Advances in cytokine signaling: the role of Jaks and STATs.
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Animals↗
Biomedical subjects
E Chen
Publications and source records attributed to E Chen.
Reliability of the drop test for the lacrimal drainage function.
PURPOSE: The purpose of this study was to investigate the reliability of the drop test. METHODS: The repeatability of the test was studied with the same and three different examiners. The influence of the blink rate was investigated by recording the blink frequency in 63 subjects. The degree of reflex lacrimation during the test was assessed in ten patients. The effect of different test solutions was investigated in ten test subjects. RESULTS: There was no significant difference when the test was repeated either by the same or different examiners. The reflex lacrimation during the drop test was not significant. There was no correlation between drop test result and blink rate. A moderate increase in the viscosity of the test solution affected the lacrimal drainage. CONCLUSION: The drop test is a reliable test for the lacrimal drainage function.
Adolescent↗
Alteration of memory in the reduction of children's distress during repeated aversive medical procedures.
The present study sought to reduce children's distress during aversive medical procedures using a brief, cost-effective intervention aimed at reframing memory. Fifty children diagnosed with leukemia (25 treatment, 25 attention control, aged 3-18) were observed as they underwent 3 consecutive lumbar punctures (LPs; baseline, postintervention, and follow-up). Self-report, physiological, and observable distress measures were collected before and after each LP. At posttreatment, children in the intervention group showed reductions in anticipatory physiological and self-report ratings relative to the control group. At follow-up, these effects generalized to reductions in procedural distress. These results suggest that (a) a simple memory-based intervention is efficacious at reducing children's distress and (b) benefits from this intervention are maintained over 1 week even without continued intervention.
Adaptation, Psychological↗
Blue light induced apoptosis in rat retina.
PURPOSE: To explore cell death in blue light induced retinal damage. METHODS: Sprague-Dawley rats reared under cyclic light were exposed continuously to diffuse blue light (400-480 nm) at 0.64 W/m2 for 3 or 6 h after 22 h of dark adaptation. The rats were kept in darkness and killed immediately, 8, 16 and 24 h following light exposure. The retinal damage by the blue light was examined with a transmission electron microscope. The cell death was characterised by in situ terminal dUTP nick end labelling (TUNEL) and gel electrophoresis. RESULTS: During the 24 h following light exposure, photoreceptor cell death was characterised by progressive condensation and margination of the chromatin, shrinkage or convolution and fragmentation of the nucleus, condensation of the cytoplasm, and formation of apoptotic bodies along with rapid removal of dying cells from damaged areas in the absence of inflammatory response. The TUNEL-positive nuclei were scattered individually in the outer nuclear layer just after light exposure. A wave of massive TUNEL labelling of photoreceptor nuclei peaked at 8-16 h and dropped at 24 h following light exposure. The distribution of TUNEL-positive nuclei was located predominantly at the upper temporal region of the retina, which was the most sensitive area to the damage caused by blue light. Furthermore, the multiples of internucleosomal cleavage of 180-200 base pairs were demonstrated at corresponding time points. CONCLUSION: Photoreceptor cell apoptosis is seen early after the retina is damaged by blue light.
Animals↗
Expression of the mutant thyroid hormone receptor PV in the pituitary of transgenic mice leads to weight reduction.
Resistance to thyroid hormone (RTH) is a genetic disease caused by mutations of the thyroid hormone receptor beta gene (TRbeta). One of the symptoms in some affected individuals is growth retardation. To understand the molecular basis of growth retardation in these patients with RTH, a transgenic mouse was prepared in which the expression of the TRbeta1 mutant PV was targeted to the pituitary using the promoter of the glycoprotein hormone alpha-subunit. The PV mutant was originally identified in a patient with severe growth impairment. The PV mutation is a C-insertion at codon 448 of the TRbeta gene and leads to a frame-shift of the carboxyl-terminal 14 amino acids of TRbeta1, resulting in total loss of triiodothyronine (T3) binding and transcriptional activation. PV was selectively expressed in the pituitary of the transgenic mouse and not in other tissues examined. The transgenic mice showed a significant impairment in weight gain. However, no changes in the serum level of thyroid-stimulating hormone were seen, and no elevation of thyroid hormones was detected in the transgenic mice. The circulating levels of growth hormone and insulin-like growth factor I were not affected in the transgenic mice, suggesting that the growth impairment in RTH is complex and is mediated by pathways that are yet to be elucidated.
