[Osteoporosis research: the present and future].
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Aged↗
Biomedical subjects
M Qiu
Publications and source records attributed to M Qiu.
Migration and differentiation of Nkx-2.2+ oligodendrocyte progenitors in embryonic chicken retina.
During early neural development, the Nkx-2.2 homeobox gene is initially induced in the ventral ventricular zone of the central nervous system (CNS). At later stages, Nkx-2.2+ cells migrate away into the surrounding regions and co-express several oligodendrocyte marker genes. Here we report that Nkx-2.2+ cells also migrate into the avian retina from the optic nerve. These Nkx-2.2+ cells are specifically labeled by the early oligodendrocyte markers PDGFR alpha, O4 and GalC, but not the microglial marker QH1 or neuron-specific marker MAP-2. These observations provide further evidence that Nkx-2.2 is selectively expressed in migratory oligodendrocyte progenitor cells and that retina oligodendrocytes originate from the ventral diencephalon.
Animals↗
Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor kinase 1 (HPK1) to activate JNK signaling pathway in T lymphocytes.
Immune cell-specific adaptor proteins create various combinations of multiprotein complexes and integrate signals from cell surface receptors to the nucleus, modulating the specificity and selectivity of intracellular signal transduction. Grap2 is a newly identified adaptor protein specifically expressed in lymphoid tissues. This protein shares 40--50% sequence homology in the SH3 and the SH2 domain with Grb2 and Grap. However, the Grap2 protein has a unique 120-amino acid glutamine- and proline-rich domain between the SH2 and C-terminal SH3 domains. The expression of Grap2 is highly restricted to lymphoid organs and T lymphocytes. In order to understand the role of this specific adaptor protein in immune cell signaling and activation, we searched for the Grap2 interacting protein in T lymphocytes. We found that Grap2 interacted with the hematopoietic progenitor kinase 1 (HPK1) in vitro and in Jurkat T cells. The interaction was mediated by the carboxyl-terminal SH3 domain of Grap2 with the second proline-rich motif of HPK1. Coexpression of Grap2 with HPK1 not only increased the kinase activity of HPK1 in the cell, but also had an additive effect on HPK1 mediated JNK activation. Furthermore, over expression of Grap2 and HPK1 induced significant transcriptional activation of c-Jun in the JNK signaling pathway and IL-2 gene reporter activity in stimulated Jurkat T cells. Therefore, our data suggest that the hematopoietic specific proteins Grap2 and HPK1 form a signaling complex to mediate the c-Jun NH(2)-terminal kinase (JNK) signaling pathway in T cells.
Adaptor Proteins, Signal Transducing↗
Elevated superoxide production by active H-ras enhances human lung WI-38VA-13 cell proliferation, migration and resistance to TNF-alpha.
Accumulating evidence has suggested that cellular production of superoxide acts as an intracellular messenger to regulate gene expression and modulate cellular activities. In this report, we set out to investigate the role of active H-ras-mediated superoxide production on tumor cell malignancy in a SV-40 transformed human lung WI-38 VA-13 cell line. Stable transfection and expression of constitutively active mutant V12-H-ras (V12-H-ras) dramatically increased intracellular production of superoxide. The expression of V12-H-ras significantly enhanced cell proliferation, migration and resistance to TNF-alpha treatment compared to that of parental and vector control cells, while expression of wild type H-ras (WT-H-ras) only had modest effects. Upon scavenging by superoxide dismutase and other molecules that decrease the intracellular level of active H-ras mediated superoxide production, cell proliferation, migration and resistance to TNF-alpha were significantly reduced. Furthermore, we demonstrated that the activation of membrane NADPH oxidase activity by expression of active H-ras contributed to the intracellular superoxide production. The causal relationship between membrane superoxide production and increased cell proliferation, migration, and resistance to TNF-alpha by the expression of active H-ras, has provided direct evidence to demonstrate that superoxide acts as an intracellular messenger to cascade ras oncogenic signal relay and to modulate tumor malignant activity.
