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Biomedical subjects

X Liu

Publications and source records attributed to X Liu.

At least 523 records · Page 29Linked to original sources
PubMed2000

Targeting of human p53-overexpressing tumor cells by an HLA A*0201-restricted murine T-cell receptor expressed in Jurkat T cells.

A potent anti-human (hu) p53 CD8+ CTL response develops in HLA A*0201 transgenic (Tg) mice after immunization with peptides corresponding to HLA A*0201 motifs from hu p53. Mice immunized with the hu P53(149-157) peptide develop a CTL response that is of moderately high affinity and is capable of recognizing hu tumor cells expressing mutated p53. In this report, the mRNAs encoding the predominantly expressed T-cell receptor (TCR) sequences were molecularly cloned from a murine (mu) CTL clone derived from immunized Tg mice, which recognized endogenously processed hu p53 restricted by HLA A*0201. The separate A and B chain TCR cDNAs were transfected in the corresponding TCR A- and B- Jurkat-CD3- mutant T-cell lines, and each rescued CD3 surface expression. Both TCR chains were simultaneously introduced into Jurkat-CD3+ cells, and the transfected Jurkat cells recognized hu T2 cells sensitized with the p53(149-157) CTL epitope but not T2 cells sensitized with a nonspecific CTL epitope. Breast, pancreatic, and sarcoma tumor cell lines, which overexpress endogenous mutated p53, were recognized in the presence of anti-CD28 costimulation, only if they also expressed HLA A*0201. Normal hu fibroblasts established from skin cultures were not recognized. These results represent the first time that a p53-specific TCR capable of recognizing hu cancer cells was heterologously expressed in a naive recipient cell, converting that cell to one recognizing hu tumor cells with mutated p53. This TCR represents a candidate molecule for a genetic strategy in combating hu cancer by an adoptive immunotherapy approach, which uses the strong xenorecognition of hu p53 in mice.

Animals↗
PubMed2000

Prevalence and correlates of self-reported sleep problems among Chinese adolescents.

STUDY OBJECTIVES: This study examined the prevalence and correlates of sleep problems in Chinese adolescents. DESIGN AND SETTING: An epidemiological questionnaire survey was carried out in five high schools in Shandong Province of Mainland China. PARTICIPANTS: A total of 1365 adolescents between the ages of 12 and 18 years comprising 823 boys and 542 girls. MEASUREMENTS AND INTERVENTIONS: The participants completed a self-administered questionnaire regarding sleep duration, sleep problems, stressful life events, lifestyles, and personal and family characteristics. RESULTS: Mean sleep duration at night was 7.64 hours (SD = 0.86) and decreased with increasing age. Of the sample, 16.9% (95% CI = 13.2-20.5%) reported insomnia symptoms including difficulty initiating sleep (10.8%), difficulty maintaining sleep (6.3%), and early morning awakening (2.1%). Nightmares were reported more frequently by girls (chi2=20.09, p<0.001). Only 2.3% of the sample had ever taken hypnotic medication during the past month. Almost 22% of the subjects went to bed later than 12:00 PM at least once a week. Multiple logistic regression analysis showed that greater age, being at senior high school, doing no habitual physical exercise, poor physical health, self-selection of diet, longer distance from home to school, and life stress experienced during the past 12 months were significantly associated with an increased risk of insomnia. CONCLUSIONS: Self-reported sleep problems in Chinese adolescents are common and associated with multiple factors. These findings suggest the need for comprehensive programs to prevent sleep problems in adolescents.

Adolescent↗
PubMed2000

An epidemiological study of insomnia among the Japanese general population.

The study examined the prevalence and correlates of insomnia in a representative sample (n=3030) from the general population of Japan. Using a structured questionnaire, we found that the overall prevalence of insomnia during the preceding month was 21.4%, including difficulty initiating sleep (DIS: 8.3%), difficulty maintaining sleep (DMS: 15.0%), and early morning awakening (EMA: 8.0%). Multiple logistic regression analysis showed that older age, being unemployed, lack of habitual exercise, poor perceived health, psychological stress, and being unable to cope with stress were associated with an increased prevalence of insomnia. These findings indicate that the prevalence of insomnia in the general population of Japan is comparable to that reported in Western countries, and that insomnia is associated with multiple psychosocial factors.

Adult↗
PubMed2000

Secondary amides of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid as inhibitors of pyruvate dehydrogenase kinase.