Animals↗
Socioeconomic differences in social information processing and cardiovascular reactivity.
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Adolescent↗
Response of glia, mast cells and the blood brain barrier, in transgenic mice expressing interleukin-3 in astrocytes, an experimental model for CNS demyelination.
Transgenic mice overexpressing cytokines facilitate analysis of the effects of these immunomodulators on indigenous cells of the central nervous system. This study examines morphological aspects of demyelination and permeability changes, in a recently described transgenic model (termed GFAP-IL3). GFAP-IL3 mice develop progressive motor disease at approximately 5 months. Lesions identified after disease onset, showed activation of microglia, astroglial proliferation with phagocytosis of lipids, and immigration of macrophages and mast cells into neural parenchyma. Lymphocytes failed to appear until the later stages of the disease. Later, cerebellar and brain stem white matter contained focal demyelinating lesions with intense macrophage infiltration and a proliferative astrocytosis. Dystrophic axonal changes were noted, in addition to demyelination in heavily infiltrated lesions. Mast cells, variably present in the thalamus and meninges of wild type mice, were greatly increased at these sites in GFAP-IL3 mice. Blood-brain barrier (BBB) defects were documented with leakage of intravenously injected horseradish peroxidase. Mast cell infiltration into the CNS and their degranulation at the site of injury, may represent initial events in a spontaneous process of macrophage mediated demyelination in which glial cells and macrophages are both involved in the phagocytic process.
Animals↗
Cyclin E2, a novel G1 cyclin that binds Cdk2 and is aberrantly expressed in human cancers.
A novel cyclin gene was discovered by searching an expressed sequence tag database with a cyclin box profile. The human cyclin E2 gene encodes a 404-amino-acid protein that is most closely related to cyclin E. Cyclin E2 associates with Cdk2 in a functional kinase complex that is inhibited by both p27(Kip1) and p21(Cip1). The catalytic activity associated with cyclin E2 complexes is cell cycle regulated and peaks at the G1/S transition. Overexpression of cyclin E2 in mammalian cells accelerates G1, demonstrating that cyclin E2 may be rate limiting for G1 progression. Unlike cyclin E1, which is expressed in most proliferating normal and tumor cells, cyclin E2 levels were low to undetectable in nontransformed cells and increased significantly in tumor-derived cells. The discovery of a novel second cyclin E family member suggests that multiple unique cyclin E-CDK complexes regulate cell cycle progression.
Amino Acid Sequence↗
[Cost-benefit analysis for hepatitis A vaccine].
OBJECTIVE: To improve economic benefits of hepatitis A (HA) vaccination and to lay a foundation for formulating an immunization strategy for it. METHODS: Health economics methods were used for analyzing the cost-benefit ratio, balance point of cost-benefit and balance point of antibody level after HA vaccination. RESULTS: The benefit-cost ratio (BCR) for HA vaccine was 2.53 in Jiangxing City of Zhejiang Province with an HA-specific incidence rate of 41.15 per ten thousand. Incidence rate of HA was 16.26 per ten thousand at balance point of cost-benefit of HA vaccine. Cost would be reduced if serum HA antibody was screened before vaccination in the population with more than 50% of seropositive HA antibody. CONCLUSION: It indicated that more economic benefits would be gained if mass HA vaccination strategy was used. Vaccinee of choice was those at ages of 15 to 29 years. HA vaccination after antibody screening in the population aged over 25 years would be more economic than the direct use.