Acetophenones↗
Determination of sphinganine, sphingosine and Sa/So ratio in urine of humans exposed to dietary fumonisin B1.
Fumonisin B1 (FB1) is an inhibitor of sphinganine N-acyltransferase and the increase in the sphinganine/ sphingosine (Sa/So) ratio in urine or serum has been proposed as a biomarker to evaluate exposure to fumonisins. The objectives of this study were to (1) develop a liquid chromatographic method sufficiently sensitive to determine the low concentration of free Sa in male human urine, and (2) analyse So and Sa in human urine and monitor the Sa/So ratio in urine of humans exposed to FB1 in corn diets over 1 month. The liquid chromatographic method involved isolation from human urine of exfoliated cells followed by an extraction of free sphingoid bases and their separation and quantification by high performance liquid chromatography. The detection limits for So and Sa were 0.15 ng/ml in female urine (2 ml used) and 0.005 ng/ ml in male urine (60 ml used). Twenty-eight healthy adult volunteers consumed for 1 month a normal diet containing their homegrown corn potentially contaminated with FB1. Immediately preceding the start of the test, morning urine samples for the determination of So and Sa were collected from each person, and the corn samples used in cooking were obtained from each family for the determination of FB1. At the end of the test period, morning-urine samples were collected from each person and analysed again. The daily FB1 intakes were estimated and used to assess the relationship between them and the urinary Sa/So ratios in humans exposed to dietary FB1 over 1 month. All the homegrown corn samples contained FB1 ranging from 0.08 to 41.1 mg/kg, and the estimated daily FB1 intakes ranged from 0.4 to 740 microg/kg b.w./day. The 1-month monitoring results suggest that sphingolipid metabolism of humans could be affected by FB1 intake, the urinary Sa/So ratio may be useful for evaluating FB1 exposure when the contamination of FB1 is high, and that males are more sensitive to FB1 disruption of sphingolipid metabolism than females.
Adult↗
Mice lacking the Nkx6.2 (Gtx) homeodomain transcription factor develop and reproduce normally.
The Nkx homeobox genes are expressed in a variety of developing tissues and have been implicated in controlling tissue patterning and cell differentiation. Expression of Nkx6.2 (Gtx) was previously observed in the embryonic neural tube, testis, and differentiating oligodendrocytes. To investigate the role of Nkx6.2 in the control of cell specification and differentiation, we generated mice with null mutations in Nkx6.2 using the standard gene targeting approach. Null mutant mice were viable and fertile without apparent histological and immunohistochemical changes in the central nervous systems and testis. The absence of detectable phenotypes suggests a redundant function of Nkx6.2 in mouse development.
Animals↗
Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor.
Oligodendrocytes are derived from glial precursors that arise from the ventral neural tube early in development. In the developing chicken CNS, oligodendrocyte progenitors selectively express Nkx2.2 homeodomain transcription factor, raising the possibility that Nkx2.2 may directly regulate oligogliogenesis. In this study, we have examined Nkx2.2 expression in rodent glial precursors and studied the effect of a loss of Nkx2.2 on oligodendrocyte and astrocyte differentiation. We show that Nkx2.2 is also expressed in mammalian oligodendrocyte progenitors and that the differentiation of MBP-positive and PLP-DM20-positive oligodendrocytes is dramatically retarded in Nkx2.2-null mutants along the entire rostrocaudal axis. In contrast, no effect is seen on astrocytic differentiation. Interestingly, absence of Nkx2.2 expression leads to a ventral expansion of the Olig1/Olig2 expression in neuroepithelial cells into the Nkx2.2 domain and a consequent increase in the production of Olig1/Olig2-positive and platelet-derived growth factor receptor alpha-positive oligodendrocyte progenitors. These results strongly suggest that Nkx2.2 regulates the differentiation and/or maturation, but not the initial specification, of oligodendrocyte progenitors. Consistent with this suggestion, overproduction of Nkx2.2 protein in fibroblast cells can induce gene expression from the proteolipid protein promoter.
