-localized with components of the dendritic protein synthetic machinery, and it has been suggested to operate in the regulation of local translation-related processes in postsynaptic microdomains, thus subserving long-term synaptic plasticity in neurons. To probe the relevance of BC1 expression in neuronal plasticity, we have analyzed the expression pattern of BC1 RNA in the rat nervous system. We found that BC1 RNA is expressed by a specific subset of neurons (but not by non-neuronal cells) in the central and peripheral nervous system of the adult rat. The BC1 labeling pattern indicates that the subcellular location of the RNA is typically postsynaptic which, depending on cell type, manifests itself in a predominantly somatic, somatodendritic, or dendritic location. Our results further show that BC1-expressing neurons typically co-express the messenger RNA for growth-associated protein-43 (GAP-43). Such co-expression was observed in diverse brain areas, including the olfactory bulb, neocortex, and hippocampus, among others. While BC1 RNA was in many neuronal cell types detectable in distal dendritic domains, GAP-43 messenger RNA was typically more restricted to neuronal perikarya. In the mature nervous system, expression of GAP-43 has been described as an intrinsic determinant of predominantly presynaptic plasticity, while BC1 RNA has been implicated in postsynaptic plasticity. Co-expression of both RNAs, as reported here, thus identifies a distinct subset of neurons in the rat nervous system that exhibits both types of plasticity.

Age Factors↗
PubMed2001

Risk for respiratory distress syndrome in preterm infants born to mothers complicated by placenta previa.

This study examined the risk factors for respiratory distress syndrome (RDS) in preterm infants from pregnancies complicated by placenta previa. Forty preterm infants born to mothers with placenta previa between January 1989 and December 1995 in a medical center were enrolled. Each of these patients was matched in gestational age and gender with an infant born immediately after to a mother without placenta previa. Obstetric and neonatal outcome variables were collected. The mean+/-S.D. gestational age for both groups was 33.0+/-3.1 weeks. There was no difference in mean birthweight between the placenta previa and control groups (2129+/-598 vs. 2136+/-493 g). All the patients in the former and 11 (28%) in the latter were born by cesarean section. About a half of the mothers in both groups received antenatal steroids. Infants from placenta previa pregnancies had a higher incidence (21/40 vs. 10/40, P<0.01) and more severe RDS than controls. Stratified by the status of treatment with antenatal steroid, we found that gestational age was a significant risk factor for RDS in both treated and untreated groups (P<0.01), but placenta previa was an independent risk factor (odds ratio 32; CI 1-4182) by multiple exact logistic regression in antenatal steroid-treated group. We conclude that preterm infants born to mothers with placenta previa had a higher risk for RDS than controls. It played an independent role, in addition to gestational age, only in infants treated with antenatal steroid. We speculate that placenta previa was not directly contributing to RDS, but through other associated risk factors for RDS.

Adrenal Cortex Hormones↗
PubMed2001

Expression of Sprouty genes 1, 2 and 4 during mouse organogenesis.

We demonstrate that Sprouty genes 1, 2 and 4 are expressed in several developing organs of the craniofacial area and trunk, including the brain, cochlea, nasal organs, teeth, salivary gland, lungs, digestive tract, kidneys and limb buds. In organs such as the semicircular canal, Rathke's pouch, nasal organs, the follicle of vibrissae and teeth, Sprouty1 and Sprouty2 are expressed in the epithelium and Sprouty4 in the mesenchyme or neuronal tissue, while in the lung Sprouties1, 2 and 4 are all expressed mainly in the epithelial tissue. In the kidney, Sprouty1 is prominent in the ureteric bud whereas Sprouty2 and 4 are expressed in both the ureteric bud and the kidney mesenchyme and glomeruli deriving from it. The expression profiles suggest roles for these Sprouties in the epithelial-mesenchymal interactions that govern organogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Different effects of conjugated linoleic acid isomers on lipoprotein lipase activity in 3T3-L1 adipocytes.

Conjugated linoleic acids (CLAs) are the positional and geometric isomers of linoleic acid. In the present study the effects of cis-9, trans-11 CLA (c9,t11 CLA) and trans-10, cis-12 CLA (t10,c12 CLA ) on intracellular and heparin-releasable (HR-) lipoprotein lipase (LPL) activity in 3T3-L1 adipocytes were investigated. Cells were exposed to the two CLA isomers and linoleic acid, which were bound to bovine serum albumin (BSA). In the adipocytes insulin up-regulated and tumor necrosis factor alpha (TNFalpha) down-regulated HR-LPL activity, which corresponds with the findings in vivo. The experimental fatty acids at low concentrations (<30 µmol/L) moderately increased intracellular and HR-LPL activity. At a concentration of 100 µmol/L, c9,t11 CLA and t10,c12 CLA suppressed HR-LPL activity to 20 and 24% below the BSA control level, respectively, while linoleic acid had no effect unless its concentration was as high as 1000 µmol/L. Insulin abolished the inhibitory effect of c9,t11 CLA, but not of t10,c12 CLA. In the presence of insulin, t10,c12 CLA inhibited HR-LPL activity by 41% compared to BSA control. In contrast to TNFalpha, which suppressed both intracellular LPL and HR-LPL activity, CLAs suppressed HR-LPL activity without decreasing intracellular LPL activity. Additionally, t10,c12 CLA (100 µmol/L) partially prevented TNFalpha-induced decrease of intracellular LPL activity. These results indicate that CLAs differ from linoleic acid in regulating HR-LPL activity, and t10,c12 CLA appeared to be more effective than c9,t11 CLA.

