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Biomedical subjects

R Lin

Publications and source records attributed to R Lin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Infection of central nervous system by motile Enterococcus: first case report.

A 66-year-old man with four indwelling ventriculoperitoneal shunts for multiloculated hydrocephalus from a complicated case of meningitis a year before developed shunt infection based on a syndrome of fever, drowsiness, and cerebrospinal fluid neutrophil pleocytosis in the background of repeated surgical manipulation to relieve successive shunt blockages. The cerebrospinal fluid culture, which yielded a motile Enterococcus species, was believed to originate from the gut. This isolate was lost in storage and could not be characterized further. The patient improved with vancomycin and high-dose ampicillin therapy. He relapsed a month later with Enterococcus gallinarum shunt infection, which responded to high-dose ampicillin and gentamicin therapy. This is probably the first case report of motile Enterococcus infection of the central nervous system.

Aged↗
PubMed2001

Multiple cis regulatory elements control RANTES promoter activity in alveolar epithelial cells infected with respiratory syncytial virus.

Respiratory syncytial virus (RSV) produces intense pulmonary inflammation, in part through its ability to induce chemokine synthesis in infected airway epithelial cells. RANTES (regulated upon activation, normally T-cell expressed and presumably secreted) is a CC chemokine which recruits and activates monocytes, lymphocytes, and eosinophils, all cell types present in the lung inflammatory infiltrate induced by RSV infection. In this study, we analyzed the mechanism of RSV-induced RANTES promoter activation in human type II alveolar epithelial cells (A549 cells). Promoter deletion and mutagenesis experiments indicate that RSV requires the presence of five different cis regulatory elements, located in the promoter fragment spanning from -220 to +55 nucleotides, corresponding to NF-kappaB, C/EBP, Jun/CREB/ATF, and interferon regulatory factor (IRF) binding sites. Although site mutations of the NF-kappaB, C/EBP, and CREB/AP-1 like sites reduce RSV-induced RANTES gene transcription to 50% or less, only mutations affecting IRF binding completely abolish RANTES inducibility. Supershift and microaffinity isolation assays were used to identify the different transcription factor family members whose DNA binding activity was RSV inducible. Expression of dominant negative mutants of these transcription factors further established their central role in virus-induced RANTES promoter activation. Our finding that the presence of multiple cis regulatory elements is required for full activation of the RANTES promoter in RSV-infected alveolar epithelial cells supports the enhanceosome model for RANTES gene transcription, which is absolutely dependent on binding of IRF transcription factors. The identification of regulatory mechanisms of RANTES gene expression is fundamental for rational design of inhibitors of RSV-induced lung inflammation.

CCAAT-Enhancer-Binding Protein-beta↗
PubMed2001

Regulation of gene Expression by 1alpha,25-dihydroxyvitamin D3 and Its analog EB1089 under growth-inhibitory conditions in squamous carcinoma Cells.

Analogs of 1alpha,25-dihydroxyvitamin D(3) (1alpha, 25(OH)2D3) inhibit growth in vitro and in vivo of cells derived from a variety of tumors. Here, we examined the effects of 1alpha,25(OH)2D3 and its analog EB1089 on proliferation and target gene regulation of human head and neck squamous cell carcinoma (SCC) lines SCC4, SCC9, SCC15, and SCC25. A range of sensitivities to 1alpha,25(OH)2D3 and EB1089 was observed, from complete G0/G1 arrest of SCC25 cells to only 50% inhibition of SCC9 cell growth. All lines expressed similar levels of vitamin D3 receptor (VDR) mRNA and protein, and no significant variation was observed in 1alpha,25(OH)2D3-dependent induction of the endogenous 24-hydroxylase gene, or of a transiently transfected 1alpha,25(OH)2D3-sensitive reporter gene. The antiproliferative effects of 1alpha,25(OH)2D3 and EB1089 in SCC25 cells were analyzed by screening more than 4,500 genes on two cDNA microarrays, yielding 38 up-regulated targets, including adhesion molecules, growth factors, kinases, and transcription factors. Genes encoding factors implicated in cell cycle regulation were induced, including the growth arrest and DNA damage gene, gadd45alpha, and the serum- and glucocorticoid-inducible kinase gene, sgk. Induction of GADD45alpha protein in EB1089-treated cells was confirmed by Western blotting. Moreover, while expression of proliferating cell nuclear antigen (PCNA) was reduced in EB1089-treated cells, coimmunoprecipitation studies revealed increased association between GADD45alpha and PCNA in treated cells, consistent with the capacity of GADD45alpha to stimulate DNA repair. While 1alpha,25(OH)2D3 and EB1089 modestly induced transcripts encoding the cyclin-dependent kinase inhibitor p21(waf1/cip1), no changes in protein levels were observed, indicating that p21(waf1/cip1) induction does not contribute to the antiproliferative effects of 1alpha,25(OH)2D3 and EB1089 in SCC cells. Finally, in partially resistant SCC9 cells, there was extensive loss of target gene regulation (10 of 10 genes tested), indicating that resistance arises from widespread loss of 1alpha,25(OH)2D3-dependent gene regulation in the presence of normal levels of functional VDRs.