Adolescent↗
Comparison of some antineoplastic drugs on inhibiting thrombin catalizing fibrinogen clotting in vitro.
OBJECTIVE: To classify the effect of thrombin, the key enzyme which enables fibrinogen to form fibrin (fibrinogen clotting) on the formation of metastasis by comparing the inhibition of some antineoplastic drugs on fibrinogen clotting in vitro. METHODS: Time intervals of different drugs to reach a maximum OD (340 nm) data in fibrinogen solution added with thrombin were used in this work. RESULTS: It was found that L-4-oxalysine (8-40 micrograms/ml) and arabinosyl cytosine (10-50 micrograms/ml) could inhibit the effect of thrombin by extending the fibrinogen clotting time to 100%-150% (P < 0.001) and 61%-100% (P < 0.001) while the other antimetastatic drugs razoxane, probimane, adriamycin, harringtonine homoharringtonine and alpha-anordrin at the treatment concentrations showed no such activity. The positive rate of drugs to thrombin activity was approximately 25%. CONCLUSION: It suggests that L-4-oxalysine and arabinosyl cytosine may even exhibit antimetastatic effect through thrombin-fibrinogen pathway, and thrombin might operate in tumor metastasis for only limited step but crucial to fibrin formation in tumor nodules.
Amino Acids, Dicarboxylic↗
[Utility of nocturnal oximetry for case finding in patients with suspected sleep apnea syndrome].
OBJECTIVE: Pulse oximeter is a useful screening device for SAS. We studied whether measurement of SaO2 could identify patients with SAS and evaluate the severity of SAS. METHODS: 174 snorers were assessed clinically and then underwent formal PSG and oximetry test at the same time. From the oximetry data, the percentage of time spent at SaO2 below 90% (SIT90%), waking SaO2(H SaO2%), the lowest SaO2(L SaO2%) during sleep, the mean SaO2(M SaO2%) and the number of oxygen desaturation > or = 4% per hour (DI4) were calculated. We also divided 100 cases among them into four groups by AHI, which were G0(AHI < 5), G1(AHI 5-19), G2(AHI 20-39), G3(AHI > or = 40), and evaluated whether the SIT90, ISaO2, MSaO2 and DI4 are different among the four groups. RESULTS: There was an statistically significant correlation (r = 0.91 P < 0.001) between DI4 and AHI. DI4 > or = 5 per hour identified patients with AHI > 5 with a sensitivity of 94%; DI4 > or = 15 per hour identified patients with AHI > 5 with a specificity of 98%, and for patients with AHI > or = 20, the sensitivity was 100%. The SIT90 and DI4 were significantly different among the four groups (P < 0.01). CONCLUSIONS: Oximetry with DI4 < 5 practically excludes clinically significant SAS, and DI4 > or = 15 identified almost all of them. SIT90 and DI4 could be used as parameters in evaluating the severity of SAS.
Circadian Rhythm↗
[The role of breathing control disorder in the development of carbon dioxide retention in patients with obesity hypoventilation syndrome].
