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Biomedical subjects

R Qi

Publications and source records attributed to R Qi.

At least 19 recordsLinked to original sources

Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke.

BACKGROUND: Hyperglycemia at the time of acute ischemic stroke has been linked to worse outcome in both human and animal studies. OBJECTIVE: To describe the prevalence and severity of hyperglycemia on hospital admission among acute ischemic stroke patients, to examine the independent relationship of admission hyperglycemia to all-cause mortality, and to document the inpatient management of hyperglycemia. METHODS: Patients hospitalized with acute ischemic stroke at one hospital from July 1993 to June 1998 (n = 656) were identified. Demographic data, diagnoses, and blood glucose (BG) values were retrieved from the electronic medical record system. Admission stroke severity, fingerstick BG results, and new diabetes diagnoses were obtained by chart review. Hyperglycemia was defined as admitting random serum BG > or = 130 mg/dL. Hazard ratios (HR) for 30-day, 1-year, and 6-year mortality were calculated using multivariable Cox regression models. RESULTS: Hyperglycemia at admission to hospital was present in 40% of patients with acute stroke. Patients with hyperglycemia were more often women and more likely to have prior diagnoses of diabetes and heart failure. Almost all of these patients remained hyperglycemic during their hospital stay (mean BG = 206 mg/dL), and 43% received no inpatient hypoglycemic drugs. Hyperglycemic patients had longer hospital stay (7 vs 6 days, p = 0.015) and higher inpatient hospital charges ($6,611 vs $5,262, p < 0.001). Hyperglycemia independently increased the risk for death at 30 days (HR 1.87, p < or = 0.01), 1 year (HR 1.75, p < or = 0.01), and 6 years after stroke (HR 1.41, p </= 0.01). CONCLUSIONS: Admitting hyperglycemia was common among patients with acute ischemic stroke and was associated with increased short- and long-term mortality and with increased inpatient charges. Inpatient blood glucose management was suboptimal in this hospital. A trial of intensive treatment of hyperglycemia should be considered.

Acute Disease↗

Treatment of antibiotics wastewater utilizing successive hydrolysis, denitrification and nitrification.

A process consisting of anaerobic hydrolysis, denitrification, and oxidation/nitrification was proposed for simultaneous removal of carbon and nitrogen from terramycin crystallizing mother solution (TCMS), and its performance was investigated by treating diluted TCMS in a lab-scale continuous flow column system. Direct denitrification-nitrification of diluted TCMS produced a significant residual of nitrate and nitrite, which disappeared 44 days after startup of anaerobic hydrolysis column. The electron donors available to denitrification were increased by 6 times after diluted TCMS was treated in the hydrolysis column under an HRT of 2.5 h or longer. The reaction rates of organics decomposition, nitrification, and denitrification were also significantly increased due to reduction of terramycin and decomposition of complicated molecules to small molecules during anaerobic hydrolysis. The specific denitrification rate and nitrification rate increased from 0.033 d(-1) and 0.01 d(-1) to 0.045 d(-1) and 0.021 d(-1) respectively after diluted TCMS (dilution ratio: 1:4) was hydrolyzed in anaerobic hydrolysis column at a hydraulic retention time (HRT) of 4 h.

Anti-Bacterial Agents↗

Identification of tumor markers in models of human colorectal cancer using a 19,200-element complementary DNA microarray.

Metastasis represents a crucial transition in disease development and progression and has a profound impact on survival for a wide variety of cancers. Cell line models of metastasis have played an important role in developing our understanding of the metastatic process. We used a 19,200-element human cDNA microarray to profile transcription in three paired cell-line models of colorectal tumor metastasis. By correlating expression patterns across these cell lines, we have identified 176 genes that appear to be differentially expressed (greater than 2-fold) in all highly metastatic cell lines relative to their reference. An analysis of these genes reiterates much of our understanding of the metastatic process and suggests additional genes, many of previously uncharacterized function, that may be causatively involved in, or at least prognostic of, metastasis. Northern analysis of a limited number of these genes validates the observed pattern of expression and suggests that further investigation and functional characterization of the identified genes is warranted.