Blotting, Northern↗
PubMed2001

v-Src-mediated phosphorylation of connexin43 on tyrosine disrupts gap junctional communication in mammalian cells.

It is not clear how the v-Src oncoprotein disrupts gap junctional communication (GJC) established by connexin43 (Cx43) in mammalian cells. In this study, an experimental system was established to stably express v-Src and wild type (wt) Cx43, or Y247F, Y265F, or Y247F/Y265F Cx43 mutants in a Cx43 knockout (KO) mouse cell line. When co-expressed with v-Src, the levels of phosphotyrosine (pTyr) from Y247F, Y265F, and Y247F/Y265F Cx43 mutants were reduced to approximately 57%, 10%, and 2% of the level of pTyr from wt Cx43, indicating that Y247 and Y265 were phosphorylation targets of v-Src in vivo. These data also implied that phosphorylation of Cx43 at Y265 was required for efficient phosphorylation of Cx43 at Y247. Most importantly, our measurements of GJC demonstrated that, in contrast to the wt Cx43 gap junction channels, the Y247F, Y265F, and Y247F/Y265F Cx43 channels were resistant to the disruption by v-Src. In conclusion, our studies support a model for processive phosphorylation of Cx43 on tyrosine, at the Y265 site followed by the Y247 site, in mediating the disruption of GJC induced by v-Src in mammalian cells.

Animals↗
PubMed2001

[Full-scale experiment on corn-ethanol production wastewater treatment with the thermophilic EGSB reactor].

Full-scale EGSB reactor was used in the treatment of corn ethanol production wastewater that was a typical kind of high strength wastewater in North China. As the COD loading rate was as high as 29 kg/(m3.d), the usual SS content was 6000 mg.L-1, COD removal efficiency remained up to 90%, In addition, the reactor started up successfully in only two months with the formation of granular as a symbol. Through this experiment, the conclusion was drawn that the EGSB reactor is greatly efficient in the treatment of corn ethanol production wastewater.

Anaerobiosis↗
PubMed2001

Myocardial protection of immature rabbits with an ATP-sensitive K+ channel opener pinacidil.

OBJECTIVE: To investigate the effectiveness of pinacidil, an opener of ATP-sensitive K+ channels, in protecting the myocardium of immature rabbit hearts from ischemic reperfusion injury. METHODS: Rabbit hearts underwent 30 min of global normothermic ischemia followed by 30 min of reperfusion on the modified Langendorff apparatus. Fifty-two isolated hearts of 3-4 week-old immature rabbits were divided into 4 groups randomly. During ischemia, 3 different cardioplegic solutions were administered intermittently by infusion every 15 min (20-25 ml each time in all groups). Group 1: control group (n = 13); group 2: Krebs-Henseleit (K-H) solution with potassium (16 mmol/L) (n = 13); group 3: K-H solution with potassium (16 mmol/L) and pinacidil (50 mumol/L) (n = 13); group 4: K-H solution with potassium (16 mmol/L), pinacidil (50 mumol/L) and glibenclamide (10 mumol/L) (n = 13). The pre-ischemic and post-ischemic myocardial functions were assessed by the percentage recovery of the left ventricular developed pressure (LVDP); the left ventricular end-diastolic pressure (LVEDP); both the positive peak and negative peaks of the first derivative of the left ventricular pressures (+/- dp/dtmax); coronary flow; the level of creatine kinase (CK), lactic dehydrogenase (LDH) and aspartate transcarbamoylase (AST) in coronary sinus venous effluent; and by myocardial ultrastructural changes. RESULTS: Before myocardial ischemia, there were no significant differences among the four groups in any of the parameters mentioned above. Post-ischemic recovery of LVDP, LVEDP, +/- dp/dtmax, coronary flow, the level of CK, LDH and AST, and myocardial ultrastructural changes were better in group 3 than those in the three other groups. CONCLUSIONS: As a new and effective composition, pinacidil can significantly improve myocardial protection from cardioplegia for immature rabbit hearts.

Animals↗
PubMed2000

Multiple regulatory domains control IRF-7 activity in response to virus infection.

