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Biomedical subjects

H Shu

Publications and source records attributed to H Shu.

At least 19 recordsLinked to original sources

Analysis of trace amino acid neurotransmitters in hypothalamus of rats after exhausting exercise using microdialysis.

A simple but effective coupling of microdialysis and capillary electrophoresis with laser induced fluorescence detection technique was applied to analysis of amino acid neurotransmitters in the hypothalamus of rats after acute exhausting exercise. The separation of amino acids was achieved using an uncoated fused-silica capillary (57 cm x 75 microm I.D.) with a buffer of 10 mM disodium tetraborate at pH 10 and an applied voltage of 12.5 kV. The detection limit was 10(-10) M for each amino acid. It is sufficiently sensitive and rapid for the determination of amino acids in a 5-microl Microdialysate. In comparison to pre-exercise, a significant increase in the levels of six hypothalamic amino acids (arginine, glycine, lysine, glutamic acid, alanine, gamma-amino-n-butyric acid) was found after exercise. These results demonstrate that the increase of metabolic amino acids in the hypothalamus of rats can be induced by exhausting exercise and suggests that amino acid neurotransmitters may play functional roles in the central effects of exercise.

Amino Acids↗

CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-kappaB activation.

The transcription factor nuclear factor kappaB (NF-kappaB) plays a pivotal role in immune and inflammatory responses. Activation of NF-kappaB requires the activity of IKK, a kinase complex that contains two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit IKKgamma. To understand how IKK activity is regulated, we searched for IKKgamma-interacting proteins by the yeast two-hybrid system. These screenings identified CSN3, a component of the COP9 signalsome, as a protein specifically interacting with IKKgamma. Overexpression of CSN3 inhibits NF-kappaB activation triggered by tumor necrosis factor (TNF), but not interleukin-1 (IL-1). Moreover, overexpression of CSN3 also inhibits NF-kappaB activation triggered by proteins involved in TNF signaling, including TNF-R1, TRAF2, RIP, and NIK, but not by TRAF6, a protein involved in IL-1 signaling. These data suggest that CSN3 is a specific negative regulator of TNF- but not IL-1-induced NF-kappaB activation pathways.

Blotting, Western↗

TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm.

Mammals express four highly conserved TEAD/TEF transcription factors that bind the same DNA sequence, but serve different functions during development. TEAD-2/TEF-4 protein purified from mouse cells was associated predominantly with a novel TEAD-binding domain at the amino terminus of YAP65, a powerful transcriptional coactivator. YAP65 interacted specifically with the carboxyl terminus of all four TEAD proteins. Both this interaction and sequence-specific DNA binding by TEAD were required for transcriptional activation in mouse cells. Expression of YAP in lymphocytic cells that normally do not support TEAD-dependent transcription (e.g., MPC11) resulted in up to 300-fold induction of TEAD activity. Conversely, TEAD overexpression squelched YAP activity. Therefore, the carboxy-terminal acidic activation domain in YAP is the transcriptional activation domain for TEAD transcription factors. However, whereas TEAD was concentrated in the nucleus, excess YAP65 accumulated in the cytoplasm as a complex with the cytoplasmic localization protein, 14-3-3. Because TEAD-dependent transcription was limited by YAP65, and YAP65 also binds Src/Yes protein tyrosine kinases, we propose that YAP65 regulates TEAD-dependent transcription in response to mitogenic signals.

3T3 Cells↗

A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1.

Phosphorylation of the human p53 protein at Ser-392 has been shown to be responsive to UV but not gamma irradiation. Here we describe identification and purification of a mammalian UV-activated protein kinase complex that phosphorylates Ser-392 of p53 in vitro. This kinase complex contains casein kinase 2 (CK2) and the chromatin transcriptional elongation factor FACT (a heterodimer of hSpt16 and SSRP1). In vitro studies show that FACT alters the specificity of CK2 in the complex such that it selectively phosphorylates p53 over other substrates including casein. In addition, phosphorylation by the kinase complex enhances p53 activity. These results thus provide a potential mechanism for p53 activation by UV irradiation.

Amino Acid Sequence↗

Rowed to recovery: the use of phonological and orthographic information in reading Chinese and English.

To examine how readers of Chinese and English take advantage of orthographic and phonological features in reading, the authors investigated the effects of spelling errors on reading text in Chinese and English using the error disruption paradigm of M. Daneman and E. Reingold (1993). Skilled readers in China and the United States read passages in their native language that contained occasional spelling errors. Results showed that under some circumstances very early phonological activation can be identified in English, but no evidence for early phonology was found in Chinese. In both languages, homophone errors showed a benefit in measures of later processing, suggesting that phonology helps readers recover from the disruptive effects of errors. These results suggest that skilled readers take advantage of the special features of particular orthographies but that these orthographic effects may be most pronounced in the early stages of lexical access.