N'-methyl-N-(4-tert-butyl-1,2,5,6-tetrahydropyridine)thiourea, SDZ048-619 (1), is a modest inhibitor (IC(50) = 180 microM) of pyruvate dehydrogenase kinase (PDHK). In an optimization of the N-methylcarbothioamide moiety of 1, it was discovered that amides with a small acyl group, in particular appropriately substituted amides of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid, are inhibitors of PDHK. Utilizing this acyl moiety, herein is reported the rationale leading to the optimization of a series of acylated piperazine derivatives. Methyl substitution of the piperazine at the 2- and 5-positions (with S and R absolute stereochemistry) markedly increased the potency of the lead compound (>1,000-fold). Oral bioavailability of the compounds in this series is good and is optimal (as measured by AUC) when the 4-position of the piperazine is substituted with an electron-poor benzoyl moiety. (+)-1-N-[2,5-(S, R)-Dimethyl-4-N-(4-cyanobenzoyl)piperazine]-(R)-3,3, 3-trifluoro-2-hydroxy-2-methylpropanamide (14e) inhibits PDHK in the primary enzymatic assay with an IC(50) of 16 +/- 2 nM, enhances the oxidation of [(14)C]lactate into (14)CO(2) in human fibroblasts with an EC(50) of 57 +/- 13 nM, diminishes lactate significantly 2.5 h post-oral-dose at doses as low as 1 micromol/kg, and increases the ex vivo activity of PDH in muscle, liver, and fat tissues in normal Sprague-Dawley rats. These PDHK inhibitors, however, do not lower glucose in diabetic animal models.

Amides↗
PubMed2000

Ultraviolet damage and nucleosome folding of the 5S ribosomal RNA gene.

The Xenopus borealis somatic 5S ribosomal RNA gene was used as a model system to determine the mutual effects of nucleosome folding and formation of ultraviolet (UV) photoproducts (primarily cis-syn cyclobutane pyrimidine dimers, or CPDs) in chromatin. We analyzed the preferred rotational and translational settings of 5S rDNA on the histone octamer surface after induction of up to 0.8 CPD/nucleosome core (2.5 kJ/m(2) UV dose). DNase I and hydroxyl radical footprints indicate that UV damage at these levels does not affect the average rotational setting of the 5S rDNA molecules. Moreover, a combination of nuclease trimming and restriction enzyme digestion indicates the preferred translational positions of the histone octamer are not affected by this level of UV damage. We also did not observe differences in the UV damage patterns of irradiated 5S rDNA before or after nucleosome formation, indicating there is little difference in the inhibition of nucleosome folding by specific CPD sites in the 5S rRNA gene. Conversely, nucleosome folding significantly restricts CPD formation at all sites in the three helical turns of the nontranscribed strand located in the dyad axis region of the nucleosome, where DNA is bound exclusively by the histone H3-H4 tetramer. Finally, modulation of the CPD distribution in a 14 nt long pyrimidine tract correlates with its rotational setting on the histone surface, when the strong sequence bias for CPD formation in this tract is minimized by normalization. These results help establish the mutual roles of histone binding and UV photoproducts on their formation in chromatin.

Animals↗
PubMed2000

Small angle X-ray scattering studies on local structure of tobacco mosaic virus RNA in solution.

Effects of temperature and ionic strength (S) on the local structure of tobacco mosaic virus RNA in phosphate buffer solution are studied by analyzing the small-angle X-ray scattering (SAXS) curves. The root-mean-square radius of a cross-section of RNA chain was kept at 0.845+/-0.005 nm over a wide range of S from 0.2 to 0.003 at 20 degrees C, whereas it gradually diminished from 0.85 to 0.61 nm when the temperature is raised from 20 to 50 degrees C at S = 0.2. Nevertheless, all of SAXS curves reflecting the backbone structures were equally mimicked by theoretical ones of freely hinged rod (FHR) models, i.e. several straight rods joined with freely hinged joints in the form of a combination of the letter Y, if the constituent rod lengths in the models are adjusted. From these facts, it is suggested that the local structure of the RNA chain in aqueous solution is characterized by an essential feature that unpaired bases in the partially double-stranded helix are constantly far isolated from each other along the helix and the rod-like structure of the helix is preserved over a range of helical contents. Such a characteristic local structure of the chain is entirely collapsed in the formamide solution at 50 degrees C.

Buffers↗
PubMed2000

Enhanced type I immune response to a hepatitis B DNA vaccine by formulation with calcium- or aluminum phosphate.

