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L Liu

Publications and source records attributed to L Liu.

At least 991 records · Page 55Linked to original sources
PubMed1995

Binocular combination of contrast signals from orthogonal orientation channels.

In a series of psychophysical experiments, observers compared the apparent contrast of a dichoptic stimulus (contrast edges of orthogonal orientations in the two eyes) and a monocular stimulus ( a pie pattern in one eye and a blank field in the other eye). When the contrast of the dichoptic stimulus was low (2-3%) the two orthogonal edges were perceived as a stable pie pattern and its apparent contrast matched with that of a monocular pie pattern whose contrast was twice the contrast of the dichoptic stimulus. The dichoptic contrast gain (monocular/dichoptic contrast ratio) decreased with increasing dichoptic contrast. Although the observers showed an inability to discriminate the apparent contrasts of the dichoptic and the monocular pie patterns, they were able to tell which stimulus was the dichoptic one in a forced choice paradigm. A binocular contrast preservation model was proposed for binocular combination of contrast signals from orthogonal orientation channels.

Contrast Sensitivity↗
PubMed1995

Inhibition of secretion from isolated rat alveolar epithelial type II cells by the cell permeant calpain inhibitor II (N-acetyl-leucyl-leucyl-methioninal).

Although several signal transduction pathways, including activation of specific protein kinases have been proposed and studied for the secretory processes of lung surfactant from alveolar epithelial type II cells, the role of proteolytic processing by calpains (calcium-activated neutral proteases) in secretion has not been investigated. Therefore, we examined the effect of cell permeable calpain inhibitor I (N-acetyl-leucyl-leucyl-norleucinal) and II (N-acetyl-leucyl-leucyl-methioninal) on secretion to test the hypothesis that calpains participate in the secretory processes of alveolar epithelial type II cells. Calpain inhibitor I preferentially inhibits micro (mu)-calpain while inhibitor II inhibits milli (m)-calpain. Isolated type II cells were prelabelled with [3H]-choline for 18-24 h. To measure secretion, [3H]-labelled disaturated phosphatidylcholine (DSPC) released in the medium was monitored. Basal secretion of DSPC was maximally (87%) depressed by the presence of 10 microM inhibitor II. Secretagogue-stimulated secretion was also modulated by inhibitor II treatment. Stimulation with calcium ionophore A23187 enhanced secretion 3-fold. However, cells pre-exposed to inhibitor II displayed a 90% reduction of calcium-stimulated secretion. Terbutaline (10 microM) and ATP (1 mM) each increased secretion 2- and 4-fold, respectively. However, the inhibitor-treated cells, exposed to the same stimuli, attained only 53 or 62% of these increases. Calpain inhibitor I, on the other hand, inhibited neither basal nor stimulated secretion. The results suggest that m-calpain, the major isozyme of lung calpain requiring mM calcium for activity in vitro, is involved in the secretory pathways of alveolar epithelial type II cells.

Amino Acid Sequence↗
PubMed1995

Human estrogen receptor messenger RNA variants in both normal and tumor breast tissues.

By using the PCR-SSCP technique we characterized various ER-specific RNA species present in a series of primary breast cancers, as well as in cell lines established from breast carcinomas and in mammary gland tissues from healthy specimens. A series of six truncated messenger RNAs generated by alternative splicing was characterized. These RNAs correspond to specific deletions of one (exons 2-7, except exon 6) or two (exons 3 + 4) exons. All these RNA variants are observed in each one of the analyzed RNAs, regardless of origin. In addition, the relative amount of these different variants in ER + tumors is comparable to that measured in ER - tumors and healthy mammary gland tissues. This data suggests that tumor progression is not related to the emergence of any of the ER mRNA variants.

Alternative Splicing↗
PubMed1995

Insulin elevates hippocampal GABA levels during ischemia. This is independent of its hypoglycemic effect.

