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Biomedical subjects

W Liu

Publications and source records attributed to W Liu.

At least 307 records · Page 17Linked to original sources

Characterization of a murine monoclonal antibody that mimics heparin-induced thrombocytopenia antibodies.

Antibodies to PF4/heparin can be demonstrated in almost all patients with heparin-induced thrombocytopenia/thrombosis (HIT/HITT) and in some persons exposed to heparin who do not have clinical manifestations. The role of anti-PF4/heparin antibodies in the pathogenesis of HIT/HITT has been difficult to establish because the antibodies found in serum are generally polyclonal and polyspecific. To circumvent this problem, we developed a murine monoclonal antibody (mAb) to human (h) PF4/heparin complexes. A monoclonal IgG(2bkappa )antibody (designated KKO) was identified that bound specifically to hPF4/heparin complexes. Maximal binding of KKO to hPF4/heparin complexes occurred at similar molar ratios of PF4:heparin observed for HIT/HITT antibodies. KKO also bound to hPF4 in association with other glycosaminoglycans. Platelet activation by KKO required heparin and was abrogated by blockade of FcgammaRIIA. In the presence of PF4, KKO bound to endothelial cells, but not to CHO cells lacking heparan sulfate proteoglycans. Variants of PF4 complexed to heparin were recognized equally well by KKO and HIT/HITT sera. KKO competes for binding with a subset of HIT/HITT antibodies that are relatively spared by mutations in the 3rd domain of PF4. The nucleotide and predicted amino acid sequences of KKO and RTO, a murine anti-hPF4 mAb that does not require heparin for binding, revealed no obvious relationship in either the heavy- or the light-chain immunoglobulin variable regions. These studies suggest that KKO recapitulates the antigenic and functional specificity of a subset of HIT/HITT antibodies and may, therefore, provide insight into the pathogenesis of thrombocytopenia and thrombosis in affected persons. (Blood. 2000;95:1533-1540)

Amino Acid Sequence↗

Opioids suppress IPSCs in neurons of the rat medial septum/diagonal band of Broca: involvement of mu-opioid receptors and septohippocampal GABAergic neurons.

The medial septum/diagonal band region (MSDB), which provides a major cholinergic and GABAergic input to the hippocampus, expresses a high density of opioid receptors. Behaviorally, intraseptal injections of opioids produce deficits in spatial memory, however, little is known about the electrophysiological effects of opioids on MSDB neurons. Therefore, we investigated the electrophysiological effects of opioids on neurons of the MSDB using rat brain slices. In voltage-clamp recordings with patch electrodes, bath-applied met-enkephalin, a nonselective opioid receptor agonist, decreased the number of tetrodotoxin and bicuculline-sensitive inhibitory synaptic currents in cholinergic- and GABA-type MSDB neurons. A similar effect occurred in brain slices containing only the MSDB, suggesting that opioids decrease GABA release primarily by inhibiting spontaneously firing GABAergic neurons located within the MSDB. Accordingly, in extracellular recordings, opioid-sensitive, spontaneously firing neurons could be found within the MSDB. Additionally, in intracellular recordings a subpopulation of GABA-type neurons were directly inhibited by opioids. All effects of met-enkephalin were mimicked by a mu receptor agonist, but not by delta or kappa agonists. In antidromic activation studies, mu-opioids inhibited a subpopulation of septohippocampal neurons with high conduction velocity fibers, suggestive of thickly myelinated GABAergic fibers. Consistent with the electrophysiological findings, in double-immunolabeling studies, 20% of parvalbumin-containing septohippocampal GABA neurons colocalized the mu receptor, which at the ultrastructural level, was found to be associated with the neuronal cell membrane. Thus, opioids, via mu receptors, inhibit a subpopulation of MSDB GABAergic neurons that not only make local connections with both cholinergic and noncholinergic-type MSDB neurons, but also project to the hippocampus.

Animals↗

Congenital absence of permanent teeth in a six-generation Chinese kindred.