Recent studies implicate the interferon regulatory factors (IRF), IRF-3 and IRF-7, as key activators of Type 1 interferon genes, as well as the RANTES (regulated on activation normal T cell expressed) chemokine gene. Both IRF-3 and IRF-7 are regulated in part by virus-induced C-terminal phosphorylation, leading to nuclear translocation, stimulation of DNA binding, and transcriptional activities. Structure-function studies with IRF-7 suggested a complex organization of the C-terminal region, with a constitutive activation domain located between amino acids 150-246, an accessory inducibility region at the very end of IRF-7 between amino acids 467 and 503, and an inhibitory region (amino acids 341-467) adjacent to the C-terminal end that interferes with transactivation. Furthermore, an element that increases basal and virus-inducible activity is located between amino acids 278 and 305. A transcriptionally active form of IRF-7 was also generated by substitution of Ser-477 and Ser-479 residues with the phosphomimetic Asp. IRF-7, particularly IRF-7(S477D/S479D), was a strong transactivator of type I interferon and RANTES chemokine gene expression. Unlike wild type IRF-3, IRF-7 overexpression was able to stimulate inteferon gene expression in the absence of virus infection. Using tagged versions of IRF-7 and IRF-3, the formation of homo- and heterodimers was detected by co-immunoprecipitation. These results demonstrate that IRF-3 and IRF-7 transcription factors possess distinct structural characteristics that impart complementary rather than redundant functional roles in cytokine gene activation.

Base Sequence↗
PubMed2000

Conformal proton radiation therapy of the posterior fossa: a study comparing protons with three-dimensional planned photons in limiting dose to auditory structures.

PURPOSE: Conventional radiation therapy for pediatric posterior fossa tumors can cause sequelae such as hearing loss and impairments in language and learning. Modern three-dimensional (3D) treatment techniques have improved dose conformity to the posterior fossa. This report compares the normal tissue dose-sparing capabilities of proton radiation therapy (PRT) with 3D conformal photon plans. METHODS AND MATERIALS: Nine children underwent previous PRT for primary CNS malignancies. Using original planning CT scans, the posterior fossa, inner and middle ear, and temporal lobes were delineated. Three-dimensional treatment plans were generated for protons and photons. Normal tissue exposures were calculated by averaging mean doses received and by analysis of dose-volume histogram. RESULTS: The 95% isodose encompassed the posterior fossa in all plans. Normal structures received markedly less radiation from PRT plans than from 3D photon plans. The cochlea received an average mean of 25 +/- 4% of the prescribed dose from PRT, and 75 +/- 6% from photons. Forty percent of temporal lobe volume was completely excluded using protons; with photons 90% of the temporal lobe received 31% of the dose. CONCLUSION: PRT resulted in increased dose sparing of normal structures analyzed. Posterior fossa conformity of 3D photons came at the expense of increasing amounts of normal tissue receiving low to moderate doses.

Child↗
PubMed2000

Activation and regulation of interferon regulatory factor 4 in HTLV type 1-infected T lymphocytes.

The human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL), an aggressive and fatal leukemia of CD4(+) T lymphocytes, and is also associated with a neurological demyelinating disease, tropical spastic paraparesis. The oncogenic potential of HTLV-1 resides in the 353-aa, 40-kDa viral Tax oncoprotein, a positive regulator of viral gene transcription. A novel member of the interferon regulatory factor (IRF) family of transcription factors, IRF-4, was shown to be constitutively produced in HTLV-1-infected cells. IRF-4 is transiently expressed in anti-CD3 and PMA/ionomycin-stimulated T lymphocytes but not in continuous non-Tax-expressing T cell lines. In transient coexpression assays, HTLV-1 Tax protein induced the 1. 2-kb IRF-4 promoter, indicating that Tax functions as an indirect trans-activator of the IRF-4 gene. Furthermore, IRF-4 levels in HTLV-1-infected cells appear to be proportional to the level of Tax expression, suggesting a role for IRF-4 in T cell transformation. In an effort to further characterize IRF-4 function, we identified a novel interaction between IRF-4 and FKBP52, a 59-kDa member of the immunophilin family with peptidyl-prolyl isomerase activity (PPIase). IRF-4-FKBP52 association inhibited the interaction between IRF-4 and its DNA-binding partner PU.1, as well as the trans-activation function of IRF-4/PU.1. FKBP52 association resulted in a structural modification of IRF-4, detectable by immunoblot analysis and by IRF-4 partial proteolysis. These results demonstrate a novel posttranslational mechanism of transcriptional control, mediated through the interaction of an immunophilin with a transcriptional regulator.

Cell Line, Transformed↗
PubMed2000

Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes.