3T3 Cells↗
[Rapid detection of enterohemorrhagic Escherichia coli in food with multiplex PCR assay].
Rapid detection of enterohemorrhagic Escherichia coli (EHEC) in food was achieved by using multiplex PCR assay. The assay was designed to amplify the 1109, 302 and 228 bp regions of corresponding virulence genes eaeA, hlyAB, slt1 and/or slt2, by using specific primers for each one reaction. In 60 EHEC and other strains, the above three virulence gene sequences were co-amplified from DNA isolated from 12 EHEC O157:H7 strains, 1 O26:H11 strain and 1 O111:H8 strain; eaeA sequence was amplified from DNA isolated from 2 EAEC strains; slt1/2 sequence was amplified from DNA isolated from 1 VTEC strain. No specific amplification product was produced from other 43 non-EHEC strains. For the detection of EHEC in food, results could be obtained within 8 hrs, and the sensitivity of assay was less than or equal to 1.6 cfu/g(ml) of food. The method was applied to 126 food samples, and EHEC was detected in 3 samples.
Animals↗
[Survey on the fumonisins intake and the urinary Sa/So ratio of people suffered from a high incidence of esophageal cancer].
To explore the correlation between fumonisins and human esophageal cancer (HEC), the estimated fumonisin intake and the urinary sphinganine/sphingosine (Sa/So) ratio were investigated in the population with a high HEC incidence in the suburb of Hebi city, Henan province. Fumonisins were detected from 95 percent of corn samples in the endemic area, and the concentration of total fumonisins (fumonisin B1, B2 and B3) was in the range from 7.2 to 726.8 micrograms/kg. The estimated daily intake of fumonisins was in the range from 0 to 4.84 micrograms/(kg.d) in males, while from 0 to 4.04 micrograms/(kg.d) in females. Compared with the population in a low HEC incidence area, Suixian county, Henan province, the urinary Sa/So ratio of males in the endemic area was statistically significant higher, although no difference was observed in females. The results indicated that fumonisin might be one of the risk factors for the occurrence of HEC.
Adult↗
[The effects of quercetin and isorhamnetin on oxidative modification of VLDL induced by Cu2+].
OBJECTIVE: To observe the effects of quercetin(Que) and isorhamnetin (Iso) on the oxidative modification of very low density lipoprotein (VLDL). METHODS: Human VLDL was prepared by one-step ultracentrifuge and oxidized by Cu2+ in vitro; Que and Iso in different concentrations were added to VLDL before incubation with Cu2+. The MDA, vitamin E contents and the activity of superoxide dismutase(SOD) in ox-VLDL were determined. RESULTS: Compared with ox-VLDL group, Que and Iso decreased MDA production in a dependent concentration-manner, Que and Iso also elevated Vit E level and SOD activity markedly. CONCLUSION: This experiment indicates that Que and Iso have similar inhibitory effects on the oxidative modification of VLDL.
Copper↗
GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity.
Regulation of mammalian cell growth and proliferation is governed through receptor-mediated signaling networks that ultimately converge on the cell cycle machinery. Adaptor proteins play essential roles in the formation of intracellular signaling complexes, relaying extracellular signals from the plasma membrane to the nucleus of a cell. The leukocyte-specific adaptor protein Grap2 is a central linker protein in immune cell signaling and activation. Using Grap2 as bait protein, we identified a novel human protein, GCIP (Grap2 cyclin-D interacting protein). We found that GCIP bound to Grap2 in both yeast two-hybrid assays and in mammalian cells through binding to the COOH-terminal unique domain and SH3 domain (designated QC domain) of Grap2. GCIP also associated with cyclin D both in vitro and in vivo. The expression of GCIP was found in all human tissues examined with the highest level of expression in the heart, muscle, peripheral blood leukocytes, and brain. Furthermore, phosphorylation of retinoblastoma protein by cyclin D-dependent protein kinase was reduced and E2F1-mediated transcription activity was inhibited in cells transfected with GCIP. High level expression of GCIP in terminally differentiated tissues and the inhibition of E2F1 transcription activation suggest that GCIP could play an important role in controlling cell differentiation and proliferation.