Biomarkers, Tumor↗

A membrane protein enriched in endoplasmic reticulum exit sites interacts with COPII.

Although all mammalian COPII components have now been cloned, little is known of their interactions with other regulatory proteins involved in exit from the endoplasmic reticulum (ER). We report here that a mammalian protein (Yip1A) that is about 31% identical to S. cerevisiae and which interacts with and modulates COPII-mediated ER-Golgi transport. Yip1A transcripts are ubiquitously expressed. Transcripts of a related mammalian homologue, Yip1B, are found specifically in the heart. Indirect immunofluorescence microscopy revealed that Yip1A is localized to vesicular structures that are concentrated at the perinuclear region. The structures marked by Yip1A co-localized with Sec31A and Sec13, components of the COPII coat protein complex. Immunoelectron microscopy also showed that Yip1A co-localizes with Sec13 at ER exit sites. Overexpression of the hydrophilic N terminus of Yip1A arrests ER-Golgi transport of the vesicular stomatitis G protein and causes fragmentation and dispersion of the Golgi apparatus. A glutathione S-transferase fusion protein with the hydrophilic N terminus of Yip1A (GST-Yip1A) is able to bind to and deplete vital components from rat liver cytosol that is essential for in vitro vesicular stomatitis G transport. Peptide sequence analysis of cytosolic proteins that are specifically bound to GST-Yip1A revealed, among other proteins, mammalian COPII components Sec23 and Sec24. A highly conserved domain at the N terminus of Yip1A is required for Sec23/Sec24 interaction. Our results suggest that Yip1A is involved in the regulation of ER-Golgi traffic at the level of ER exit sites.

Amino Acid Sequence↗

Potentiation of ibudilast inhibition of platelet aggregation in the presence of endothelial cells.

Although communications between platelets and endothelial cells or other blood cells are important in in vivo thrombus formation, laboratory platelet function tests are usually performed in isolation from these surrounding cells. In this study, we evaluated the effect of an antiplatelet drug, ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine), on platelet aggregation in the presence and absence of human umbilical vein endothelial cells (HUVECs) and with the use of platelet-rich plasma (PRP) or whole blood as platelet samples. Stimulation-dependent platelet aggregation was weakened in the presence of HUVECs, which was especially prominent when the thrombin receptor-activating peptide SFLL (compared with ADP and epinephrine) was used as an aggregating agent. Ibudilast hardly affected SFLL-induced platelet aggregation (in PRP), while this antiplatelet agent was found to clearly inhibit this SFLL-induced response in a concentration-dependent manner, in the presence of HUVECs. Ibudilast tended to inhibit ADP- or epinephrine-induced platelet aggregation in the presence of HUVECs, but the effects were not statistically significant. Enhanced inhibition by ibudilast of SFLL-induced platelet aggregation (in the presence of HUVECs) was reproduced with the use of whole blood samples when a screen filtration pressure method was employed. It is suggested that the platelet aggregation studies in the presence of endothelial cells and/or other blood cells provide us with valuable information on platelet reactivity in vivo and improvement of antiplatelet therapy.

Blood Platelets↗

Effects of ischemia on gene expression.