We report on rare, heritable, permanent tooth agenesis in a large Chinese kindred. The congenital absence of permanent teeth except the first and second accessory teeth was observed in 52 individuals through six successive generations in the kindred comprising 328 members. Clinical assessments were carried out, and inheritance mode and spousal influence of the anomaly on their offspring were analyzed. Consequently, the anomaly was transmitted in an autosomal dominant fashion with incomplete penetrance (P = 0.88), and no significant clinical manifestations other than the oligodontia were found. A geographical or environmental effect on the affected individuals was obviously eliminated, because any who are related to the kindred but live under the same conditions are fully healthy. The disorder we describe, therefore, differs from any previously reported oligodontia/anodontia syndromes. The oligodontia ranged from a few teeth to the whole set of teeth, and usually occurred at a period from age 7 or 8 years, the time when primary teeth are normally replaced by permanent teeth, to the forties. Roentgenography of the affected persons indicated that only the first and/or second accessory teeth with tooth buds developed as permanent teeth. In fact, the diphyodontic germination sometimes occurred in the oral cavity of the affected individuals.

China↗

Comparative spectroscopic and electrochemical properties of bis(octakis(dodecylthio)naphthalocyaninato)europium(III) and bis(tetra-tert-butylnaphthalocyaninato)europium(III) complexes.

Bis(substituted-2,3-naphthalocyaninato)europium(III) complexes: bis(octakis(dodecylthio)-2,3-naphthalocyaninato)europium(III) (Eu[2,3-Nc(SC12H25)8]2, 1) and bis(tetra-tert-butyl-2,3- naphthalocyaninato)europium(III) (Eu[2,3-Nc(t-Bu)4]2, 2) have been synthesized by cyclic tetramerization of naphthalonitriles with Eu(acac)3.H2O in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in refluxing n-octanol. These compounds were characterized by UV-visible, magnetic circular dichroism (MCD), near-IR, IR, EPR, and mass spectroscopies. The absorption and MCD spectra of 1 showed splitting of the Q band, with peaks at 700 and 784 nm, red shifted from the Q band of 2 at 763 nm. The absorption and MCD spectral band deconvolution calculations of complex 1 gave two A terms in the Q-band region. The A terms are assigned to 2A2-->2E1 transitions. Cyclic voltammograms of 1 and 2 showed reversible oxidation couples at E1/2 = -0.28 V (for 2) and -0.25 V (for 1) vs ferrocenium/ferrocene (Fc+/Fc). The second oxidation exhibited a complicated behavior for both complexes. The reduction couples for 2 were observed at E1/2 = -0.61, -1.64, -1.97, and -2.42 V, and for 1 they were observed at E1/2 = -0.62, -1.60, -1.86, and -2.27 V vs Fc+/Fc. Spectral changes observed on chemical oxidation and reduction of the complexes are presented, and the behaviors of 1 and 2 are compared.

Journal Article↗

Treatment with all-trans-retinoic acid decreases levels of endogenous TGF-beta(1) in the mesenchyme of the developing mouse inner ear.

BACKGROUND: Previous studies have shown that in utero exposure of the mouse embryo to high doses of all-trans-retinoic acid (atRA) produces defects of the developing inner ear and its surrounding cartilaginous capsule, while exposure of cultured periotic mesenchyme plus otic epithelium to high doses of exogenous atRA results in an inhibition of otic capsule chondrogenesis. METHODS: In this study, we examine the effects of atRA exposure on the endogenous expression of transforming growth factor-beta(1) (TGF-beta(1)), a signaling molecule that mediates the epithelial-mesenchymal interactions that guide the development of the capsule of the inner ear. RESULTS: Our results demonstrate a marked reduction in immunostaining for TGF-beta(1) in the periotic mesenchyme of atRA-exposed embryos of age E10.5 and E12 days in comparison with control specimens. Consistent with these in vivo findings, high-density cultures of E10.5 periotic mesenchyme plus otic epithelium, treated with doses of atRA that suppress chondrogenesis, showed significantly decreased levels of TGF-beta(1), as compared with TGF-beta(1) levels in untreated control cultures. Furthermore, we demonstrate a rescue of cultured periotic mesenchyme plus otic epithelium from atRA-induced chondrogenic suppression by supplementation of cultures with excess TGF-beta(1). CONCLUSIONS: Our results support the hypothesis that TGF-beta(1) plays a role in mechanisms of atRA teratogenicity during inner ear development.