There are reports that insulin may protect neurons from the effects of ischemia. The mechanisms for this protection are not fully understood. We studied the extracellular levels of glutamate and GABA in insulin-treated animals exposed to transient forebrain ischemia under normoglycemic and hypoglycemic conditions. In vivo microdialysis technique was used to collect extracellular fluid from the CA1 region of the hippocampus. There was a significant increase in GABA levels in the two insulin-treated sub-groups compared with the controls. GABA levels were < 1 pmol/10 microliters in three 10 min collections prior to ischemia in all the groups. It increased from 11.1 +/- 3.5 pmol/10 microliters in the conrol group to 47 +/- 5 (P < 0.001) in the insulin-treated hypoglycemic group and up to 47.2 +/- 9.3+ (P < 0.005) in the insulin-treated normoglycemic group (two-way ANOVA with repeated measures). Ischemia resulted in an increase in the glutamate levels. The glutamate levels returned to baseline within 30 min of the insult. There were no significant differences in the glutamate levels in three groups. The increase in GABA concentrations in the extracellular space may result in the inhibition of CA1 pyramidal neurons. This may be a possible mechanism of neuronal protection in animals treated with insulin (with or without being hypoglycemic) during ischemia.

Animals↗
PubMed1995

Complement and clusterin in the spinal cord dorsal horn and gracile nucleus following sciatic nerve injury in the adult rat.

We provide evidence for activation of the complement cascade in the dorsal horn of the spinal cord and in the gracile nucleus in the brainstem following sciatic nerve transection in the adult rat. Immunocytochemical analyses showed immunoreactivity for endogenous immunoglobulin G as shown by immunostaining with F(ab')2 antibodies, as well as complement factors C1, C1q, C3, C3d and C9 in the appropriate central termination areas of the injured sciatic nerve. Results from double labelling immunocytochemistry showed a strong association between immunoglobulin and complement factors on the one hand and reactive microglia on the other. However, some complement immunoreactivity was also found in the neuropil, possibly representing secreted complement. In situ hybridization with an oligonucleotide probe showed a marked increase in C3 messenger RNA, indicating local synthesis of C3 protein. In parallel with activation of complement, there was an increased immunoreactivity for the putative complement inhibitor clusterin, which co-localized with glial fibrillary acidic protein-positive astrocytes. In situ hybridization showed an increased labelling of clusterin messenger RNA. These findings indicate that complement activation and up-regulation of complement inhibitors are prominent central responses to peripheral sensory nerve injury. These responses may therefore be important elements underlying so-called transganglionic degenerative changes in primary sensory axons and terminals.

Animals↗
PubMed1995

Control of enantiomer migration order in capillary electrophoresis separations using sulfobutyl ether beta-cyclodextrin.

The control of enantiomer migration order in capillary electrophoresis (CE) by use of sulfobutyl ether beta-cyclodextrin (SBE-beta-CD) was investigated. At high pH, electroosmotic flow (EOF) dominated and the enantiomer most strongly associated with the anionic cyclodextrin was detected last. At low pH (and reversed polarity), EOF was minimal and SBE-beta-CD functioned as a carrier. Under such conditions, the enantiomer migration order for a neutral chiral compound was reversed. Factors involved in optimization (cyclodextrin and organic modifier concentration) were studied. The impact of migration order on quantitation of low levels (below 1%) of one enantiomer in the presence of the other was also investigated. The precision of peak area ratios (minor/major enantiomer) was evaluated for samples of both enantiomers run by each method. The migration of minor before major enantiomer yielded better quantitation precision in each case.

Borates↗
PubMed1995

Elevated extracellular glutamate levels increased the formation of hydroxyl radical in the striatum of anesthetized rat.