Microarray gene expression technology has recently made it feasible to characterize the RNA expression of thousands of genes across numerous tissue samples. We hypothesized that the warm ischemia commonly associated with the surgical extirpation of human tissue would have significant effects on gene expression profiles. To quantitate the effects of warm ischemia on human tissue, we rapidly dissected normal mucosa from a human colon cancer specimen. The specimen was divided and maintained at room temperature until snap-frozen in liquid nitrogen. Aliquots of tissue were frozen at times 5, 10, 15, 20, 40, and 60 min after extirpation. Spotted microarrays composed of 2400 distinct elements were used to assay mRNA derived from each time point in triplicate. Eisen's hierarchical clustering methodology and Bayesean statistical methods were then used to assay the effects of warm ischemia on gene expression. Application of time-course statistical models suggest that three patterns were induced by ischemia, accounting for 68.2, 17.8, and 13.4% of the evaluable genes, respectively. Pattern I corresponds to an average change of 27% over 60 min from 5 min baseline level of expression and 63.8% of the genes with at least 80% probability of membership in this pattern show average increases in expression over 60 min. The remainder decrease on average. Pattern II genes show the least ischemia-related effects, demonstrating an average change of only 12% over 60 min. In contrast to pattern I, we find that 67.5% of the genes with at least 80% probability of membership in this pattern are decreasing in expression on average over time. The remaining 32.5% in this pattern increase an average of 12% over 60 min. Finally, pattern III genes (13.4% of the sample) show the greatest sensitivity to ischemia, changing an average of 50% over 60 min, with about the same number increasing as are decreasing. Fold changes in RNA over- or under-expression were observed up to greater than 20-fold. Warm ischemia associated with the surgical extirpation of human tissues has significant effects on gene expression. These data support the careful monitoring of ischemic time for tissues harvested for the purpose of gene profiling.

Colonic Neoplasms↗

Shotgun optical maps of the whole Escherichia coli O157:H7 genome.

We have constructed NheI and XhoI optical maps of Escherichia coli O157:H7 solely from genomic DNA molecules to provide a uniquely valuable scaffold for contig closure and sequence validation. E. coli O157:H7 is a common pathogen found in contaminated food and water. Our approach obviated the need for the analysis of clones, PCR products, and hybridizations, because maps were constructed from ensembles of single DNA molecules. Shotgun sequencing of bacterial genomes remains labor-intensive, despite advances in sequencing technology. This is partly due to manual intervention required during the last stages of finishing. The applicability of optical mapping to this problem was enhanced by advances in machine vision techniques that improved mapping throughput and created a path to full automation of mapping. Comparisons were made between maps and sequence data that characterized sequence gaps and guided nascent assemblies.

Contig Mapping↗

Proteins of Mycobacterium bovis BCG induced in the Wayne dormancy model.

Oxygen starvation triggers the shiftdown of the obligate aerobe Mycobacterium bovis BCG to a state of dormancy. Two-dimensional electrophoresis showed a drastic up-regulation of the alpha-crystallin homolog, the putative response regulator Rv3133c, and the two conserved hypothetical proteins Rv2623 and Rv2626c in dormant bacilli.

Aerobiosis↗

Improved O3/H2O2 oxidation process for wastewater reclamation.

A continuous two step O3/H2O2 oxidation system, in which the waste gas from the former reactor was reused in the latter step with an ejector, was established for the purpose of wastewater reclamation in electronics industries. ORP monitor was combined into the system to obtain the optimum ratio of H2O2 to O3 by automatically adjusting the dosage of H2O2, and ion exchange resin was used for removing organic acids formed during oxidation. The effectiveness of the O3/H2O2 oxidation system for TOC removal was investigated under various conditions by using IPA, DMSO, and NMP as model substances. The optimum H2O2/O3 for oxidizing IPA was in a range above 0.15, and it increased with the increase of O3 dose. A sudden drop of ORP from ca. 800 mV to a little more than 200 mV was observed when H2O2/O3 was approaching the optimum point from the lower end. An ORP between 250 mV and 300 mV or 800 mV and 900 mV was proper for H2O2/O3 control. The treatability of the model substances was in an order of IPA << DMSO < NMP, being consistent with the magnitude of the energy of the highest occupied molecular orbital (epsilon HOMO). The two step treatment system developed in this study was found to be more efficient than the conventional single step system. With the help of H2O2 dosing control and two step treatment using waste O3, the system could save about 40% O3 in comparison with the conventional O3/H2O2 oxidation process.

Conservation of Natural Resources↗

The cAMP-mediated protein kinase signal transduction pathway is involved in the pyrogenic effect of CRH in rats.