Animals↗

Specific expression of the LIM/homeodomain protein Lim-1 in horizontal cells during retinogenesis.

The LIM/homeodomain transcription factor Lim-1 has been shown to play an essential role in early embryonic patterning during vertebrate development. Here we report the spatial and temporal expression patterns of Lim-1 during retinal development as detected by immunohistochemistry using a specific anti-Lim-1 antibody. By double-immunostaining, we have demonstrated for the first time that Lim-1 is exclusively expressed within the horizontal cell type in the adult retina. In the developing mouse retina, Lim-1 commences its expression in migratory horizontal cell precursors streaming toward the future horizontal cell layer in the ventricular zone. Moreover, its expression during retinogenesis is spatially and temporally coincident with that of the calcium-binding protein calbindin D-28k in horizontal cells. These data together suggest a possible role for Lim-1 in terminal differentiation and maintenance of horizontal cells, and that Lim-1 can serve as a specific molecular marker for the study of horizontal cell specification.

Animals↗

Loss of expression of the DRR 1 gene at chromosomal segment 3p21.1 in renal cell carcinoma.

Consistent deletion of DNA sequences in chromosomal band 3p21 observed in a variety of human tumors suggests the presence of one or more tumor suppressor genes within this region. Previously, we reported on the construction of two distinct cosmid contigs and our identification of several new genes within 3p21.1. In our search for tumor suppressor genes from this region, we have cloned a gene that we have called DRR 1 (downregulated in renal cell carcinoma). The gene was first mapped to 3p21.1 by fluorescence in situ hybridization analysis. Further analysis of yeast artificial chromosome clones in 3p14.2-p21.1 refined its localization. DRR 1 spans about 10 Kb of genomic DNA with a 3.5-Kb mature transcript. The putative protein encoded by this gene is 144 amino acids and includes a nuclear localization signal and a coiled domain. The gene showed loss of expression in eight of eight renal cell carcinoma cell lines, one of seven ovarian cancer cell lines, one of one cervical cancer cell line, one of one gastric cancer cell line, and one of one non-small-cell lung cancer cell line. Southern blot analysis did not show any altered bands, indicating that gross structural changes or deletions did not cause the loss of expression. This gene was also found to have reduced expression in 23 of 34 paired primary renal cell carcinomas. Mutational analysis detected three polymorphic sites within the gene, but no point mutations were identified in the 34 primary tumors. However, we did detect base substitutions in 4 of 12 cell lines that had undetectable expression of the gene. We also transfected the gene into DRR 1-negative cell lines and observed clear growth retardation. Our results suggest that loss of expression of the DRR 1 gene may play an important role in the development of renal cell carcinoma and possibly other tumors. Genes Chromosomes Cancer 27:1-10, 2000.

Amino Acid Sequence↗

Human acid ceramidase is overexpressed but not mutated in prostate cancer.

The human acid ceramidase gene, that causes Farber disease, is located in 8p22, a region frequently altered in several cancers, including prostate cancer. Acid ceramidase catalyzes the hydrolysis of ceramide, a potent lipid second messenger molecule that promotes apoptosis and inhibits cellular proliferation. It is not known whether this gene, or its expression, is altered in prostate cancer. Here, we report the structural organization of the human gene, its expression in human tissues, and the identification of several single nucleotide polymorphisms. No cancer-related mutations were found in the gene in a panel of prostate tumor DNAs analyzed, but increased expression was observed in prostate tumor tissues when compared with matched normals. This increase was observed in all three prostate tumor cell lines tested (DU145, LnCAP, and PC3) when compared to a BPH (benign prostatic hyperplasia) cell line and 15/36 prostate tumors. These results suggest that acid ceramidase may play an important role in prostate carcinogenesis.