Phosphorylation of histone H3 at serine 10 occurs during mitosis and meiosis in a wide range of eukaryotes and has been shown to be required for proper chromosome transmission in Tetrahymena. Here we report that Ipl1/aurora kinase and its genetically interacting phosphatase, Glc7/PP1, are responsible for the balance of H3 phosphorylation during mitosis in Saccharomyces cerevisiae and Caenorhabditis elegans. In these models, both enzymes are required for H3 phosphorylation and chromosome segregation, although a causal link between the two processes has not been demonstrated. Deregulation of human aurora kinases has been implicated in oncogenesis as a consequence of chromosome missegregation. Our findings reveal an enzyme system that regulates chromosome dynamics and controls histone phosphorylation that is conserved among diverse eukaryotes.

Animals↗
PubMed2000

The gamma-subunit of the coatomer complex binds Cdc42 to mediate transformation.

The Ras-related GTP-binding protein Cdc42 is implicated in a variety of biological activities including the establishment of cell polarity in yeast, the regulation of cell morphology, motility and cell-cycle progression in mammalian cells and the induction of malignant transformation. We identified a Cdc42 mutant (Cdc42F28L) which binds GTP in the absence of a guanine nucleotide exchange factor, but still hydrolyses GTP with a turnover number identical to that for wild-type Cdc42. Expression of this mutant in NIH 3T3 fibroblasts causes cellular transformation, mimicking many of the characteristics of cells transformed by the Dbl oncoprotein, a known guanine nucleotide exchange factor for Cdc42. Here we searched for new Cdc42 targets in an effort to understand how Cdc42 mediates cellular transformation. We identified the gamma-subunit of the coatomer complex (gammaCOP) as a specific binding partner for activated Cdc42. The binding of Cdc42 to gammaCOP is essential for a transforming signal distinct from those elicited by Ras.

3T3 Cells↗
PubMed2000

Phosphorylated syntaxin 1 is localized to discrete domains along a subset of axons.

Syntaxin 1 is a SNARE protein that plays a central role in synaptic vesicle (SV) exocytosis. We generated an antibody that specifically recognizes a casein kinase II-mediated phosphorylation on serine-14 of syntaxin 1. In this report we show that this phosphorylation occurs in vivo and is developmentally regulated in the rat brain, rising to a level of 40% of the total syntaxin in adult animals. Phosphorylated syntaxin is preferentially associated with SNAP-25 and localizes to discrete domains of the axonal plasma membrane that do not colocalize with pools of synaptic vesicles. These phosphosyntaxin domains may define fusion sites for a novel class of vesicles outside classical active zones.

Amino Acid Sequence↗
PubMed2000

Regulation of RANTES chemokine gene expression requires cooperativity between NF-kappa B and IFN-regulatory factor transcription factors.

Virus infection of host cells activates a set of cellular genes, including cytokines, IFNs, and chemokines, involved in antiviral defense and immune activation. Previous studies demonstrated that virus-induced transcriptional activation of a member of the human CC-chemokine RANTES required activation of the latent transcription factors IFN-regulatory factor (IRF)-3 and NF-kappa B via posttranslational phosphorylation. In the present study, we further characterized the regulatory control of RANTES transcription during virus infection using in vivo genomic footprinting analyses. IRF-3, the related IRF-7, and NF-kappa B are identified as important in vivo binding factors required for the cooperative induction of RANTES transcription after virus infection. Using fibroblastic or myeloid cells, we demonstrate that the kinetics and strength of RANTES virus-induced transcription are highly dependent on the preexistence of IRFs and NF-kappa B. Use of dominant negative mutants of either I kappa B-alpha or IRF-3 demonstrate that disruption of either pathway dramatically abolishes the ability of the other to bind and activate RANTES expression. Furthermore, coexpression of IRF-3, IRF-7, and p65/p50 leads to synergistic activation of RANTES promoter transcription. These studies reveal a model of virus-mediated RANTES promoter activation that involves cooperative synergism between IRF-3/IRF-7 and NF-kappa B factors.

Base Sequence↗
PubMed2000

Comparison of a clock drawing test in elderly schizophrenia and Alzheimer's disease patients: a preliminary study.