OBJECTIVE: To determine whether the cyclic adenosine monophosphate (cAMP) mediated protein kinase signal transduction pathway is involved in the pyrogenic action of corticotropin releasing hormone (CRH) in rats. METHODS: Corticotropin releasing hormone, 2',3'-dideoxyadenosine (DDA) and adenosine-3',5'-(cyclic) monophosphorothionate, Rp-Isomer (Rp-cAMPS), were administered intracerebroventricularly (i.c.v.). The colonic temperature was measured using a thermistor, and the content of cAMP in the hypothalamus was determined by radioimmunoassay. Hypothalamic incubation was used to assess the effects of CRH on the content of cAMP in the hypothalamus in vitro. RESULTS: Microinjection (i.c.v.) of CRH (2.5 micrograms, 5.0 micrograms and 10 micrograms) caused increases in colonic temperature and the hypothalamus cAMP level in conscious rats. CRH increased hypothalamus cAMP level in vitro. The pyrogenic effects of CRH were abolished or markedly inhibited by prior injection (i.c.v.) of an adenylate cyclase inhibitor, DDA (30 micrograms), or an inhibitor of cAMP-dependent protein kinase, Rp-cAMPS (15 micrograms). CONCLUSION: cAMP mediates the pyrogenic action of centrally administered of CRH in rats, and protein kinase A may play an important role in the central CRH-induced fever. The cAMP-dependent protein kinase signal transduction pathway may be involved in the central mechanisms of the pyrogenic action of CRH in rats.

Animals↗

[Anaerobic hydrolysis of terramycin crystallizing mother solution].

The terramycin crystallizing mother solution contained high organics and high nitrogen. There were many kinds of bioinhibition in it but not enough electronic donor. Anaerobic hydrolysis of terramycin crystallizing mother solution was completed with up anarobic sludge bed in order to improve the biodegradability of wastewater and electronic donor in it. The variations of pH, COD, NH4+, and SO4(2-) were monitored. The COD removal was in a narrow range between 10% and 16.4% even when the HRT of the reactor was changed from 1.5 h to 6 h. pH increased because of formation of NH3 and reduction of SO4(2-). Most of SO4(2-) was reduced to S2- when the HRT was longer than 2 h. Batch experiments on hydrolyzed wastewater demonstrated that reaction rates of nitrification and denitrification increased by 90.9% and 45.2%, respectively.

Anaerobiosis↗

Inhibition by diallyl trisulfide, a garlic component, of intracellular Ca(2+) mobilization without affecting inositol-1,4, 5-trisphosphate (IP(3)) formation in activated platelets.

Garlic has been used in herbal medicine for thousands of years. Some reports have shown that garlic has protective effects against atherosclerosis and inhibits platelet function. In this study, we investigated the mechanism by which diallyl trisulfide (DT), a component of garlic, inhibits platelet function. DT inhibited platelet aggregation and Ca(2+) mobilization in a concentration-dependent manner without increasing intracellular cyclic AMP and cyclic GMP. DT also had no inhibitory effects on thromboxane A(2) (TXA(2)) production in cell-free systems. Collagen-related peptide (CRP)-induced Ca(2+) mobilization is regulated by phospholipase C-gamma2 (PLC-gamma2) activation. We evaluated the effect of DT on tyrosine phosphorylation of PLC-gamma2 and the production of inositol-1,4,5-trisphosphate (IP(3)). DT at concentrations that inhibited platelet aggregation and Ca(2+) mobilization had no effects on tyrosine phosphorylation of PLC-gamma2 or on the formation of IP(3) induced by CRP. Similar results were obtained with thrombin-induced platelet activation. DT inhibited platelet aggregation and Ca(2+) mobilization induced by thrombin without affecting the production of IP(3.) We then evaluated the effect of DT on the binding of IP(3) to its receptor. DT at high concentrations partially blocked the binding of IP(3) to its receptor. Taken together, our findings suggest that the agent suppresses Ca(2+) mobilization at a step distal to IP(3) formation. DT may provide a good tool for investigating Ca(2+) mobilization.