Journal Article↗
PubMed2001

Seasonal allergic rhinoconjunctivitis and fatty acid intake: a cross-sectional study in Japan.

PURPOSE: To investigate the associations of fatty acid intake with seasonal allergic rhinoconjunctivitis. METHODS: The study subjects consisted of 1012 women aged 22 to 57 years (mean age +/- SD: 36.5+/-7.7 years), who had graduated from the Aichi Prefectural Junior College of Nursing, Nagoya, Japan. They completed a self-administered questionnaire on symptoms of the disease in August 1998. Symptoms of seasonal allergic rhinoconjunctivitis in spring were determined by response to the questionnaire, and fatty acid intake was estimated using a food frequency questionnaire. Odds ratios (ORs) were computed using unconditional logistic models to assess the strength of associations between the symptoms and fatty acid intake. RESULTS: An increasing trend in the ORs was observed with increasing dietary intake of n-6 polyunsaturated fatty acids. After adjustment for potential confounders, the ORs for the second, third, and highest quartiles of intake relative to the lowest were 1.28 [95% confidence interval (CI), 0.78-2.10], 1.55 (0.96-2.50), and 1.74 (1.09-2.77), respectively (trend p = 0.015). Consumption of saturated, monounsaturated, and n-3 polyunsaturated fatty acids was not significantly related to the symptoms. CONCLUSIONS: Dietary intake of n-6 polyunsaturated fatty acids was positively associated with seasonal allergic rhinoconjunctivitis in spring.

Adult↗
PubMed2001

Factors affecting phantom scores at annual mammography facility inspections by the U.S. Food and Drug Administration.

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the factors affecting phantom image score at the annual inspection of mammography facilities. MATERIALS AND METHODS: In 1997, three U.S. Food and Drug Administration (FDA)-trained inspectors performed inspections of all mammography facilities in North Carolina. All federal and state inspection data were collected and evaluated by using linear regression analysis. Factors affecting the American College of Radiology phantom scores were assessed. RESULTS: Phantom score was affected by inspector identity, view box luminance, and optical density. All of these factors had a statistically significant effect on mass score (P < .05). Inspector identity yielded a statistically significant effect on speck group score, fibril score, and total score. Luminance yielded a statistically significant effect on both speck group score and total score. CONCLUSION: Phantom scoring should be automated to allow for more consistent interobserver scoring. In addition, radiology facilities can improve the likelihood of receiving a passing phantom score by reducing the ambient light and increasing the view box luminance in the location where the images are evaluated and the phantom is scored routinely. Radiologists should also consider increasing phantom and clinical image optical density to allow for improved phantom testing outcomes.

Breast Diseases↗
PubMed2001

Regulation of PTEN transcription by p53.

PTEN tumor suppressor is frequently mutated in human cancers and is a negative regulator of PI3'K/PKB/Akt-dependent cellular survival. Investigation of the human genomic PTEN locus revealed a p53 binding element directly upstream of the PTEN gene. Deletion and mutation analyses showed that this element is necessary for inducible transactivation of PTEN by p53. A p53-independent element controlling constitutive expression of PTEN was also identified. In contrast to p53 mutant cell lines, induction of p53 in primary and tumor cell lines with wild-type p53 increased PTEN mRNA levels. PTEN was required for p53-mediated apoptosis in immortalized mouse embryonic fibroblasts. Our results reveal a unique role for p53 in regulation of cellular survival and an interesting connection in tumor suppressor signaling.

Animals↗
PubMed2001

Quantitative evaluation of thalami and basal ganglia in infants with periventricular leukomalacia.

Quantitative analyses of cross-sectional areas of the thalami, caudate nuclei, and lentiform nuclei were performed in 29 preterm infants (16 males, 13 females; mean age 29.6 weeks, age range 27 to 24 weeks,) with periventricular leukomalacia (PVL). MRI was carried out in the infants between 9 and 18 months of corrected age and in 16 control infants. Bilateral thalami, caudate nuclei, lentiform nuclei, cerebral hemispheres, and cerebellum were measured by computer. Ratios of the areas of the thalami (Th), caudate nuclei (Ca), lentiform nuclei (Le), and cerebral hemispheres (CH) to that of the cerebellum (Ce) were calculated in each infant. The ratio of Th:Ce was significantly smaller in infants with moderate and severe PVL than in the control group bilaterally. Abnormal intensity areas were not observed in the thalami in any infants with PVL. CH:Ce was also smaller in infants with severe PVL than in the control group. No significant difference was observed between the groups in ratios Le:Ce or Ca:Ce. Results of our study suggest that the volume of the thalami is reduced and that thalamic involvement is present in infants with white matter lesions who have moderate to severe PVL.

Basal Ganglia↗