DNA vaccines induce protective humoral and cell-mediated immune responses in several animal models. When compared with conventional vaccines, however, DNA vaccines often induce lower antibody titers. We have now found that formulation of a DNA vaccine encoding hepatitis B surface antigen with calcium- or aluminum phosphate adjuvants can increase antibody titers by 10-100-fold and decrease the immunogenic dose of DNA by 10-fold. Furthermore, boosting an HBs protein-primed response with the adjuvanted DNA vaccine resulted in a dramatic increase in the HBs-specific IgG2a response reflecting a shift towards a TH1 response. The mechanism by which aluminum phosphate exerts its adjuvant effect is not through increased expression of HBsAg in vivo; rather, the adjuvant appears to increase the number and affinity of HBs peptide antigen-specific IFN-gamma and IL-2 secreting T cells.

Adjuvants, Immunologic↗
PubMed2000

Studies on C-phycocyanin from Cyanidium caldarium, a eukaryote at the extremes of habitat.

C-Phycocyanin, a biliprotein, was purified from the red alga, Cyanidium caldarium. This alga grows at temperatures up to 57 degrees C, a very high temperature for a eukaryote, and at pH values down to 0.05. Using the chromophores on C-phycocyanin as naturally occurring reporter groups, the effects of temperature on the stability of the protein were studied by circular dichroism and absorption spectroscopy. The protein was unchanged from 10 to 50 degrees C, which indicates that higher temperatures are not required to cause the protein to be photosynthetically active. At 60 and 65 degrees C, which are above the temperatures at which the alga can survive, the protein undergoes irreversible denaturation. Gel-filtration column chromatography demonstrated that the irreversibility is caused by the dissociation of the trimeric protein to its constitutive polypeptides. Upon cooling, the alpha and beta polypeptides did not reassemble to the trimer. Unlike phycocyanins 645 and 612, the C-phycocyanin does not show a reversible conformational change at moderately high temperatures. At constant temperature, the C-phycocyanin was more stable than a mesophilic counterpart. It is designated a temperature-resistant protein.

Circular Dichroism↗
PubMed2000

Seven non-contiguous intracellular residues of the lutropin/choriogonadotropin receptor dictate the rate of agonist-induced internalization and its sensitivity to non-visual arrestins.

The amino acid sequences of the human (h) and rat (r) lutropin/choriogonadotropin receptors (LHR) are 87% identical, but the rate of agonist-induced internalization of the hLHR is approximately 7 times faster than that of the rLHR. Chimeras of the hLHR and the rLHR showed that this rate is dictated by the serpentine domain and the cytoplasmic tail. Further mutational analysis identified seven residues, two adjacent residues in the second intracellular loop (Val/Gln in the rLHR and Ile/His in the hLHR), four non-contiguous residues in the third intracellular loop (Arg/Gln/Thr/Pro in the rLHR and Lys/Arg/Met/Thr in the hLHR), and one in the C-terminal tail (Leu in the rLHR and Phe in the hLHR), that are necessary and sufficient to impart the slow rate of internalization of the rLHR and the fast rate of internalization of the hLHR. The internalization of the rLHR and the hLHR display different sensitivities to the non-visual arrestins. Therefore, we also tested if the simultaneous exchange of these seven residues resulted in the exchange of this property. Since this was found to be the case, we propose that these seven residues identified here form a non-visual arrestin-binding site.

Amino Acid Sequence↗
PubMed2000

Molecular and clinical study of spinocerebellar ataxia type 7 in Chinese kindreds.

OBJECTIVE: To investigate the clinical and molecular characteristics of spinocerebellar ataxia type 7 (SCA7) in Chinese kindreds. BACKGROUND: Spinocerebellar ataxia type 7 is caused by the expansion of an unstable CAG repeat in the first exon of the SCA7 gene. METHODS: Clinical and related examinations were performed in all affected or at-risk individuals from 4 Chinese families presenting with autosomal dominant cerebellar ataxia and decreased visual acuity. The size of the (CAG)(n) array of the SCA7 gene was detected by polymerase chain reaction, polyacrylamide gel electrophoresis, and related techniques in the 4 families and 67 healthy controls. The relationship between expanded repeat number and age of onset was statistically analyzed. RESULTS: The SCA7 mutation was identified in 2 families. Clinical study revealed that great variation occurred in the age of onset, initial symptoms, and associated signs. Meanwhile, the analysis of 11 parent-child couples demonstrated the existence of marked anticipation. Some distinct retinal changes were noted in 2 affected patients. All SCA7 patients in our series exhibited expanded CAG repeats, ranging from 44 to 85 repeats, with a strong negative correlation between repeat size and age of onset. Repeat lengths of expanded alleles showed somatic mosaicism in leukocyte DNA. There were some subtle clinical differences between the SCA7-positive and -negative cases. CONCLUSIONS: Clinical variation occurred not only among the SCA7 families but also within the same kindred. Meiotic and mitotic instability of the CAG repeat in the SCA7 gene were demonstrated, and intergenerational instability of the array was associated with the clinical phenomenon of anticipation. Arch Neurol. 2000;57:1513-1518

Adolescent↗
PubMed2000

Severe peripheral sensory neuron loss and modest motor neuron reduction in mice with combined deficiency of brain-derived neurotrophic factor, neurotrophin 3 and neurotrophin 4/5.