Adaptor Proteins, Signal Transducing↗
Evidence for the differential regulation of Nkx-6.1 expression in the ventral spinal cord and foregut by Shh-dependent and -independent mechanisms.
The Nkx-6.1 homeodomain transcription factor was previously shown to be expressed in ventral neural progenitor cells and subsequently subsets of unidentified motor neurons during early neural development. In this study, we identify a specific subpopulation of motor neurons, the median half of the lateral motor neuron column (LMCm), that retain a strong expression of Nkx-6.1. In addition, we report novel patterns of Nkx-6.1 expression in several mesenchymal tissues surrounding Sonic hedgehog (Shh)-expressing cells, including ventral spinal meninges, esophageal mesenchyme, and dorsal tracheal mesenchyme. Whereas Shh signaling is required for Nkx-6.1 expression in the ventral neural tube and spinal meninges, an Shh-independent pathway appears to operate in regulating Nkx-6.1 expression in the foregut. The persistent and robust expression of Nkx-6.1 in motor neurons and mesenchymal cells suggests an important role for Nkx-6.1 in controlling cell fate specification and differentiation. genesis 27:6-11, 2000.
Animals↗
Selective expression of Nkx-2.2 transcription factor in chicken oligodendrocyte progenitors and implications for the embryonic origin of oligodendrocytes.
Recent studies have demonstrated that oligodendrocytes originate from the ventral region of the developing spinal cord. However, the precise neuroepithelial origin of oligodendrocytes remains controversial, and the transcriptional control of oligodendrocyte lineage specification is largely unknown. Here we present evidence that oligodendrocytes in the embryonic chicken spinal cord can be generated from neuroepithelial cells that express the Nkx-2.2 homeodomain transcription factor. Nkx-2.2 expression is initially confined to a narrow stripe of neuroepithelium flanking the floor plate. Later, Nkx-2.2+ cells migrate ventrally and dorsolaterally into the surrounding gray and white matter regions where they undergo rapid proliferation. Double labeling experiments revealed that Nkx-2.2+ cells coexpress markers specific for oligodendrocyte progenitors, e.g., PDGFRalpha+, O4, and R-mAb antigens. In the brain, the Nkx-2.2 cells are also highly migratory and can generate oligodendrocytes. The persistent expression of the Nkx-2.2 homeodomain transcription factor in the oligodendrocyte lineage suggests its important role in the control of oligodendrocyte development.
Animals↗
Thermal physiological consideration of precooling procedures in manned space craft.
OBJECTIVE: To explore a space craft precooling temperature at which excessive thermal stress on the crew member could be prevented or reduced in an overheated launch or reentry module. METHOD: Five young male volunteers wearing a space suit participated in 25 tests at sea level. The space suit was either ventilated in a volume air flow rate of 100 L/min (STPD) with ambient air at temperatures (Ta) of 15 degrees C, 10 degrees C, and 5 degrees C, respectively, or not ventilated. Rectal (Tr), mean skin (Tsk) and mean body (Tb) temperatures were measured. RESULT: At Ta 15 degrees C, Tr decreased without significance (from 37.0 +/- 0.2C to 36.7 +/- 0.3 degrees C) in 120-min tests, whereas mean Tsk and mean Tb decreased significantly, and subjects had local cold strain whether the space suit was ventilated or not; while at Ta 10 degrees C, Tr decreased from 37.0 +/- 0.3 degrees C to 36.3 +/- 0.3 degrees C (P < 0.05), subjects had a whole body cold strain, and both mean Tsk and Tb dropped continuously and significantly. CONCLUSION: Ambient temperature 15 degrees C, at which the thermal comfort states of crew was not significantly degraded, was acceptable after precooling in a space craft.
Adolescent↗
[Laparoscopic gastric resection].
