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Biomedical subjects

C Liu

Publications and source records attributed to C Liu.

At least 127 records · Page 7Linked to original sources

Anterior capsular phimosis in eyes with a capsular tension ring.

A 64-year-old woman with zonular weakness in the left eye and a 79-year-old man with bilateral pseudoexfoliation and intraoperative zonular dehiscence had phacoemulsification with in-the-bag implantation of a single-piece poly(methyl methacrylate) intraocular lens (IOL) and a capsular tension ring. Ten to 12 weeks postoperatively, all 3 eyes developed significant visual loss secondary to capsule shrinkage and occlusion of the capsulorhexis opening. All eyes had a neodymium:YAG laser radial anterior capsulotomy, anterior capsulectomy, or both. Visual acuity was restored in all eyes despite slight IOL decentration.

Aged↗

T-Cell recovery in adults and children following umbilical cord blood transplantation.

T-cell reconstitution following allogeneic stem cell transplantation may involve thymic education of donor-derived precursors or peripheral expansion of mature T cells transferred in the graft. T cell-receptor excision circles (sjTRECs) are generated within the thymus and identify new thymic emigrants and those that have not divided. We measured quantitative and qualitative immunologic reconstitution and sjTREC levels in adult and pediatric recipients of umbilical cord blood transplants (UCBTs). sjTRECs were detected at normal levels in all children, starting 12 months after transplantation. sjTRECs were not detected until 18 months after transplantation in adults, and then only at a 3-fold lower level than expected for age. We used complementarity-determining region 3 (CDR3) spectratyping to measure changes in T cell-receptor diversity occurring with restoration of thymic function. T-cell repertoires were skewed in adults and children at 12 to 18 months after transplantation but recovered to near-normal diversity at 2 to 3 years post-UCBT. T-cell repertoires appeared more diverse earlier in children (at 1 to 2 years post-UCBT) than in adults (at 3 to 4 years post-UCBT). We conclude that early T-cell recovery after UCBT occurs primarily through peripheral expansion of adoptively transferred donor T cells and results in skewing of the T-cell repertoire. The reappearance of sjTREC-containing cells after UCBT is associated with increasing numbers of phenotypicaly naive T cells, improved mitogen and recall antigen responses, and diversification of the T-cell repertoire. The delay in central T-cell recovery in adults relative to children may be due to differences in thymic function resulting from age-related atrophy, graft-versus-host disease, or the pharmacologic effects of prophylaxis and treatment of graft-versus-host disease.

Adolescent↗

Translational control is required for the unfolded protein response and in vivo glucose homeostasis.

The accumulation of unfolded protein in the endoplasmic reticulum (ER) attenuates protein synthesis initiation through phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) at Ser51. Subsequently, transcription of genes encoding adaptive functions including the glucose-regulated proteins is induced. We show that eIF2alpha phosphorylation is required for translation attenuation, transcriptional induction, and survival in response to ER stress. Mice with a homozygous mutation at the eIF2alpha phosphorylation site (Ser51Ala) died within 18 hr after birth due to hypoglycemia associated with defective gluconeogenesis. In addition, homozygous mutant embryos and neonates displayed a deficiency in pancreatic beta cells. The results demonstrate that regulation of translation through eIF2alpha phosphorylation is essential for the ER stress response and in vivo glucose homeostasis.

Activating Transcription Factors↗

The surface enhanced Raman scattering effects of composite nanocrystals of Ag-TiO2.

The composite particles of Ag-TiO2 both in a nanocrystal form was prepared by photoreduction of AgNO3 in the rutile colloidal solution. The surface plasmon absorption (SPA) band of the silver clusters supported on the TiO2 nanocrystal was red shift, and a strong surface enhanced Raman scattering (SERS) effect for the composite particles of Ag-nanocrystalline TiO2 was observed. The SERS effect is relating to the red shift phenomenon of SPA band, which could be explained by induced-resonance effect.

Colloids↗

Successful treatment of a large macroprolactinoma with cabergoline during pregnancy.