Acid Ceramidase↗

Phylogeny of east asian bufonids inferred from mitochondrial DNA sequences (Anura: amphibia).

We investigated the relationships of Asian bufonids using partial sequences of mitochondrial DNA genes. Twenty-six samples representing 14 species of Bufo from China and Vietnam and 2 species of Torrentophryne from China were examined. Three samples of Bufo viridis from Armenia and Georgia were also sequenced to make a comparison to its sibling tetraploid species B. danatensis. Bufo americanus, from Canada, was used as the outgroup. Sequences from the 12S ribosomal RNA, 16S ribosomal RNA, cytochrome b, and the control region were analyzed using parsimony. East Asian bufonids were grouped into two major clades. One clade included B. andrewsi, B. bankorensis, B. gargarizans, B. tibetanus, B. tuberculatus, its sister clade B. cryptotympanicus, and the 2 species of Torrentophryne. The second clade consisted of B. galeatus, B. himalayanus, B. melanostictus, and a new species from Vietnam. The placement of three taxa (B. raddei, B. viridis, and its sister species, B. danatensis) was problematic. The genus Torrentophryne should be synonymized with Bufo to remove paraphyly. Because B. raddei does not belong to the clade that includes B. viridis and B. danatensis, it was removed from the viridis species group. The species status of B. bankorensis from Taiwan is evaluated.

Animals↗

Study on the effect of ligustrazine on hematopoietic reconstitution in bone marrow transplantation mice.

To explore the effects of ligustrazine on hematopoietic reconstitution and its mechanism after bone marrow transplantation (BMT), the allogenic BMT mice were given intra-abdominal injection of 2 mg ligustrazine twice a day. On the 1st, 7th, 14th, and 28th day after BMT, peripheral blood cells and bone marrow nuclear cells (BMNC) were counted, and the histological features were evaluated. On the 7th, 14th, 21st day after BMT, CXCR4 expression on the BMNC was assayed. The results showed that peripheral blood cell counts and BMNC counts in ligustrazine-treated group on the 7th, 14th, 28th day were higher than those in BMT group (P < 0.01 or P < 0.05). The percentage of hematopoietic tissue volume, fat tissue hyperplasia and congestion and dilation degree of microvessel in ligustrazine-treated group on the 7th, 14th, 21st, 28th day was higher than those in BMT group. The CXCR4 expression levels in ligustrazine-treated group were higher than in BMT group (P < 0.01 or P < 0.05) on the 7th and 14th day, and were lower than in BMT group on the 21st day (P < 0.01). It is concluded that the ligustrazine can accelerate hematopoietic reconstruction, enhance growth of hematopoietic tissues and promote the repair of microvessels. The CXCR4 expression levels on BMNC may be responsible for the effect of ligustrazine.

Animals↗

Multiple defects of cell cycle checkpoints in U937-ASPI3K, an U937 cell mutant stably expressing anti-sense ATM gene cDNA.

(Ataxia-telangiectasia mutated gene (ATM) functions in control of cell cycle checkpoints in responding to DNA damage and protects cells from undergoing apoptosis. Knock-out within tumor cells of endogenous ATM will achieve therapeutic benefits and enable a better understanding of the decisive mechanisms of cell death or survival in response to DNA damaging agents.) In present paper, we sought to characterize the cell cycle checkpoint profiles in U937-ASPI3K, a U937 cell mutant that was previously established with endogenous ATM knock-out phenotype. Synchronized U937-ASPI3K was exposed to 137Cs irradiation, G1, S, G2/M cell cycle checkpoint profiles were evaluated by determining cell cycle kinetics, p53/p21 protein, cyclin dependent kinase 2 (CDK2) and p34CDC2 kinase activity in response to irradiation. U937-ASPI3K exhibited multiple defects in cell cycle checkpoints as defined by failing to arrest cells upon irradiation. The accumulation of cellular p53/p21 protein and inhibition of CDK kinase was also abolished in U937-ASPI3K. It was concluded that the stable expression of anti-sense PI3K cDNA fragment completely abolished multiple cell cycle checkpoints in U937-ASPI3K, and hence U937-ASPI3K with an AT-like phenotype could serves as a valuable model system for investigating the signal transduction pathway in responding to DNA damaging-based cancer therapy.