Results from various in vitro experiments have indicated that excitotoxicity and oxidative stress are two interrelated major mechanisms in causing neuronal damage in brain disorders such as cerebral ischemia/reperfusion. Thus, we have conducted experiments to investigate whether in the striatum of anesthetized rats the elevated brain extracellular concentrations of glutamate could increase the formation of hydroxyl radical. Elevation of glutamate levels and trapping of hydroxyl radical were accomplished by perfusing Ringer solutions containing both glutamate and salicylic acid through microdialysis probes implanted in rat striatum. The formation of hydroxyl radical was quantitated as the increased amounts of 2,3 and 2,5 dihydroxybenzoic acid (DHBA) which were the hydroxylative products of salicylic acid. Eluted microdialysates were directly injected onto high performance liquid chromatography (HPLC) with electrochemical detector via an on-line automatic injector. This method was authenticated by in vitro studies employing Fenton-type hydroxyl radicals generation system. Our results indicated that elevated glutamate concentrations (15 mM, 1.5 mM, and 150 microM glutamate in perfusing solutions) would significantly increased both the concentrations of 2,3 and 2,5 DHBA. In conclusion, we have obtained direct evidence showing that the elevated glutamate concentrations in brain extracellular space would increase the formation of hydroxyl radical, and these results implied that oxidative stress occurring in brain disorders might be induced by excitotoxicity.

Anesthesia↗
PubMed1995

DNA oxidation as a potential molecular mechanism mediating drug-induced birth defects: phenytoin and structurally related teratogens initiate the formation of 8-hydroxy-2'-deoxyguanosine in vitro and in vivo in murine maternal hepatic and embryonic tissues.

A considerable number of teratogens, including the anticonvulsant drug phenytoin and structurally related drugs and environmental chemicals, may be bioactivated by peroxidases, such as prostaglandin H synthase (PHS) and lipoxygenases (LPOs), to a reactive free radical intermediate that initiates birth defects. However, the molecular targets of the reactive free radical intermediates mediating chemical teratogenesis, and hence the fundamental determinants of susceptibility, are poorly understood. In these studies, a teratogenic dose of phenytoin (65 mg/kg), when injected into pregnant CD-1 mice during organogenesis on gestational day 12, initiated the oxidation of DNA in maternal hepatic and embryonic nuclei, forming 8-hydroxy-2'-deoxyguanosine. Significant maternal and embryonic DNA oxidation occurred at 6 and 3 h, respectively, suggesting relative embryonic deficiencies in free radical-related cytoprotective enzymes, although the rates appeared similar. Maximal DNA oxidation in both maternal and embryonic tissues occurred at 6 h, presumably reflecting the balance of DNA oxidation and repair, the latter of which appeared similar in both tissues. Inhibition of phenytoin-initiated embryonic DNA oxidation by the free radical spin trapping agent alpha-phenyl-N-t-butylnitrone (41.5 mg/kg), and by acetylsalicylic acid (10 mg/kg), an inhibitor of the cyclooxygenase component of PHS, was consistent with the previously reported reduction by these inhibitors of phenytoin-initiated murine birth defects. In vitro studies using a horseradish peroxidase (0.5 mg/ml)-H2O2 (5.45 micrograms/ml) bioactivating system for drug-initiated oxidation of 2'-deoxyguanosine (3.74 mM), indicated that the potency of xenobiotic-initiated formation of 8-hydroxy-2'-deoxyguanosine for the structurally related drugs and metabolites phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, trimethadione, dimethadione, l-mephenytoin, l-nirvanol, d-nirvanol (80 microM each), or thalidomide (64 microM), reflected their murine teratogenic potency. Given the relatively low activities of cytochromes P450, compared to PHS and LPOs, in human and rodent embryonic tissues, these data support the potential teratological importance of peroxidase-catalysed bioactivation of xenobiotics with structural similarities to phenytoin. These studies provide the first evidence that peroxidase-catalysed embryonic DNA oxidation may constitute a critical molecular mechanism mediating the teratogenicity of phenytoin and related drugs and environmental chemicals, and suggest the potential teratological importance of additional embryonic processes, such as DNA repair and tumor suppressor genes, as determinants of susceptibility.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Mechanisms of transport of quinapril in Caco-2 cell monolayers: comparison with cephalexin.