We report a pregnant woman with a large macroprolactinoma successfully treated with cabergoline after a suboptimal response to bromocriptine. A 7 week pregnant woman with a history of a prolactinoma presented to the endocrine clinic with the complaints of headaches and nausea. She had a prolactin level of 65 microg/L 1 1/2 weeks following her last menstrual period. Bromocriptine was discontinued at 6 weeks gestation when pregnancy was confirmed. A PRL concentration was 1899 microg/L (non-pregnant normal range 1.39-24.20 microg/L, the mean peak levels during pregnancy reported from the literature are 200-210 microg/L) at 7 weeks gestation, and a repeat was 2197 microg/L. An MRI showed a 3 x 2.2 x 2.5 cm seller mass abutting the optic chiasm and displacing the optic nerves superiorly; the visual field testing was normal. Bromocriptine was reinitiated and the patient responded initially with decreasing headaches and declining PRL concentrations to 1488 microg/L at 15 weeks gestation. However, PRL increased to 1836 microg/L at 16 weeks and remained elevated despite bromocriptine 2.5 mg three times a day; in addition, she complained of severe nausea, vomiting, and persistent headaches. Cabergoline was added at 18 weeks gestation. PRL decreased dramatically from 1710 to 859 microg/L in 1 week, and to 488 microg/L within 4 weeks. A repeat MRI showed more than 30% reduction in tumor size. Bromocriptine was discontinued at 24 weeks gestation; she was maintained on cabergoline 0.5 mg twice a week without complaints. PRL levels ranged from 190 to 278 microg/L during the last 10 weeks of pregnancy. She had a C-section electively at 37 weeks gestation and delivered a healthy baby. Management options in this patient and during pregnancy are discussed.

Adult↗

Cognitive correlates of supratentorial atrophy on MRI in multiple sclerosis.

OBJECTIVES: We aimed to investigate associations between neuropsychological indices and normalized volumes of supratentorial structures, and the area of the corpus callosum. MATERIALS AND METHODS: We studied 40 patients with clinically definite MS, using 3D-acquired MRI (MPRAGE, Magnetization Prepared Rapid Acquisition Gradient Echo) and stereology. Subjects underwent a neuropsychological battery interrogating multiple cognitive domains, from which a global Cognitive Index Score (CIS) was derived. RESULTS: White matter volumes were significantly correlated with CIS (rho= -0.59, P<0.0001) and with many of the individual cognitive tests. CIS was also significantly correlated with the corpus callosal area (rho= -0.49, P<0.002). Grey matter volumes did not significantly correlate with any cognitive test. CONCLUSIONS: These volume/function relationships presumably reflect the effects of subcortical axonal and myelin loss on the neural networks that subserve cognition. If serial MRI volume estimations can index accumulating cognitive deficits, this simple technique may be useful in therapeutic trials.

Adult↗

Effects of salviainolic acid A (SA-A) on liver injury: SA-A action on hepatic peroxidation.

BACKGROUND/AIMS: This study aimed to investigate the actions of salviainolic acid A (SA-A), an antiperoxidative component of Salvia miltiorrhiza (Sm), on rat liver injury and fibrosis. METHODS: Acute and chronic rat liver injury models were established using carbon tetrachloride (CCl4). After 48 h (acute) or during 6 weeks of CCl4 injection, rats were further divided and treated with biphenyl dimethyl-dicarboxylate (BDD) or colchicine, as a control antifibrotic treatment, with Sm, a herbal compound, or SA-A, a water-soluble extract of Sm. Liver function was investigated by assessing alanine transaminase (ALT) and aspartate transaminase (AST) activities, histological analysis, hydroxyproline (Hyp) and malondiadehyde (MDA) content. In vitro, isolated cultured hepatocytes were injured with CCl4 gas for 24 h, followed by treatment with either vitamin E or various concentrations of SA-A. The extent of hepatocyte injury was monitored by analyzing various lipid peroxidative parameters such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), lactase dehydrogenase (LDH), and glutathione peroxidase (GSH-PX) levels in hepatocyte supernatants. RESULTS: SA-A significantly decreased abnormal serum ALT activity both in acutely and chronically injured rat livers, decreased abnormal serum AST activity, Hyp and MDA content and attenuated hepatic collagen deposition. After CCl4 incubation and injury, the activities of AST, ALT CAT, GSH-PX and LDH and MDA content in hepatocyte supernatants increased significantly, but GSH levels decreased significantly. SA-A markedly improved these pathological changes in a dose-dependent manner. 10(-4) mol/l SA-A had stronger inhibitory action than vitamin E. CONCLUSIONS: Our studies suggest that SA-A has antiperoxidative effects on injured hepatocytes in liver injury and fibrosis induced by CCl4.