OBJECTIVE: To define the role of breathing control in the pathogenesis of carbon dioxide (CO(2)) retention in patients with obesity hypoventilation syndrome. METHODS: 10 obese obstructive sleep apnea syndrome (OSAS) patients were studied. They were separated according to their waking arterial partial pressure of CO(2) (PaCO(2)), 5 being eucapnic and 5 hypercapnic. Both groups had similar body mass index, apnea hypopnea index and normal lung function. The hypoxic (Delta P(0.1)/Delta SaO(2), Delta V(E)/Delta SaO(2)) and the hypercapnic response (Delta P(0.1)/Delta PaCO(2), Delta V(E)/Delta PaCO(2)) were tested before and during continuous positive airway pressure (CPAP) treatment (at 2, 4, 6 weeks). RESULTS: Compared with the eucapnic patients, all the hypercapnic patients had lower Delta P(0.1)/Delta SaO(2) [(-0.04 +/- 0.02) cmH(2)O% vs (-0.14 +/- 0.03) cmH(2)O%], Delta V(E)/Delta SaO(2) [(-0.17 +/- 0.04) L x min(-1)% vs (-0.34 +/- 0.04) L x min(-1)%], Delta P(0.1)/Delta PaCO(2) [(0.23 +/- 0.1) cmH(2)O/mm Hg vs (0.49 +/- 0.1) cmH(2)O/mm Hg], Delta V(E)/Delta PaCO(2) [(1.32 +/- 0.7) L x min(-1) x mm Hg(-1) vs (2.18 +/- 0.81) L x min(-1) x mm Hg(-1)] and the Delta P(0.1)/Delta SaO(2), Delta V(E)/Delta SaO(2) were also lower than the normal value. After treatment with CPAP, the hypercapnic and the hypoxic response of the hypercapnic patients increased gradually, at about 4 approximately 6 week, both of them increased to the normal range, PaCO(2) showed a complete return to eucapnia, their weight were unchanged. CONCLUSION: The depressed breathing control play an important role in the development of CO(2) retention in OSAS patients, and the disorder in breathing control may be secondary to hypoxia, hypercapnia and sleep disorder related to the OSAS.
Adult↗
[Applying combination of ultrasound and CT to diagnose paralaryngeal space tumor].
OBJECTIVE: To explore an effective way to diagnose parapharyngeal space tumor. METHODS: The clinical data of 25 cases of this type of tumor, diagnosed by combinating ultrasound examination and CT scan, were analysed. RESULTS: The diagnosis correspondence rate by the combinating way of ultrasound and CT is 92%. The combination of the two methods is likely able to reveal the overall shape, extend and feature of tumor, and to assist us in decision of the entrance of operation. CONCLUSION: The combination of ultrasound diagaosis and CT scan is of satisfactory clinical value in diagnosis of parapharyngeal space tumor.
Adolescent↗
Glypican 3 and glypican 4 are juxtaposed in Xq26.1.
Recently, we have shown that mutations in the X-linked glypican 3 (GPC3) gene cause the Simpson-Golabi-Behmel overgrowth syndrome (SGBS; ). The next centromeric gene detected is another glypican, glypican 4 (GPC4), with its 5' end 120763bp downstream of the 3' terminus of GPC3. One recovered GPC4 cDNA with an open reading frame of 1668nt encodes a putative protein containing three heparan sulfate glycosylation signals and the 14 signature cysteines of the glypican family. This protein is 94.3% identical to mouse GPC4 and 26% identical to human GPC3. In contrast to GPC3, which produces a single transcript of 2.3kb and is stringently restricted in expression to predominantly mesoderm-derived tissues, Northern analyses show that GPC4 produces two transcripts, 3.4 and 4.6kb, which are very widely expressed (though at a much higher level in fetal lung and kidney). Interestingly, of 20 SGBS patients who showed deletions in GPC3, one was also deleted for part of GPC4. Thus, GPC4 is not required for human viability, even in the absence of GPC3. This patient shows a complex phenotype, including the unusual feature of hydrocephalus; but because an uncle with SGBS is less affected, it remains unclear whether the GPC4 deletion itself contributes to the phenotype.
Abnormalities, Multiple↗
Degradation of proto-oncoprotein c-Rel by the ubiquitin-proteasome pathway.