OBJECTIVE: To modify laparoscopic surgery for gastric diseases. METHODS: From December 1992 to January 1999, 61 gastric laparoscopic operations were performed in our hospital. The age of the patients ranged from 29 to 78 years (mean 57.4). 17 patients had Billroth II gastrectomy, 1 Billroth I gastrectomy, 2 proximal subtotal gastrectomy, 5 highly selective vagotomy, 3 gastrostomy, and 33 resection of gastric submucosal benign tumor. 54 patients (88.5%) underwent complete laparoscopy, and 7 (11.5%) an assisted one RESULTS: The mean operative time was (164.2 +/- 93.5) min, the mean estimated blood loss was (218.3 +/- 166.6) ml, and the mean hospital stay was (6.8 +/- 2.1) days. Flatus was present within 48 hours in 86% of the patients. Two patients had laparoscopic surgery for early gastric cancer, and were followed up for more than 55 months. Postoperative complication were noted in 2 patients, who were cured by reoperation and endoscopy therapy respectively. Only 4 patients required postoperative analgesics. CONCLUSION: Although specific indications need to be defined, laparoscopic surgery is feasible. But long-term follow-up should be made to evaluate its efficacy in treatment of gastric cancer.
Adult↗
Msx1 is required for the induction of Patched by Sonic hedgehog in the mammalian tooth germ.
We have used the mouse developing tooth germ as a model system to explore the transmission of Sonic hedgehog (Shh) signal in the induction of Patched (Ptc). In the early developing molar tooth germ, Shh is expressed in the dental epithelium, and the transcripts of Shh downstream target genes Ptc and Gli1 are expressed in dental epithelium as well as adjacent mesenchymal tissue. The homeobox gene Msx1 is also expressed in the dental mesenchyme of the molar tooth germ at this time. We show here that the expression of Ptc, but not Gli1, was downregulated in the dental mesenchyme of Msx1 mutants. In wild-type E11.0 molar tooth mesenchyme SHH-soaked beads induced the expression of Ptc and Gli1. However, in Msx1 mutant dental mesenchyme SHH-soaked beads were able to induce Gli1 but failed to induce Ptc expression, indicating a requirement for Msx1 in the induction of Ptc by SHH. Moreover, we show that another signaling molecule, BMP4, was able to induce Ptc expression in wild-type dental mesenchyme, but induced a distinct expression pattern of Ptc in the Msx1 mutant molar mesenchyme. We conclude that in the context of the tooth germ Msx1 is a component of the Shh signaling pathway that leads to Ptc induction. Our results also suggest that the precise pattern of Ptc expression in the prospective tooth-forming region is controlled and coordinated by at least two inductive signaling pathways.
Animals↗
Relationship between ventral stream for object vision and dorsal stream for spatial vision: an fMRI + ERP study.
Recent imaging studies indicated the existence of two visual pathways in humans: a ventral stream for object and form vision and a dorsal stream for spatial and motion vision. The present study was motivated by a stimulating question: Supposing shape and motion are processed separately in the two pathways, how do the respective cortical areas respond to the stimuli of "forms defined by motion"? fMRI and ERP recordings were combined in order to measure the spatiotemporal activation pattern in the two pathways responding to forms defined by motion, which were produced solely by coherent movement of random dots against a background of dynamic or static random dots. The fMRI data indicated that the stimuli of forms defined by motion indeed activated both dorsal MT/V5 and ventral GTi/GF. Furthermore, the RV curves resulting from fMRI-seeded dipole modeling indicated that each pair of dipoles located at MT/V5 or GTi/GF reached the same best-fit point; a single pair of free dipoles located near the fMRI foci of MT/V5 and GTi/GF could be identified at the corresponding best-fit point; and the source waveforms resulting from fixed dipole modeling also showed simultaneous activation of MT/V5 and GTi/GF dipoles in the time interval around the best-fit point. The present results, therefore, suggest that MT/V5 and GTi/GF appear to be activated in parallel and simultaneously responding to forms defined by motion. Such findings raise interesting issues about the hierarchical organization and the functional specialization in the two pathways.
Adult↗
[Advances in the study of mechanism of estrogen in the regulation of bone metabolism].
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Animals↗