Alanine Transaminase↗

Expression and activity of ADAMTS-5 in synovium.

ADAMTS proteinases, belonging to the adamalysin subfamily of metalloproteinases, have been implicated in a variety of cellular events such as morphogenesis, cell migration, angiogenesis, ovulation and extracellular matrix breakdown. Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) have been identified in cartilage and are largely responsible for cartilage aggrecan breakdown. We have shown previously that synovium, the membrane lining diarthrodial joints, generates soluble aggrecanase activity. We report here the expression, localization and activity of ADAMTS-5 from human arthritic and bovine synovium. ADAMTS-5 was expressed constitutively in synovium with little or no transcriptional regulation by recombinant human interleukin-1 alpha or all-trans-retinoate, factors previously shown to upregulate aggrecanase activity in cartilage. Aggrecanase activity generated by synovium in vitro and recombinant ADAMTS-5 cleaved aggrecan extensively, resulting in aggrecan fragments similar to those generated by chondrocyte-derived aggrecanases, and the activity was inhibited by heparin. ADAMTS-5 was immunolocalized in human arthritic synovium, where staining was mostly pericellular, particularly in the synovial lining and around blood vessels; some matrix staining was also seen. The possibility that synovium-derived ADAMTS-5 may play a role in cartilage aggrecan breakdown is discussed.

ADAM Proteins↗

Ethanol enhances retinoic acid metabolism into polar metabolites in rat liver via induction of cytochrome P4502E1.

BACKGROUND & AIMS: Long-term and excessive ethanol intake results in decreased plasma and hepatic levels of retinoic acid (RA), the most active derivative of vitamin A. The decrease of RA by ethanol treatment has been proposed to be a cytochrome P450 enzyme (CYP)-dependent process. However, the role of the major ethanol-induced CYP, CYP2E1, in the metabolism of RA has not been defined. METHODS: In vitro incubations of RA with microsomal fractions of liver tissue containing CYPs from either ethanol-exposed or non-ethanol-exposed rats were carried out using chemical inhibitors and antibodies against various CYPs. In vivo, both ethanol-exposed and non-ethanol-exposed rats were treated with or without chlormethiazole, a specific CYP2E1 inhibitor, for 1 month. RA and its catabolic metabolites were analyzed by high-performance liquid chromatography and spectral analysis. RESULTS: Incubation of RA with the liver microsomal fraction from ethanol-exposed rats resulted in greater disappearance of RA and increased appearance of 18-hydroxy-RA and 4-oxo-RA compared with control rat liver microsomal fractions. The enhancement of RA catabolism by ethanol was inhibited by both CYP2E1 antibody and specific inhibitors (allyl sulfide and chlormethiazole) in a dose-dependent fashion, whereas the metabolism of RA into polar metabolites was abolished completely by nonspecific CYP inhibitors (disulfiram and liarozole). Furthermore, treatment with chlormethiazole in ethanol-fed rats in vivo restored both hepatic and plasma RA concentrations to normal levels. CONCLUSIONS: Ethanol-induced CYP2E1 plays a major role in the degradation of RA, which may provide a possible biochemical mechanism for chronic and excessive ethanol intake as a risk for both hepatic and extrahepatic cell proliferation and carcinogenesis.

