A new inorganic-organic photoluminescent material constructed with helical [Zn(3)(mu3-OH)(mu2-OH)] chains.
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Journal Article↗
Biomedical subjects
J Tao
Publications and source records attributed to J Tao.
Galpha(i2) enhances insulin signaling via suppression of protein-tyrosine phosphatase 1B.
Suppression of the expression of the heterotrimeric G-protein Galpha(i2) in vivo has been shown to provoke insulin resistance, whereas enhanced insulin signaling is observed when Galpha(i2) is overexpressed in vivo. The basis for Galpha(i2) regulation of insulin signaling was explored in transgenic mice with targeted expression of the GTPase-deficient, constitutively active Q205L Galpha(i2) in fat and skeletal muscle. Phosphorylation of insulin receptor and IRS-1 in response to insulin challenge in vivo was markedly amplified in fat and skeletal muscle expressing Q205L Galpha(i2). The expression and activity of the protein-tyrosine phosphatase 1B (PTP1B), but not protein-tyrosine phosphatases SHP-1, SHP-2, and LAR, were constitutively decreased in tissues expressing the Q205L Galpha(i2), providing a direct linkage between insulin signaling and Galpha(i2). The loss of PTP1B expression may explain, in part, the loss of PTP1B activity in the iQ205L transgenic mice. Activation of Galpha(i2) in mouse adipocytes with lysophosphatidic acid was shown to decrease PTP1B activity, whereas pertussis toxin inactivates Galpha(i2), blocks lysophosphatidic acid-stimulated inhibition of PTP1B activity, and blocks tonic suppression of PTP1B activity by Galpha(i2). Elevation of intracellular cAMP in fat cells is shown to increase PTP1B activity, whereas either depression of cAMP levels or direct activation of Galpha(i2) suppresses PTP1B. These data provide the first molecular basis for the interplay between Galpha(i2) and insulin signaling, i.e. activation of Galpha(i2) can suppress both the expression and activity of PTP1B in insulin-sensitive tissues.
Adipose Tissue↗
15-deoxy-Delta 12,14-prostaglandin J2 induces apoptosis of human hepatic myofibroblasts. A pathway involving oxidative stress independently of peroxisome-proliferator-activated receptors.
Hepatic myofibroblasts (hMFs) play a key role in the development of liver fibrosis associated with chronic liver diseases. Apoptosis of these cells is emerging as a key process in the resolution of liver fibrosis. Here, we examined the effects of cyclopentenone prostaglandins on apoptosis of human hMFs. Cyclopentenone prostaglandins of the J series markedly reduced hMF viability, with 15-deoxy-Delta(12,14)-prostaglandin J2 (15-d-PGJ2) being the most potent. This effect was independent of peroxisome-proliferator-activated receptors (PPARs), because PPARgamma and PPARalpha agonists did not affect hMF cell viability, and PPARgamma, the nuclear receptor for 15-d-PGJ2, was not expressed in hMFs. Moreover, 15-d-PGJ2 did not act via a cell surface G protein-coupled receptor, as shown in guanosine-5'-O-(3-thiotriphosphate) binding assays. Cell death resulted from an apoptotic process, because 15-d-PGJ2-treated hMFs exhibited condensed nuclei, fragmented DNA, and elevated caspase-3 activity. Moreover, the caspase inhibitor Z-Val-Ala-Asp(OCH3)-fluoromethyl ketone blocked the cytotoxic effect of 15-d-PGJ2. The apoptotic effects of 15-d-PGJ2 were reproduced by H2O2 and blocked by the antioxidants N-acetylcysteine (NAC), N-(2-mercapto-propionyl)-glycine (NMPG) and pyrrolidine dithiocarbamate (PDTC). Accordingly, 15-d-PGJ2 generated rapid production of reactive oxygen species in hMFs, via a NAC/NMPG/PDTC-sensitive pathway. In conclusion, 15-d-PGJ2 induces apoptosis of human hMFs via a novel mechanism involving oxidative stress and unrelated to activation of its nuclear receptor PPARgamma. These data underline the antifibrogenic potential of 15-d-PGJ2.
Apoptosis↗
Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo.