PURPOSE: To determine the transport mechanisms of quinapril and cephalexin in Caco-2 cell monolayers, a cell culture model of the human small intestinal epithelium. METHODS: Uptake, transepithelial transport and intracellular accumulations of these two drugs were measured using Caco-2 cell monolayers grown onto Millicells and magnetically stirred diffusion chambers. RESULTS: Transepithelial transport, apical (AP)4 uptake and intracellular accumulation of both drugs depended on the maintenance of a transepithelial proton gradient and temperature of the medium. However, quinapril transport and accumulation, which did not display a maximum at approximately pH 6, was more sensitive to proton gradient change, whereas cephalexin transport was more sensitive to concentration change (range 0.5-5 mM). In addition, quinapril (1 mM) transport was decreased significantly (p < 0.05) by 10 mM cephalexin, loracarbef, Gly-Pro and Phe-Pro, but not by enalapril; whereas cephalexin (0.1 mM) transport was decreased significantly (p < 0.05) by all four compounds. Similarly, AP quinapril (1 mM) uptake was also decreased by 10 mM loracarbef, Gly-Pro, cephalexin, and enalapril, but these inhibitory effects (20-50%) were quantitatively less than their inhibitory effects on cephalexin uptake (50-90%). Finally, the AP uptake of quinapril was also significantly (p < 0.05) inhibited by FCCP (10 micrograms/ml), amiloride (0.5 mM), DEP (0.5 mM), and staurosporine (5 nM). CONCLUSIONS: The transport of quinapril in the Caco-2 cells is via a combination of the carrier-mediated proton gradient-dependent peptide transporter and passive diffusion.

Amino Acid Sequence↗
PubMed1995

Bispecific antibodies as targeting agents for boron neutron capture therapy of brain tumors.

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10, a stable isotope, is irradiated with low energy (< or = 0.025 eV) or thermal neutrons to yield alpha particles and recoiling lithium-7 nuclei. A major requirement for the success of BNCT is the selective delivery of a sufficient number of boron atoms (approximately 10(9)) to individual cancer cells to sustain a lethal 10B (n, alpha) 7Li capture reaction. A panel of BsAb reactive with polyhedral borane anions (PBA) and a tumor-associated chondroitin sulfate proteoglycan has been produced. All of these BsAb showed strong reactivity with a panel of human glioblastoma and melanoma cell lines, as demonstrated by indirect membrane immunofluorescence. Two of them (H6 and B8) also reacted with cells that had been exposed to PBA (Na2B10H10 and Na2B12H11SH) and a boronated starburst dendrimer, which contained approximately 250-400 B atoms per molecule. The affinity constant (Ka) of BsAb-B8 was 2.57 x 10(8) M-1 on M21 human melanoma cell and 3.49 x 10(8) M-1 on A172 glioblastoma cells, which were almost identical to those of the parental monoclonal antibody (mAb) 9.2.27 on the same cell lines (2.62 x 10(8) M-1). Since our BsAb recognize both human glioblastoma and melanoma-associated antigens, as well as PBA, they potentially could be used to target 10B to these tumors for BNCT.

Animals↗
PubMed1995

Mutation analysis of the ROM1 gene in retinitis pigmentosa.