Allyl Compounds↗

Involvement of c-Jun NH2-terminal kinase-1 in heat-induced apoptotic cell death of human monoblastic leukaemia U937 cells.

PURPOSE: To determine the involvement of c-Jun NH(2)-terminal kinase-1 (JNK1) and possibly of HSP27 in heat-induced apoptosis of human monoblastic leukaemia U937 cells. MATERIALS AND METHODS: Dominant negative JNK1 (APF), in which the phosphorylation sites Thr-Pro-Tyr were changed to Ala-Pro-Phe, was overexpressed in U937 cells. Cell viability and DNA fragmentation were analysed by the erythrosin-B dye exclusion test and by agarose gel electrophoresis, respectively. Expression of activated caspase-9, phosphorylated JNK1, JNK2, p38 and HSP27 was examined by Western blotting. JNK1 kinase assay was also performed using c-Jun as a substrate. RESULTS: Loss of viability, activated cleavage form of caspase-9 and DNA fragmentation were rapid in U937 cells after 44 degrees C hyperthermia, while overexpression of dominant negative JNK1 interfered with phosphorylation or activation of JNK1 without affecting that of JNK2 or p38/SAPK, and apparently delayed or reduced cleavage and activation of caspase-9, DNA fragmentation and cell death. Heat-induced phosphorylation of HSP27, observed in parental U937 cells, was suppressed and only slightly detectable in jnk1 mutant cells. CONCLUSIONS: Prolonged phosphorylation or activation of JNK1 was considered important for heat-induced apoptosis and JNK1 may control the process possibly through phosphorylation of HSP27 and caspase-9 activation in U937 cells.

Apoptosis↗

Can asthma education improve clinical outcomes? An evaluation of a pediatric asthma education program.

Asthma is a common, costly, and chronic disease that has a significant impact on children, their families, and the health care system. This study investigated whether formal asthma education can reduce asthma severity and morbidity and further questioned whether the method of education is an important factor in this process. Study subjects were recruited from the emergency department of the Royal Children's Hospital, Melbourne (RCHM), and controls were recruited from the neighboring Western Hospital, Sunshine (WHS). Subject parents were randomized to receive face-to-face education, group education, or home-based video education. Controls had similar medical treatment but received no formal asthma education. Subject and control parents were asked to complete questionnaires before the intervention and at 1, 6, and 12 months. These questionnaires measured demographics, the levels of parent asthma knowledge, anxiety, child asthma severity, and morbidity. Results showed that any method of education increased parent asthma knowledge and immediately decreased their anxiety and child asthma morbidity scores. Despite this, asthma severity was reduced only when knowledge was imparted in an interactive, face-to-face setting. When this happened, asthma severity scores were significantly reduced in both the short- and long-term. These findings call into question mass asthma education campaigns and have important implications for the design of future asthma education programs.

Adult↗

Cationic liposomes enhance cellular/nuclear localization of 99mTc-antisense oligonucleotides in target tumor cells.

UNLABELLED: Efforts are underway to apply strategies developed in connection with antisense chemotherapy to antisense imaging in nuclear medicine. One such strategy is the use of cationic liposome to enhance the cellular uptake of antisense oligonucleotides. METHODS: Using a 99mTc-labeled 18-mer uniformly phosphorothioate DNA antisense to the mRNA of the RI alpha subunit of PKA, the effects of a cationic liposome as carrier on cell uptake and efflux kinetics in tissue culture was evaluated in a RI alpha mRNA positive ACHN cell line. The sense DNA was used as control. RESULTS: Cell uptake was increased 4-5 fold using the liposome carrier compared to the same dosage of naked DNA. Whether naked or liposome-bound, the antisense DNA showed slower efflux from cells compared to the control, resulting in statistically higher accumulation of the antisense compared to the control DNA and suggesting an antisense effect. The internalization and increased cellular accumulation for both antisense and control DNAs with liposomes were demonstrated by microautoradiography and by subcellular fractionation. Finally, using 99mTc-labeled 15-mer antisense DNA against the c-myc oncogene mRNA in MDA-MB-231 cells, significantly more radiolabel was found in total mRNA for the antisense compared to the sense control DNA, both with and without liposome carrier. In conclusion, in tissue culture, the use of a cationic liposome carrier greatly increased cellular uptake and target mRNA binding of 99mTc-labeled antisense DNA.