BACKGROUND: The serine-threonine kinase Akt is activated by several ligand-receptor systems previously shown to be cardioprotective. Akt activation reduces cardiomyocyte apoptosis in models of transient ischemia. Its role in cardiac dysfunction or infarction, however, remains unclear. METHODS AND RESULTS: We examined the effects of a constitutively active Akt mutant (myr-Akt) in a rat model of cardiac ischemia-reperfusion injury. In vivo gene transfer of myr-Akt reduced infarct size by 64% and the number of apoptotic cells by 84% (P<0.005 for each). Ischemia-reperfusion injury decreased regional cardiac wall thickening as well as the maximal rate of left ventricular pressure rise and fall (+dP/dt and -dP/dt). Akt activation restored regional wall thickening and +dP/dt and -dP/dt to levels seen in sham-operated rats. To better understand this benefit, we examined the effects of myr-Akt on hypoxic cardiomyocyte dysfunction in vitro. myr-Akt prevented hypoxia-induced abnormalities in cardiomyocyte calcium transients and shortening. Akt activation also enhanced sarcolemmal expression of Glut-4 in vivo and increased glucose uptake in vitro to the level seen with insulin treatment. CONCLUSIONS: Akt activation exerts a powerful cardioprotective effect after transient ischemia that probably reflects its ability to both inhibit cardiomyocyte death and improve function of surviving cardiomyocytes. Akt may represent an important nodal target for therapy in ischemic and other heart disease.
Adenoviridae↗
Insulin stimulates tyrosine phosphorylation and inactivation of protein-tyrosine phosphatase 1B in vivo.
Protein-tyrosine phosphatase (PTP) 1B has been implicated in negative regulation of insulin action, although little is known of the ability of insulin to regulate PTP1B itself. The ability of insulin to regulate phosphorylation and activation of PTP1B was probed in vivo. Challenge with insulin in vivo provoked a transient, sharp increase in the phosphotyrosine content of PTP1B in fat and skeletal muscle that peaked within 15 min. Insulin stimulated a decline of 60--70% in PTP1B activity. In mouse adipocytes, the inhibition of PTP1B activity and increased tyrosine phosphorylation of the enzyme were blocked by the insulin receptor tyrosine kinase inhibitor AG1024. Phosphoserine content of PTP1B declined in response to insulin stimulation. Elevation of intracellular cyclic AMP provokes a sharp increase in PTP1B activity and leads to increased phosphorylation of serine residues and decreased tyrosine phosphorylation. Suppression of cyclic AMP levels or inhibition of protein kinase A leads to a sharp decline in PTP1B activity, a decrease in phosphoserine content, and an increase in PTP1B phosphotyrosine content. PTP1B appears to be a critical point for insulin and catecholamine counter-regulation.
Adipocytes↗
Pregnancies achieved after transferring frozen morula/compact stage embryos.
OBJECTIVE: To report two cases of frozen embryo transfers in which embryos were frozen at the morula/compact stage and pregnancies were achieved after transfer. DESIGN: Case report. SETTING: Private assisted reproductive program. PATIENT(S): Two women had transfer of embryos that were frozen at the morula/compact stage. INTERVENTION(S): Human morula/compact embryos were cryopreserved and transferred after subsequent thaw. MAIN OUTCOME MEASURE(S): Embryo survival after thawing and subsequent pregnancy outcome. RESULT(S): Three and five compact embryos were frozen on day 4 for two patients, respectively. In the first case, all three embryos survived after thawing, and all were transferred. In the second patient, three of five embryos survived after thawing, and those three surviving embryos were transferred. Pregnancies were achieved in both patients. The first woman became pregnant with twins and delivered two girls weighing 2,270 g and 2,071 g, respectively. The second patient became pregnant with a singleton and delivered a boy weighing 2,837 g. CONCLUSION(S): Human embryos can be frozen and thawed in the morula/compact stage and achieve normal pregnancy. Advantages of embryo freezing/thawing at the morula/compact stage include the following: [1] compared with earlier embryonic stage freezing, morula/compact-stage embryos provide better embryo selection and [2] it is easier and safer to perform assisted hatching on compact-stage embryos when compared with those from other preimplantation stages.
Adult↗
Cryopreservation of mouse embryos at morula/compact stage.