To examine the role of ROM1, a homologue of peripherin/RDS, in autosomal dominant retinitis pigmentosa (adRP), we screened 224 adRP and 29 simplex RP probands for ROM1 mutations. Four ROM1 alleles were designated as potentially pathogenic because they were found only in RP patients but not in 50-100 controls nor in 249 other RP probands. The substitutions P60T and T108M were present in a single allele in a subject with typical adRP, and this allele cosegregated with the disease in the small family. The putative null allele L114 [1 bp] was present in an individual with atypical RP but not in three unaffected siblings. This insertion has been previously reported to cause RP only when accompanied by a peripherin/RDS mutation, but no peripherin/RDS mutations were found in any of the four probands reported here. Two substitutions (G75D, R242Q) were present in two other probands with simplex RP. These data suggest that potentially pathogenic ROM1 mutations occur in 1% or less of patients with adRP or simplex RP. The absence of detectable peripherin/RDS mutations in these families suggests either that: (i) mutations in other digenic partners are required for pathogenic ROM1 alleles to cause retinal degeneration; (ii) these ROM1 mutations do not cause RP; or (iii) peripherin/RDS mutations are present but were not identified in these patients.

Adult↗
PubMed1995

Recombinant mapping of the familial hyperinsulinism gene to an 0.8 cM region on chromosome 11p15.1 and demonstration of a founder effect in Ashkenazi Jews.

A gene for autosomal recessive familial hyperinsulinism (HI) (OMIM: 256450), a neonatal metabolic disease characterized by inappropriate insulin secretion in the presence of severe hypoglycemia, was recently mapped to a 6.6 cM interval between the markers D11S926 and D11S928 on chromosome 11p in 15 families (1). In the current study we evaluated six additional families and five new markers, and further localized the gene between D11S419 and D11S1310. Using genotype data from CEPH Version 7 and data generated from this study, this region was estimated to be 0.8 cM in length. Significant linkage disequilibrium between markers and the HI gene was observed over a region of 10.3 cM (11 pter-D11S926-D11S1308-11pcen) for Ashkenazi Jewish chromosomes. Haplotype analysis showed that 12 of 36 HI chromosomes, versus one of 36 non-HI chromosomes, bore a specific haplotype for D11S419-D11S902-D11S921 (p < 0.0007), strongly suggesting a founder effect in this ethnic group.

Alleles↗
PubMed1995

Circadian rhythm adaptation to simulated night shift work: effect of nocturnal bright-light duration.

We compared bright-light durations of 6, 3 and 0 hours (i.e. dim light) during simulated night shifts for phase shifting the circadian rectal temperature rhythm to align with a 12-hour shift of the sleep schedule. After 10 baseline days there were 8 consecutive night-work, day-sleep days, with 8-hour sleep (dark) periods. The bright light (about 5,000 lux, around the baseline temperature minimum) was used during all 8 night shifts, and dim light was < 500 lux. This was a field study in which subjects (n = 46) went outside after the night shifts and slept at home. Substantial circadian adaptation (i.e. a large cumulative temperature rhythm phase shift) was produced in many subjects in the bright light groups, but not in the dim light group. Six and 3 hours of bright light were each significantly better than dim light for phase shifting the temperature rhythm, but there was no significant difference between 6 and 3 hours. Thus, durations > 3 hours are probably not necessary in similar shift-work situations. Larger temperature rhythm phase shifts were associated with better subjective daytime sleep, less subjective fatigue and better overall mood.

Adolescent↗
PubMed1995

Myocardial lipoprotein lipase activity: regulation by diabetes and fructose-induced hypertriglyceridemia.

The decrease in myocardial lipoprotein lipase (LPL) activity observed previously in acute, severe models of insulin-deficient diabetes may be a compensatory response to hypertriglyceridemia and a sustained increase in fatty acid delivery to cardiomyocytes. The administration of fructose (10% solution in the drinking water for 4 days) to rats produced hypertriglyceridemia, but heparin-releasable LPL activity from perfused hearts and total and heparin-releasable LPL activities in isolated cardiomyocytes were not reduced. The acute (4 day) induction of a mild diabetic state (60 mg/kg streptozotocin) resulted in modest hypertriglyceridemia, and a selective decrease in heparin-releasable LPL activity in perfused hearts; LPL activity in cardiomyocytes from diabetic rat hearts was not reduced. Therefore, the diabetes-induced fall in myocardial LPL activity is not secondary to hypertriglyceridemia, since fructose treatment did not change LPL activity. Perfusion of rat hearts with 100 microM lysophosphatidylcholine (LPC) released a small amount of LPL activity into the perfusate, but only if albumin was omitted from the perfusion solution. Thus, the selective reduction in heparin-releasable LPL activity in perfused diabetic hearts is probably not the consequence of displacement by LPC, a lipolytic product of the LPL-catalyzed degradation of triacylglycerol-rich lipoproteins. Circulating LPL activity in the plasma of diabetic rats was not decreased relative to control plasma enzyme activity; therefore, the reduction in heparin-releasable LPL activity is not because circulating LPL was less available for uptake by the endothelium in diabetic hearts.