Neurotrophins are a family of structurally and functionally related proteins that regulate neuronal survival during development. In the peripheral nervous system (PNS), both in vitro and in vivo studies have shown that neurotrophins are potent factors for the survival of various sensory neurons and sympathetic neurons. However, it is not clear whether all PNS neurons are neurotrophin-dependent. In the central nervous system (CNS), studies using injury models show that neurotrophins promote the survival of CNS neurons. But mice lacking individual neurotrophins or a combination of BDNF and NT4 did not show significant CNS neuronal loss. Here we derived mice lacking three neurotrophins, brain-derived growth factor (BDNF), neurotrophin-3 (NT3), and neurotrophin-4 (NT4) to study the effect of triple neurotrophin deficiency on peripheral and central neurons. These triple-deficient mice did not nurse and died within 12 hours after birth. Neuronal cell counts showed that triple mutant pups lacked most of their peripheral sensory neurons and had a statistically significant reduction of motor neurons in several motor nuclei. Our results suggest that neurotrophins are essential for the survival of most peripheral sensory neurons and affect the survival of a small portion of motor neurons during embryogenesis.

Animals↗
PubMed2000

Regulation of (1-3)-beta-glucan-stimulated Ca(2+) influx by protein kinase C in NR8383 alveolar macrophages.

Stimulation of (1-3)-beta-glucan receptors results in Ca(2+) influx through receptor-operated channels in alveolar macrophages (AMs), but the mechanism(s) regulating Ca(2+) influx is still undefined. In this study we investigated the role of protein kinase C (PKC) regulation of Ca(2+) influx in the NR8383 AM cell line using the particulate (1-3)-beta-glucan receptor agonist zymosan. PKC inhibition with calphostin C (CC) or bisindolymaleimide I (BSM) significantly reduced zymosan-induced Ca(2+) influx, whereas activation of PKC with phorbol-12-myristate 13-acetate (PMA) or 1, 2-dioctanoyl-sn-glycerol (DOG) mimicked zymosan, inducing a concentration-dependent Ca(2+) influx. This influx was dependent on extracellular Ca(2+) and inhibited by the receptor-operated Ca(2+) channel blocker SK&F96365, indicating that zymosan and PKC activate Ca(2+) influx through a similar pathway. NR8383 AMs expressed one new PKC isoform (delta) and two atypical PKC isoforms (iota and lambda), but conventional PKC isoforms were not present. Stimulation with zymosan resulted in a translocation of PKC-delta from the cytosol to the membrane fraction. Furthermore, inhibition of protein tyrosine kinases (PTKs) with genistein prevented zymosan-stimulated Ca(2+) influx and PKC-delta translocation. These results suggest that PKC-delta plays a critical role in regulating (1-3)-beta-glucan receptor activated Ca(2+) influx in NR8383 AMs and PKC-delta translocation is possibly dependent on PTK activity.

Animals↗
PubMed2000

Diastereoselectivity an chiral ruthenium complexes of chiraphos monoxide ligands: epimerization, quasiracemates, and Lewis acid catalysis.

Heterobidentate chelating ligands comprising P,O-donor sets produce chiral metal centers when bound to arene-ruthenium complexes. The cymene complex [CyRu(eta2-chelate-P,O)Cl]+ cations are precursors to 16-electron dicationic strong Lewis acids which have potential use in asymmetric catalysis. Sixteen-electron complexes of this type, however, also provide a pathway with a low energy barrier to epimerization of the metal center in intermediates. With the chiral ligand (R,R)-chiraphos monoxide, the metal center in [CyRu(eta2)-(R,R)-Ph2PCHMeCHMe Ph2PO-P,O)Cl]+ epimerizes to minimize steric interactions in the two diastereomers yielding a 8. 2:1 dr in solution. Nevertheless, upon crystallization a new equilibrium is obtained in the solid and the crystals obtained have a 1:1 dr. These crystals are quasiracemates, which contain equal amounts of the (RRu) and (SRu)-CyRu-P-O-Cl stereocenters within the same crystal. The doubly charged Lewis acid, [CyRu(eta2-(R, R)-Ph2PCHMeCHMe Ph2PO-P,O)(solvate)]2+ derived from the chloro complex by chloride abstraction with AgSbF6 gave modest ee's (30%) in the Diels-Alder reaction of methacrolein with cyclopentadiene.