The c-rel proto-oncogene product, c-Rel, belongs to the Rel/NF-kappaB transcription factor family, which regulates a large variety of cellular functions. The activation of NF-kappaB involves the degradation of the inhibitor, IkappaB, through the ubiquitin-proteasome (Ub-Pr)-mediated pathway. Here we report that the turnover of c-Rel is also regulated by the Ub-Pr pathway, thus adding another level of complexity to the regulation of NF-kappaB. High molecular weight ubiquitinated c-Rel conjugates are detected in cells and accumulate in cells treated with proteasome inhibitors. In a cell-free in vitro degradation assay, c-Rel is degraded specifically through the Ub-Pr pathway. N-terminally truncated c-Rel is readily degraded, implying the dispensability of N-terminal sequence; in contrast, a series of deletion mutants missing C-terminal sequences display a reduced susceptibility to the degradation. Interestingly, the sequence between residues 118 and 171 of c-Rel, i.e. the region immediately following the c-Rel/v-Rel homology domain, appears to play an important role in mediating ubiquitin conjugation and the subsequent degradation. Together with our previous study showing an elevated tumorigenic potential for C-terminally truncated mutants, our data suggest that the C-terminal domain of c-Rel plays an important role in mediating c-Rel degradation and growth control.
3T3 Cells↗
Multiple conformational states of a new hematopoietic cytokine (megakaryocyte growth and development factor): pH- and urea-induced denaturation.
The effect of pH and urea on the conformation of recombinant human megakaryocyte growth and development factor (rHuMGDF) was determined by circular dichroism, intrinsic fluorescence spectroscopy, and equilibrium ultracentrifugation. The conformation of rHuMGDF was dependent on pH and urea concentration. Multiple folding forms were evidenced by multiple pH-induced transitions and urea-induced equilibrium transitions that deviated from a simple two-state process. In neutral to alkaline pH, rHuMGDF exists as a monomer, but an acid-induced conformational state self-associates to form a soluble aggregate. A folding intermediate(s) was observed with a more stable secondary structure than tertiary structure and was dependent on the pH of the urea-induced denaturation. The differences in the stabilities of the folding states were most distinct in the pH range of 4.5 to 6.5. The presence of intermediates in the folding pathway of rHuMGDF are similar to findings of previous studies of related growth factors that share a common three-dimensional structure.
Circular Dichroism↗
Association of Cdk2/cyclin E and NF-kappa B complexes at G1/S phase.
NF-kappa B/Rel family plays a pivotal role in a wide variety of cellular functions including growth, development, apoptosis and stress responses. Recent studies indicated that NF-kappa B is also involved in the cell cycle regulation, and high expression of c-Rel results in a cell cycle arrest at the G1/S-phase transition (Bash, J., Zong, W,-X., and Gelinas, C. (1997) Mol. Cell. Biol. 17, 6526-6536). Here we report the detection of Cdk2, a critical kinase responsible for the G1/S-phase transition, in immune complexes precipitated by the NF-kappa B antisera. Cdk2 and NF-kappa B association was detected by co-precipitation in the nuclear lysates of the G1/S-phase cells, and was found in cultured cell lines and in T cells purified from human peripheral blood. Using an affinity column containing the C-terminal peptide of human c-Rel, we isolated cyclin E, the regulatory subunit of the Cdk2 complex, as a c-Rel-binding protein. These findings support and provide physical basis for the involvement of NF-kappa B in the G1/S-phase cell cycle control, and suggest an important role played by the C-terminal sequence of c-Rel.
Amino Acid Sequence↗
Comparison of upstream regions of X- and Y-chromosomal amelogenin genes.
The amelogenin genes encode abundant enamel proteins that are required for the development of normal tooth enamel. These genes are active only in enamel-forming ameloblasts within the dental organ of the developing tooth, and are part of a small group of genes that are active on both sex chromosomes. The upstream regions of the bovine X- and Y-chromosomal and the sole murine X-chromosomal amelogenin genes have been cloned and sequenced, and conservation at nearly 60% is found in the 300 bp upstream of exon 1 for the 3 genes. A region of the bovine X-chromosomal gene that has inhibitory activity when assayed by gene transfer into heterologous cells includes motifs that have a silencing activity in other genes, and may be important to the mechanism that represses amelogenin expression in non-ameloblast cells in vivo. A comparison of sequences from three genes has led to the identification of several regions with conserved motifs that are strong candidates for having positive or negative regulatory functions, and these regions can now be tested further for interaction with nuclear proteins, and for their ability to regulate expression in vivo.
Amelogenin↗