PURPOSE: The objective of this article was to study mouse morula/compact stage embryo postthaw survival rates and postthaw developmental potential. METHODS: Mouse morula/compact stage embryos were classified into 3 substages. Their morphological behavior during the freezing and thawing process were examined. Postthaw survival rates and blastocyst formation rates were compared between the three substages and the pronucleate and the 2-cell stage embryos. Finally, Postthaw fully compacted and late compact embryos were transferred to foster mothers. RESULTS: Blastomeres of early compacting embryos separated from each other during the freezing process, whereas in fully compacted and late compact stages, the blastomeres remain compacted. Fully compacted and late compact stage embryos had higher Postthaw survival rates than other stages, though those were not statistically significant (P > 0.05). These two substages had significantly higher blastocyst formation rates than Postthaw pronucleate and early compacting embryos (P < 0.01). A total of 72 Postthaw fully compacted and late compact embryos were transferred and 20 live offspring were delivered. CONCLUSIONS: After passing early compacting stage, fully compacted and late compact stage mouse embryos have high Postthaw survival rates and significantly higher blastocyst formation rates. Successful cryopreservation of embryos at these two substages has a significant value in embryo selection. The results obtained in this study may provide useful information for human assisted reproductive technology.
Animals↗
Epstein-Barr virus associated polymorphic lymphoproliferative disorders occurring in nontransplant settings.
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Cell Transformation, Viral↗
Isoflurane aggravates the decrease of phosphatidycholine synthesis in alveolar type II cells induced by hydrogen peroxide.
The influence of isoflurane (Iso) on the synthesis and secretion of phosphatidylcholine (PC) of alveolar type II cells (AT II cells) injured by hydrogen peroxide (H2O2) was investigated. After primary culturing for 32 h, AT II cells isolated and purified from adult Sprague-Dawley rats were randomly divided into six groups: control group, 02.8 mM Iso group, 2.8 mM Iso group, 75 microM H2O2 group, 75 microM H2O2 + 0.28 mM Iso group, and 75 microM H202 + 2.8 mM Iso group. Synthesis and secretion of phosphatidylcholine (PC) were detected by 3H-choline chloride incorporation. It was found that 0.28 mM and 2.8 mM Iso significantly reduced PC synthesis compared with the control group (p <0.05, p <0.01, respectively), but not PC secretion. 75 microM H2O2 markedly decreased the synthesis and secretion of PC in AT II cells compared with the control group (p <0.01). 0.28 mM and 2.8 mM Iso aggravated the decrease of PC synthesis induced by H2O2 (p <0.05, p <0.01, respectively), but did not affect PC secretion. These findings suggest that Iso itself may inhibit the synthesis of PC of AT II cells in vitro and further damage the cells' function under peroxidation.
Anesthetics, Inhalation↗
[One stage otoplasty treatment for congenital malformations of the auricle and middle ear].
OBJECTIVE: To investigate the application of one stage otoplasty for congenital atresia of the external acoustic canal and malformations of the middle ear and the auricle. METHOD: Patients with the ear malformations were given surgical reconstruction of one stage otoplasty. The auricle was reconstructed with the rib which was encapsulated with the superthin temporal flap. According to the malformations of the middle ear in patients, I style tympanoplasty and III style tympanoplasty were carried out respectively. All patients were performed myringoplasty with temporal fascia and reconstructed the external acoustic canal with full thickness skin-grafting. RESULT: A long term follow-up (4-6 years) demonstrated that 11 ears were survival of which 8 ears figuration were ideal. The hearing improvement was observed in all patients. CONCLUSION: One stage otoplasty is effective for treatment of the congenital malformations of the external and middle ear.
Adult↗
Structural basis for double-sieve discrimination of L-valine from L-isoleucine and L-threonine by the complex of tRNA(Val) and valyl-tRNA synthetase.
Valyl-tRNA synthetase (ValRS) strictly discriminates the cognate L-valine from the larger L-isoleucine and the isosteric L-threonine by the tRNA-dependent "double sieve" mechanism. In this study, we determined the 2.9 A crystal structure of a complex of Thermus thermophilus ValRS, tRNA(Val), and an analog of the Val-adenylate intermediate. The analog is bound in a pocket, where Pro(41) allows accommodation of the Val and Thr moieties but precludes the Ile moiety (the first sieve), on the aminoacylation domain. The editing domain, which hydrolyzes incorrectly synthesized Thr-tRNA(Val), is bound to the 3' adenosine of tRNA(Val). A contiguous pocket was found to accommodate the Thr moiety, but not the Val moiety (the second sieve). Furthermore, another Thr binding pocket for Thr-adenylate hydrolysis was suggested on the editing domain.