Apoptosis↗

Study on biologic activity for membrane of normal bone marrow cells with infection of epidemic hemorrhagic fever virus.

Using DPH fluorescence probe, the membrane of normal bone marrow cells with infection of epidemic hemorrhagic fever virus (EHFV) was labeled. The membrane lipid fluidity was obviously decreased from the membrane lipid fluorescence polarization. The membrane lipid fluidity of lymphocyte, monocyte and neutrophilic granulocyte was dynamically observed. After culturing the cells for 1, 6, 24 and 72 h, it was found that all the membrane lipid fluidity of the infected cells was decreased obviously with the longer the culturing time, the more obvious it. Compared with the normal control groups, there was a significant difference statistically (P < 0.05-0.01). It was suggested that the decrease of the membrane lipid fludity of normal bone marrow cell with infection of EHFV had correlation with the degree of virus invading and cell-function injury.

Bone Marrow Cells↗

Identification of differentially expressed genes in nasopharyngeal carcinoma by means of the Atlas human cancer cDNA expression array.

PURPOSE: To investigate genes of critical areas, including cell cycle/growth control, apoptosis, oncogene/tumor suppressors and growth factor/cytokines, that are differentially expressed in nasopharyngeal carcinoma. METHODS: The Human Cancer cDNA Atlas, which contains 588 genes relating to tumor biology, was used to screen normal nasopharyngeal tissue, nasopharyngeal cancer (NPC). The reverse transcription/polymerase chain reaction was used to confirm the expression pattern of some genes identified by Atlas hybridization. RESULTS: The differentially expressed cell cycle/growth control regulators in NPC showed a stronger tendency toward cell proliferation with the up-regulation of cyclin D1, cyclin D2 etc. The expression pattern of apoptosis-related genes demonstrated the up-regulation of both anti-apoptotic factors such as the BCL-2-related protein A1, TRAF3, the inhibitor of apoptosis protein A1 (IAPI) and apoptotic pathway elements such as Fas/Apo-1, Apo-2 ligand etc. Among oncogenes/tumor suppressors, MDM2, STAT1 and STAT2 were found to be up-regulated in NPC. The expression profile of growth factors/cytokines showed the up-regulation of many growth-enhancing factors such as EGR1, tumor-derived growth factor 1, platelet-derived growth factor A chain etc. as well as Th1-type cytokines e.g. interleukin-1beta and interferons. A smaller number of genes were down-regulated in nasopharyngeal cancer, such as those encoding ERK1, Raf, secreted apoptosis-related protein 1, CD27BP, transforming growth factor beta2, pre-B-cell-stimulating factor homologue etc. CONCLUSION: The consistent tendency toward cell proliferation, the possibility of a stronger antiapoptotic force that operates on the normal apoptotic pathway, or the autocrine or paracrine growth factors may account for the development of NPC. Some genes are reported for the first time to have changed expression in nasopharyngeal carcinoma. The simple, quick, and high-throughput method of profiling gene expression by cDNA array hybridization provides us with a quick overview of key factors that may be involved in NPC, and may identify genes suitable for further study of carcinogenesis mechanism or targets for possible molecular diagnosis or therapy.

Apoptosis↗

Growth factors in clinical practice.