Adipocytes↗
PubMed1995

Adult cardiomyocytes express functional high-affinity receptors for basic fibroblast growth factor.

As a first step in addressing the question of function for basic fibroblast growth factor (bFGF) in the adult myocardium, expression of bFGF receptors by adult rat myocytes was investigated. Cross-linking of 125I-labeled bFGF to purified sarcolemmal vesicles from adult hearts indicated specific binding to 90- to 104-kDa proteins, whereas equilibrium binding studies revealed the presence of "low"-affinity (1 nM) and "high"-affinity (115 pM) sites. Adult myocytes were found to express short and long variants of bFGF receptor 1 (FGFR-1, tyrosine kinase) mRNA. Adult heart overall levels of FGFR-1 mRNA were decreased by about one-third of corresponding fetal values. Several lines of evidence indicated that bFGF receptors in adult cardiomyocytes in situ and/or in isolation are functional. Isolated adult myocytes were found to be capable of heparin-resistant internalization of 125I-labeled bFGF, to lose their viability after interaction with bFGF-saporin (a mitotoxin known to kill cells after entry via the bFGF receptor), and to respond to bFGF by activation of mitogen-activated protein kinase. In addition, introduction of exogenous bFGF into the myocardium by Langendorff perfusion resulted in stimulation of tyrosine phosphorylation in association with cardiomyocyte intercalated disks, as assessed by immunofluorescence. It is concluded that adult cardiomyocytes express functionally coupled high-affinity bFGF receptors and that they are capable of a biologic response to bFGF in vivo.

Animals↗
PubMed1995

Cloning, genetic mapping, and expression analysis of a mouse renal sodium-dependent phosphate cotransporter.

Renal tubular reabsorption of phosphate is critical to the maintenance of phosphate homeostasis in mammals, and the brush-border membrane Na-P(i) cotransport systems in proximal tubules play a major role in this process. We have isolated a cDNA encoding a mouse sodium-dependent phosphate transport protein (Npt1), which is expressed primarily in the kidney. This protein is highly similar to its human and rabbit homologues, based on nucleotide and amino acid comparisons. The presence of potential Asn-linked glycosylation and protein kinase C phosphorylation sites that are conserved among all three homologues suggests that these sites may be important in the function and regulation of this protein. The Npt1 gene was mapped to mouse chromosome 13, close to the Tcrg locus. By both in situ hybridization and reverse transcription-polymerase chain reaction, Npt1 mRNA was localized predominantly to the proximal tubule.

Amino Acid Sequence↗
PubMed1995

Assignment of Tp53 and Tk1 to chromosome 13 in Peromyscus by fluorescence in situ hybridization.

Mus domesticus DNA probes for the tumor suppressor protein-53 (Tp53) and thymidine kinase-1 (Tk1) genetic loci were used to identify clones representing these loci in a Peromyscus leucopus (white-footed mouse) cosmid library. The cosmid-derived homologous probes were biotinylated and hybridized to P. maniculatus (deer mouse) chromosomes. Probes for both genes hybridized to the chromosome 13 pair identified by prior G-banding. Deer mouse chromosome 13 shares a region of homology with mouse chromosome 11, rat chromosome 10 and human chromosome 17.

Animals↗