Adenosine↗
Antiproliferative properties of sphingosine 1-phosphate in human hepatic myofibroblasts. A cyclooxygenase-2 mediated pathway.
Proliferation of hepatic myofibroblasts (hMF) is central for the development of fibrosis during liver injury, and factors that may limit their growth are potential antifibrotic agents. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with growth-regulating properties, either via Edg receptors or through intracellular actions. In this study, we examined the effects of S1P on the proliferation of human hMF. Human hMF expressed mRNAs for the S1P receptors Edg1, Edg3, and Edg5. These receptors were functional at nanomolar concentrations and coupled to pertussis toxin-sensitive and -insensitive G proteins, as demonstrated in guanosine 5'-3-O-(thio)triphosphate binding assays. S1P potently inhibited hMF growth (IC(50) = 1 microm), in a pertussis toxin-insensitive manner. Analysis of the mechanisms involved in growth inhibition revealed that S1P rapidly increased prostaglandin E(2) production and in turn cAMP, two growth inhibitory messengers for hMF; C(2)-ceramide and sphingosine, which inhibited hMF proliferation, did not affect cAMP levels. Production of cAMP by S1P was abolished by NS-398, a selective inhibitor of COX-2. Also, S1P potently induced COX-2 protein expression. Blocking COX-2 by NS-398 blunted the antiproliferative effect of S1P. We conclude that S1P inhibits proliferation of hMF, probably via an intracellular mechanism, through early COX-2-dependent release of prostaglandin E(2) and cAMP, and delayed COX-2 induction. Our results shed light on a novel role for S1P as a growth inhibitory mediator and point out its potential involvement in the negative regulation of liver fibrogenesis.
Base Sequence↗
Gene expression networks underlying retinoic acid-induced differentiation of acute promyelocytic leukemia cells.
To elucidate the molecular mechanism of all-trans-retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) cells, the gene expression patterns in the APL cell line NB(4) before and after ATRA treatment were analyzed using complementary DNA array, suppression-subtractive hybridization, and differential-display-polymerase chain reaction. A total of 169 genes, including 8 novel ones, were modulated by ATRA. The ATRA-induced gene expression profiles were in high accord with the differentiation and proliferation status of the NB(4) cells. The time courses of their modulation were interesting. Among the 100 up-regulated genes, the induction of expression occurred most frequently 12-48 hours after ATRA treatment, while 59 of 69 down-regulated genes found their expression suppressed within 8 hours. The transcriptional regulation of 8 induced and 24 repressed genes was not blocked by cycloheximide, which suggests that these genes may be direct targets of the ATRA signaling pathway. A balanced functional network seemed to emerge, and it formed the foundation of decreased cellular proliferation, maintenance of cell viability, increased protein modulation, and promotion of granulocytic maturation. Several cytosolic signaling pathways, including JAKs/STAT and MAPK, may also be implicated in the symphony of differentiation. (Blood. 2000;96:1496-1504)
Antineoplastic Agents↗
Drug target validation: lethal infection blocked by inducible peptide.
Genome projects are generating large numbers of potential new targets for drug discovery. One challenge is target validation, proving the usefulness of a specific target in an animal model. In this paper, we demonstrate a new approach to validation and assay development. We selected in vitro specific peptide binders to a potential pathogen target. By inducing the expression of a selected peptide in pathogen cells causing a lethal infection in mice, the animals were rescued. Thus, by combining in vitro selection methods for peptide binders with inducible expression in animals, the target's validity was rigorously tested and demonstrated. This approach to validation can be generalized and has the potential to become a valuable tool in the drug discovery process.
Amino Acid Sequence↗
Fine-needle aspiration of granulocytic sarcomas: a morphologic and immunophenotypic study of seven cases.