Growth factors enhance protein synthesis and thus reduce the catabolic response to injury. As a result of bioengineering and new manufacturing techniques several anabolic agents have become available for clinical use and have been evaluated in surgical patients with catabolic illness. Data support the anabolic effects of growth home in such patients, but its expense and possible deleterious effects during the acute phase of illness limit its use to selected patient groups. Insulin-like growth factor-1 has also been studied, but specific indications for its use have not been identified in catabolic patients. Testosterone and derivatives of this hormone exert anabolic effects, but few randomized trials include catabolic surgical patients, and higher doses of some derivative compounds are associated with hepatic dysfunction. Nonetheless, as we move into the future, studies will determine the specific doses for administration of these and other anabolic factors in specific patient groups. Anabolic therapy will shorten the length of therapy and improve the outcome in the future.

Anabolic Agents↗

Innervation of the rat pineal gland by PACAP-immunoreactive nerve fibers originating in the trigeminal ganglion: a degeneration study.

In order to establish that the pineal gland is innervated by pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive nerve fibers originating in the trigeminal ganglion, ophthalmic and maxillary nerves were transected by using a subtemporal fossa approach. The number of PACAP-immunoreactive nerve fibers in the pineal gland of rats with a total transection of the nerve was compared with that of rats without surgery. In the operated rat, PACAP-immunoreactive nerve fibers in the superficial pineal decreased remarkably, indicating that the trigeminal ganglion was the origin of these nerve fibers. This research provides evidence supporting the hypothesis that PACAP-immunoreactive nerves regulate the synthesis and/or secretion of melatonin in the pineal gland.

Animals↗

Determination of the complete nucleotide sequence of a vaccine strain of porcine reproductive and respiratory syndrome virus and identification of the Nsp2 gene with a unique insertion.

The complete nucleotide sequence of the genomic RNA of a vaccine strain (SP) of porcine reproductive and respiratory syndrome virus (PRRSV) was determined. It shares approximately 94% identity of nucleotide sequence with two recently reported North American strains, 16244B and VR2332, but only 78% with a European strain, Lelystad virus (LV). Its genome is the longest among the four published complete sequences of PRRSV, due to an insertion in the Nsp2-encoding region. Compared to Nsp2 of the North American strains and the European strain, the predicted Nsp2 of strain SP contains 36 and 155 amino acid insertions, respectively, near the C-terminus, in addition to several highly variable regions. The insertion shows no homology with any equivalent arterivirus proteins. This high sequence disparity of Nsp2 among different PRRSV isolates suggested that it could be used as a marker to differentiate PRRSV genotypes. The 5' RACE and primer extension analysis of three North American strains demonstrated that the utmost 5'-end nucleotides are conserved among PRRSV strains isolated from two continents. The predicted polyprotein 1 a/b contains conserved proteinase, polymerase and helicase domains responsible for polyprotein processing, RNA transcription and replication.

Animals↗

Are antioxidant levels measured immediately postoperatively an indicator of magnitude of injury?

BACKGROUND: Little is known about the changes that occur in antioxidant levels in response to surgical trauma. The antioxidant system may influence recovery and healing after operation. Miller et al described a reliable assay for total antioxidant capacity of serum. We studied changes in antioxidant levels secondary to operation using this assay. METHODS: Twenty-seven patients were studied: 14 abdominal and 13 breast cancer operations. Initial blood samples were obtained when starting the preoperative intravenous line, the second in the recovery room, and every 6 hours thereafter. RESULTS: Levels did not correlate with diagnosis, extent of operation, age, body mass index, or complications. Differences between preoperative and postoperative values in the down and up groups were significant at P = 0.002 and P = 0.023, respectively. Differences in initial levels between the down and up groups were significant at P = 0.005. Levels 12 hours after operation were stable. CONCLUSIONS: Rapid return to a baseline of approximately 1 micromole/L, regardless of the direction of initial response, supports the concept of a set point for regulation of serum's antioxidant capacity.

Abdomen↗