The objective of this study was to compare between the quantitative and qualitative aspects of a clock drawing test in elderly schizophrenic and Alzheimer's disease (AD) patients. Three independent raters performed a retrospective analysis of the clock drawing item from the Cambridge Cognitive Examination (CAMCOG), in long-term open wards of a public psychiatric hospital and an outpatient psychogeriatric clinic. The study group comprised 21 elderly schizophrenic patients ('graduates') and 21 AD patients matched for gender and education, and cognitive impairment confirmed by a Folstein mini-mental state examination (MMSE) score of 18-23. The Clock Drawing Interpretation Scale (CDIS) was the measure used. Schizophrenic patients were significantly younger than AD patients (63.5 versus 81.3 years, p<0.0001), however, similar concerning gender, education, MMSE and CAMCOG scores. CDIS scores were not correlated with age in eight group. Inter-rater reliability was high (range 0.84-0.97). No significant differences between patient groups were found in mean CDIS total scores. A CDIS specific item analysis revealed that schizophrenic patients were significantly less impaired than AD patients on three out of 20 items: Number 7 (most symbols are aligned in a clockwise or a rightward direction). Number 8 (all symbols are totally within a closure figure), and Number 13 (numbers do not go beyond 12). Although schizophrenic patients and AD patients had similar total scores on the clock drawing test, they differed on specific test items related to spatial/planning deficit and preservation.

Aged↗
PubMed2000

Which patients with hepatitis C develop liver complications?

To identify variables that are independent predictors of adverse outcomes in chronic hepatitis C, we analyzed a cohort of 455 patients followed for a median of 4.7 years. Associations were sought between demographic and behavioral factors, hepatitis C virus (HCV) genotype, liver histology and liver tests at entry, and development of liver complications, hepatocellular carcinoma (HCC), hepatic transplantation and liver-related death. Independent predictors were identified by multivariate analysis. The following were associated with a significantly higher rate of liver complications: age; birth in Asia, Europe, Mediterranean region, or Egypt; transmission by blood transfusion or sporadic cases; HCV genotypes 1b and 4 (compared with 1/1a); fibrosis stage 3 or 4 (cirrhosis); serum albumin; bilirubin; prothrombin time; and alpha-fetoprotein. However, the only independent predictors of liver-related complications were sporadic transmission (P <.001), advanced fibrosis (P =.004), and low albumin (P <.001). The corresponding independent risk factors for HCC were male gender (P =. 07), sporadic transmission (P <.001), and albumin (P <.001); bilirubin (P =.02) was an additional predictor of transplantation or liver-related death. It is concluded that only patients with advanced hepatic fibrosis or cirrhosis, are at risk of developing hepatic complications of chronic hepatitis C during 5-year follow-up. Among such patients, abnormalities in serum albumin, bilirubin, or prothrombin time indicate a high probability of complications. Patients without definite risk factors for HCV (sporadic cases) are at higher risk of complications, possibly because of interaction between older age, duration of infection, country of birth, and HCV genotypes 1b and 4.

Adult↗
PubMed2000

Unusual voltammetry of manganese-substituted myoglobin in surfactant film: evidence for two redox pathways.

The surfactant film methodology is used to examine the electrochemistry of manganese-substituted myoglobin. Cyclic voltammograms at different scan rates depict a dynamic exchange between two redox couples, E1 (-0.25 V vs. SCE) and E2 (-0.41 V). Similar behavior is seen for Mn-substituted cytochrome c peroxidase, but the free cofactor, Mn(protoporphyrin IX) yields a single couple (-0.32 V) under the same conditions. A square scheme is proposed which describes equilibration between two different redox pathways associated with different forms of the protein. Overlapping oxidative currents from these two couples can be deconvoluted, and a pseudo first-order rate constant of 2.3 s(-1) is obtained for the reaction following reduction of Mn(III)Mb. Experiments have been performed to probe possible mechanisms for this equilibrium, such as ligand dissociation or reversible adsorption at the electrode surface. A cofactor-induced reorganization of the protein structure is suggested as the basis of the behavior.

Animals↗
PubMed2000

Posttranslational regulation of IRF-4 activity by the immunophilin FKBP52.

Interferon regulatory factor-4 (IRF-4) plays an important role in immunoregulatory gene expression in B and T lymphocytes and is also highly expressed in human T cell leukemia virus type 1 infected cells. In this study, we characterize a novel interaction between IRF-4 and the FK506-binding protein 52 (FKBP52), a 59 kDa member of the immunophilin family with peptidyl-prolyl isomerase activity (PPIase). IRF-4-FKBP52 association inhibited IRF4-PU.1 binding to the immunoglobulin light chain enhancer E(lambda2-4) as well as IRF-4-PU.1 transactivation, effects that were dependent on functional PPIase activity. FKBP52 association also resulted in a structural modification of IRF-4, detectable by immunoblot analysis and by IRF-4 partial proteolysis. These results demonstrate a novel posttranslational mechanism of transcriptional control, mediated through the interaction of an immunophilin with a transcriptional regulator.

Amino Acid Sequence↗