Granulocytic sarcoma is an uncommon extramedullary, solid tumor of myeloid cells. Only rarely has this entity been diagnosed by fine-needle aspiration (FNA) cytology. This report encompasses the cytologic findings of FNAs from seven patients with granulocytic sarcomas, including four male and three female patients with a mean age of 52 years (range, 12 to 77 years). The aspirates were obtained from skin or subcutaneous tissue (four cases), testis (one case), posterior ileum (one case), lymph node (one case), and abdominal washing (one case). Morphology of the aspirates varied from well-differentiated to poorly differentiated cells showing little or no evidence of myeloid differentiation. Thorough search for evidence of myeloid differentiation and a high index of suspicion of granulocytic sarcoma are of paramount importance. In three cases, flow cytometric and immunocytochemical studies were applied to the FNA materials to confirm the myeloid lineage of the cells and the diagnosis. In the other four cases more than one site was involved by the tumor; once the diagnosis of granulocytic sarcoma was established with a biopsy, the FNA sufficed to confirm the diagnosis at another location. This study demonstrates that FNA cytology in conjunction with appropriate immunophenotyping can provide an accurate diagnosis of granulocytic sarcoma. Fine-needle aspiration can reduce the need for surgical intervention when combined with immunophenotypic studies and when additional anatomic sites are involved.
Adolescent↗
A novel (288delC) mutation in exon 2 of GPIIb associated with type I Glanzmann's thrombasthenia.
This work reports the molecular genetic analysis of two patients who suffer mucocutaneous haemorrhages, prolonged bleeding time and failure of platelets to aggregate, either spontaneously or in response to agonists. The absence of platelet surface glycoprotein (GP)IIb-IIIa complexes confirmed the clinical diagnosis of Glanzmann's thrombasthenia (GT). Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis of exon 2 of GPIIb showed polymorphic bands caused by the homozygous deletion of a cytosine at position 288 relative to the translation start site. causing a shifting of the reading frame and appearance of a premature termination codon. The heterozygous relatives showed a reduced platelet content of GPIIb-IIIa, and a correlation was found between the levels of GPIIb mRNA and surface expression of GPIIb-IIIa complexes. Unlike other mRNAs carrying a nonsense mutation, (288Cdel)GPIIb does not force alternative splicing of GPIIb mRNA. As expected, co-transfection of Chinese hamster ovary (CHO) cells with cDNAs encoding GPIIIa and (288delC)GPIIb failed to enhance the surface exposure of GPIIIa. It is concluded that the (288delC)GPIIb mutation is responsible for the thrombasthenic phenotype of the patients. In addition, it has also been determined that heterodimerization of GPIIb-IIIa requires the integrity of exons 2 and 3 of GPIIb.
Adult↗
Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.
Three hundred cDNAs containing putatively entire open reading frames (ORFs) for previously undefined genes were obtained from CD34+ hematopoietic stem/progenitor cells (HSPCs), based on EST cataloging, clone sequencing, in silico cloning, and rapid amplification of cDNA ends (RACE). The cDNA sizes ranged from 360 to 3496 bp and their ORFs coded for peptides of 58-752 amino acids. Public database search indicated that 225 cDNAs exhibited sequence similarities to genes identified across a variety of species. Homology analysis led to the recognition of 50 basic structural motifs/domains among these cDNAs. Genomic exon-intron organization could be established in 243 genes by integration of cDNA data with genome sequence information. Interestingly, a new gene named as HSPC070 on 3p was found to share a sequence of 105bp in 3' UTR with RAF gene in reversed transcription orientation. Chromosomal localizations were obtained using electronic mapping for 192 genes and with radiation hybrid (RH) for 38 genes. Macroarray technique was applied to screen the gene expression patterns in five hematopoietic cell lines (NB4, HL60, U937, K562, and Jurkat) and a number of genes with differential expression were found. The resource work has provided a wide range of information useful not only for expression genomics and annotation of genomic DNA sequence, but also for further research on the function of genes involved in hematopoietic development and differentiation.
Alternative Splicing↗
Absolute and convective instabilities of the natural convection in a vertical heated slot
The spatiotemporal instability of a natural convection flow in vertical heated slot is studied theoretically. The two unstable modes, secondary cell and traveling wave, are illustrated to be absolute and convective instabilities, respectively. Using a model to simulate the temperature gradient in the center of the slot, we propose an interpretation of the mechanism controlling the reverse transition of flow patterns, and explain the temperature fluctuation observed after the reverse transition in terms of the traveling wave mode.
Journal Article↗