Allyl Compounds↗

Platelet activation mediated through membrane glycoproteins: involvement of tyrosine kinases.

Fc gamma RII cross-linking and anti-CD9 mAbs included tyrosine phosphorylation of Fc gamma RII, Syk, and Lyn associated with Fc gamma RII in Fc gamma RII cross-linking but not in anti-CD9 mAb-induced platelet activation. We prepared various GST fusion proteins expressing one or two SH2 domains of Syk and evaluated the association between these GST fusion proteins with Fc gamma RII. Based on the results obtained from these experiments, we suggest that only one tyrosine residue in ITAM of Fc gamma RII is phosphorylated with anti-CD9 mAb and that both are phosphorylated with Fc gamma RII cross-linking. Platelet activation mediated by GPIb, the receptor for vWF, is also related with tyrosine phosphorylation. Botrocetin and vWF induced Syk activation. Shc was also rapidly and heavily tyrosine phosphorylated. Sre and Lyn, a 54-kDa tyrosine kinase, was associated with cytoskeletal proteins. When GPIb was immunoprecipitated with nonfunctional anti-GPIb mAbs after platelets were activated with vWF and botrocetin, an in vitro kinase assay revealed the transient association of a kinase activity with GPIb after platelet activation. Phosphoamino acid analysis of phosphorylated proteins in this assay demonstrated that only tyrosine residues but not serine or threonine were phosphorylated, suggesting that the kinase was indeed a tyrosine kinase.

Adaptor Proteins, Signal Transducing↗

Optical mapping of BAC clones from the human Y chromosome DAZ locus.

The accurate mapping of clones derived from genomic regions containing complex arrangements of repeated elements presents special problems for DNA sequencers. Recent advances in the automation of optical mapping have enabled us to map a set of 16 BAC clones derived from the DAZ locus of the human Y chromosome long arm, a locus in which the entire DAZ gene as well as subsections within the gene copies have been duplicated. High-resolution optical mapping employing seven enzymes places these clones into two contigs representing four distinct copies of the DAZ gene and highlights a number of differences between individual copies of DAZ.

Chromosome Mapping↗

A concise guide to cDNA microarray analysis.

Microarray expression analysis has become one of the most widely used functional genomics tools. Efficient application of this technique requires the development of robust and reproducible protocols. We have optimized all aspects of the process, including PCR amplification of target cDNA clones, microarray printing, probe labeling and hybridization, and have developed strategies for data normalization and analysis.

DNA, Complementary↗

Expression of hyaluronan receptors CD44 and RHAMM in stomach cancers: relevance with tumor progression.

Interactions of hyaluronic acid (HA) with its binding proteins CD44 and RHAMM (receptor for HA-mediating motility) have been proposed to be important in promoting tumor progression and dissemination. However, a comparative study of their expression patterns in stomach cancer and its associated lesions is not yet available. To address this issue, the combined examinations of pathology, immunocytochemistry and Western blot hybridization were performed on advanced gastric cancer specimens as well as their preneoplastic and non-cancerous counterparts. Alternative CD44 expression was observed in the gastric mucosa with different lesions. CD44 proteins harboring variant exon 6 (CD44 v6) was detected only in cancer tissues with a total positive rate of 14% (10/74). Intracellular RHAMM molecules in Mr 93000 to 95000 were expressed in 3/31 non-cancerous mucosa. RHAMM detection rates increased along with tumor progression. Irrespective of the differences of gross and morphological pattern, majority (54/74) of cancer cases expressed multiple RHAMM isoforms in Mr 40000-45000, 64000, 70000-73000, 85000 and 93000-95000 with the appearance of cell surface immunocytochemical labeling. Among CD44 variant isoforms, v6 is more relevant with malignant transformation of gastric epithelium. Expression of RHAMM, especially the cell surface variants, is closely correlated with tumor progression (P<0.01). Expression of CD44 and RHAMM may benefit the invasion and metastasis of gastric cancer cells presumably in a reciprocal manner.

Blotting, Western↗