Autoradiography↗

Restoration of retinoic acid concentration suppresses ethanol-enhanced c-Jun expression and hepatocyte proliferation in rat liver.

Chronic and excessive ethanol intake decreases hepatic retinoic acid (RA) concentrations, which may play a critical role in ethanol-induced hyperproliferation in hepatocytes. The present study was conducted to determine whether RA supplementation in chronic ethanol-fed rats could restore hepatic RA concentrations to normal levels and modulate hepatocyte hyperproliferation. Male Sprague-Dawley rats were divided into four groups: control, ethanol-fed, ethanol-fed + 50 microg all-trans-RA/kg body wt and ethanol-fed + 100 microg all-trans-RA/kg body wt. Ethanol was given to rats at 6.2% (v/v) in a liquid diet to provide 36% of total caloric intake. Control animals received the same amount of liquid diet with isocaloric maltodextrin in place of ethanol. Results show that the ethanol treatment in rats for a month significantly increased the mean number of proliferating cell nuclear antigen (PCNA)-positive hepatocytes [4.96 +/- 1.36% (ethanol-fed) versus 0.29 +/- 0.08% (control), P < 0.05]. This increase was associated with the induction of hepatic c-Jun protein (6.5-fold increase) and cyclin D1 protein (3-fold increase) in ethanol-fed animals as compared with controls. Furthermore, activator protein 1 (AP-1) DNA-binding activity was significantly higher in hepatic nuclear extracts from ethanol-fed rats than those from controls. In contrast, RA supplementation in ethanol-fed rats raised hepatic RA concentration to normal levels and almost completely abolished the ethanol-enhanced c-Jun, cyclin D and AP-1 DNA-binding activities. Moreover, RA supplementation at both doses markedly suppressed the ethanol-induced PCNA-positive hepatocytes by approximately 80%. These results demonstrate that the restoration of hepatic RA concentrations by dietary RA supplementation suppresses ethanol-induced hepatocyte proliferation via inhibiting c-Jun overexpression, and suggest that RA may play a role in preventing or reversing certain types of ethanol-induced liver injury.

Animals↗

Multiple imputation for multivariate data with missing and below-threshold measurements: time-series concentrations of pollutants in the Arctic.

Many chemical and environmental data sets are complicated by the existence of fully missing values or censored values known to lie below detection thresholds. For example, week-long samples of airborne particulate matter were obtained at Alert, NWT, Canada, between 1980 and 1991, where some of the concentrations of 24 particulate constituents were coarsened in the sense of being either fully missing or below detection limits. To facilitate scientific analysis, it is appealing to create complete data by filling in missing values so that standard complete-data methods can be applied. We briefly review commonly used strategies for handling missing values and focus on the multiple-imputation approach, which generally leads to valid inferences when faced with missing data. Three statistical models are developed for multiply imputing the missing values of airborne particulate matter. We expect that these models are useful for creating multiple imputations in a variety of incomplete multivariate time series data sets.

Air Pollutants↗

Anticancer drug-mediated induction of multidrug resistance-associated genes and protein kinase C isozymes in the T-lymphoblastoid cell line CCRF-CEM and in blasts from patients with acute lymphoblastic leukemias.