Acetonitriles↗
PubMed2000

Identification of a 1-megabase consensus region of deletion at 1p36.3 in primary neuroblastomas.

BACKGROUND: Deletion of the distal short arm of chromosome 1 occurs frequently in neuroblastoma. In addition, neuroblastoma has been described in children with constitutional deletions within 1p36, supporting the existence of one or more neuroblastoma suppressor genes within this region. PROCEDURE: We have pursued a 1p36 tumor suppressor gene identification strategy that has included deletion mapping of 566 primary neuroblastomas and 46 neuroblastoma-derived cell lines, and have determined the parental origin of the deleted 1p homologue in 44 cases to determine whether there is evidence for genomic imprinting within this region. RESULTS AND CONCLUSIONS: We have identified a 1-Mb consensus region of deletion within 1p36.3 defined by primary tumor deletions, constructed a physical map of the region that is being sequenced to completion, and have identified and prioritized candidate genes within this region for further analyses.

Alleles↗
PubMed2000

BIN1 inhibits colony formation and induces apoptosis in neuroblastoma cell lines with MYCN amplification.

BACKGROUND: MYCN amplification and overexpression occurs in 25% of neuroblastomas and independently predicts for poor prognosis disease, an effect thought to be mediated by its role as a transcriptional activator of growth promoting genes. However, in many mammalian cells, deregulated expression of MYC family genes (including MYCN) induces apoptosis. We hypothesized that BIN1, a MYC interacting protein capable of inducing apoptosis, may be an important regulator of MYCN in neuroblastoma. RESULTS: BIN1 expression was found to be reduced in MYCN-amplified cell lines. Further, forced expression of BIN1 markedly reduced colony formation in MYCN-amplified, but not single-copy, cell lines. This effect appeared to be caused by an increase in apoptosis, and was augmented by serum deprivation and concurrent cytotoxic drug therapy in cell culture CONCLUSION: BIN1 inactivation may be necessary for MYCN overexpression to lead to cellular proliferation rather than programmed cell death in neuroblastomas with MYCN amplification.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Copper induces apoptosis in BA/F3beta cells: Bax, reactive oxygen species, and NFkappaB are involved.

Copper, an essential trace element, can be toxic to some cells when present in excess. But thorough investigations into the cytotoxicity of copper and subsequent molecular mechanisms are rare, although the cytotoxicity of copper has been applied to cancer chemotherapy. The present study demonstrates that Cu(2+) inhibits [(3)H] thymidine incorporation in mouse pro-B cell line BA/F3beta and induces apoptosis. Apoptosis was mainly judged by morphology of cells, quantification of subdiploid DNA contents by flow cytometry, and detection of DNA fragmentation by gel electrophoresis. The apoptotic effect is dose and time dependent. Western blotting shows Bax is upregulated by Cu(2+). Bcl-2 overexpression can partially inhibit this apoptosis. Moreover, Cu(2+) increases the production of reactive oxygen species (ROS) in a dose-dependent manner. The antioxidant N-acetylcysteine (NAC) not only significantly inhibited copper-induced apoptosis but also totally blocked generation of ROS, while Bcl-2 overexpression has no effect on the generation of ROS. Furthermore, our results show that NFkappaB is downregulated by Cu(2+). Bcl-2 overexpression or NAC can sustain the activity of NFkappaB. These data indicate that Cu(2+) might induce apoptosis in BA/F3beta cells via upregulation of Bax and ROS and subsequent inactivation of NFkappaB.

Acetylcysteine↗
PubMed2000

Life events, locus of control, and behavioral problems among Chinese adolescents.

This study examined associations of life events and locus of control with behavioral problems among 1,365 Chinese adolescents by using the Youth Self-Report (YSR), Adolescent Self-Rating Life Events Checklist (ASLEC), and the Nowicki-Strickland Locus of Control Scale for Children. Results indicated that the overall prevalence of behavioral and emotional problems was 10.7% (95% CI = 9.9-11.5%). Logistic-regression analyses showed that a total of 13 negative life events mainly coming from academic domain and interpersonal relationships, high life-stress score, and high external locus score significantly increased the risk for behavioral problems. Life stress and locus of control significantly interacted with behavioral problems. These findings support the linkage between stressful life events and psychopathology in a general population of adolescents from mainland China, and demonstrate the stress-moderating effects of locus of control on psychopathology as well.

Adolescent↗