The major determinants mediating drug resistance in acute lymphoblastic leukemias (ALL) unresponsive to chemotherapy, are still unclear. For example, it is still unknown whether selection or induction processes are responsible for drug resistance here or whether protein kinase C (PKC) isozymes contribute to the resistant phenotype. Therefore, inducibility of resistance factors or PKC isozymes genes was examined in CCRF-CEM cells treated with diverse anticancer drugs--adriamycin, camptothecin, etoposide or vincristine--at sublethal concentrations for 24 h. MDR1, MRP1, LRP and PKC isozyme alpha, beta(1), beta(2), epsilon, iota, eta, theta, zeta gene expression was determined by cDNA-PCR. We found significant dose-dependent, mostly combined, induction of the MDR1, MRP1 and LRP genes. Significantly enhanced gene expression of the majority of PKC isozyme genes was found after treatment with camptothecin. PKCzeta was upregulated throughout by each anticancer drug applied in this setting. A series of selected CCRF-CEM-derived multidrug resistance (MDR) sublines also showed enhanced expression of the PKC isozymes compared to the parental cell line. MDR1 and PKCeta gene expression levels were correlated highly significantly. Blasts from two patients with ALL during the first week of monotherapy with steroids revealed combined induction of the MDR1, multidrug resistance-associated protein 1 (MRP1), lung cancer resistance-related protein (LRP) and most PKC isozymes, predominantly PKCzeta. Another patient with T-ALL, who failed to respond to four months of intensive chemotherapy, showed an enhanced MRP1 gene expression combined with markedly overexpression of PKCeta and PKCtheta. Furthermore, the camptothecin and etoposide-mediated induction of resistance factors in the CCRF-CEM cell line could be suppressed by staurosporine, a rather unspecific inhibitor of protein kinases. However, selective inhibitors of PKC isozymes (bisindolylmaleimide GO 6850, indolocarbazole GO 6976) produced no significant effects here. Therefore, the PKC isozymes eta, theta and zeta are of interest as potential targets to overcome drug resistance in ALL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

AAPM protocol for 40-300 kV x-ray beam dosimetry in radiotherapy and radiobiology.

The American Association of Physicists in Medicine (AAPM) presents a new protocol, developed by the Radiation Therapy Committee Task Group 61, for reference dosimetry of low- and medium-energy x rays for radiotherapy and radiobiology (40 kV < or = tube potential < or = 300 kV). It is based on ionization chambers calibrated in air in terms of air kerma. If the point of interest is at or close to the surface, one unified approach over the entire energy range shall be used to determine absorbed dose to water at the surface of a water phantom based on an in-air measurement (the "in-air" method). If the point of interest is at a depth, an in-water measurement at a depth of 2 cm shall be used for tube potentials > or = 100 kV (the "in-phantom" method). The in-phantom method is not recommended for tube potentials < 100 kV. Guidelines are provided to determine the dose at other points in water and the dose at the surface of other biological materials of interest. The protocol is based on an up-to-date data set of basic dosimetry parameters, which produce consistent dose values for the two methods recommended. Estimates of uncertainties on the final dose values are also presented.

Air↗

A two-microphone dual delay-line approach for extraction of a speech sound in the presence of multiple interferers.

This paper describes algorithms for signal extraction for use as a front-end of telecommunication devices, speech recognition systems, as well as hearing aids that operate in noisy environments. The development was based on some independent, hypothesized theories of the computational mechanics of biological systems in which directional hearing is enabled mainly by binaural processing of interaural directional cues. Our system uses two microphones as input devices and a signal processing method based on the two input channels. The signal processing procedure comprises two major stages: (i) source localization, and (ii) cancellation of noise sources based on knowledge of the locations of all sound sources. The source localization, detailed in our previous paper [Liu et al., J. Acoust. Soc. Am. 108, 1888 (2000)], was based on a well-recognized biological architecture comprising a dual delay-line and a coincidence detection mechanism. This paper focuses on description of the noise cancellation stage. We designed a simple subtraction method which, when strategically employed over the dual delay-line structure in the broadband manner, can effectively cancel multiple interfering sound sources and consequently enhance the desired signal. We obtained an 8-10 dB enhancement for the desired speech in the situations of four talkers in the anechoic acoustic test (or 7-10 dB enhancement in the situations of six talkers in the computer simulation) when all the sounds were equally intense and temporally aligned.

Algorithms↗