Adult↗

Lexical activation during the recognition of Chinese characters: evidence against early phonological activation.

In two primed-naming experiments involving Chinese character recognition, one with native Mandarin-speaking subjects and another with native Cantonese-speaking subjects, we varied both the stimulus onset asynchrony (SOA) and the prime-target similarity along various lexical dimensions. Across both experiments, the results were as follows: (1) Relatively strong and reliable semantic priming appeared very early across various SOAs, and its onset was not affected by meaning precision, (2) either homophonic priming had negligible effects on target naming or the effects appeared relatively late (only at 57 msec), and (3) graphic inhibition was found across different SOAs. Since the same set of stimuli and procedure were adopted as those in the study of Perfetti and Tan (1998), the present findings raise questions about the reliability and validity of the results from their study that have been used to support the notion that phonology is a constitutive element of character recognition and precedes meaning access in the identification process. Instead, the present results suggest that phonology is optional for accessing meaning in Chinese character recognition among skilled adult readers.

Adult↗

Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity.

A Drosophila homolog of human Down syndrome cell adhesion molecule (DSCAM), an immunoglobulin superfamily member, was isolated by its affinity to Dock, an SH3/SH2 adaptor protein required for axon guidance. Dscam binds directly to both Dock's SH2 and SH3 domains. Genetic studies revealed that Dscam, Dock and Pak, a serine/threonine kinase, act together to direct pathfinding of Bolwig's nerve, containing a subclass of sensory axons, to an intermediate target in the embryo. Dscam also is required for the formation of axon pathways in the embryonic central nervous system. cDNA and genomic analyses reveal the existence of multiple forms of Dscam with a conserved architecture containing variable Ig and transmembrane domains. Alternative splicing can potentially generate more than 38,000 Dscam isoforms. This molecular diversity may contribute to the specificity of neuronal connectivity.

Amino Acid Sequence↗

Activation of PPARalpha or gamma reduces secretion of matrix metalloproteinase 9 but not interleukin 8 from human monocytic THP-1 cells.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that directly control numerous genes of lipid metabolism by binding to response elements in the promoter. It has recently been proposed that PPARgamma may also regulate genes for proinflammatory proteins, not through PPRE binding but by interaction with transcription factors AP-1, STAT, and NF-kappaB. Recent studies with cultured human monocytes, however, have failed to observe an inhibitory effect of PPARgamma agonists on induced expression of TNFalpha and IL-6, genes known to be controlled by AP-1, STAT, and NF-kappaB. In a similar fashion, we show here that PPARalpha (fenofibrate) or PPARgamma (rosiglitazone) agonists failed to modulate LPS-induced secretion of IL-8 in THP-1 cells. When we made parallel observations on another gene, matrix metalloproteinase 9 (MMP-9), we were surprised to find profound downregulation of LPS-induced secretion by both PPARalpha or PPARgamma agonists. These findings suggest that PPAR may regulate only a subset of the proinflammatory genes controlled by AP-1, STAT, and NF-kappaB. Effects of PPARs on MMP-9 may account for the beneficial effect of PPAR agonists in animal models of atherosclerosis.

Cell Nucleus↗

The guanine nucleotide exchange factor trio mediates axonal development in the Drosophila embryo.

Recent analysis of Rho subfamily GTPases in Drosophila revealed roles for Rac and Cdc42 during axonogenesis. Here, we describe the identification and characterization of the Drosophila counterpart of Trio, a guanine nucleotide exchange factor (GEF) that associates with the receptor phosphatase LAR and regulates GTPase activation in vertebrate cells. Mutants deficient in trio activity display defects in both central and peripheral axon pathways reminiscent of phenotypes observed in embryos deficient in small GTPase function. Double mutant analysis shows that trio interacts with Rac in a dose-sensitive manner but not with Rho. Moreover, reduction of trio activity potentiates the phenotype of mutations in the LAR homolog Dlar, suggesting that these proteins collaborate in orchestrating the cytoskeletal events that underlie normal axonogenesis.

Animals↗

Decrease in protein C inhibitor activity and acquired APC resistance during normal pregnancy.

BACKGROUND: Since protein C inhibitor (PCI) inhibits activated protein C (APC) and a number of proteases, one would expect lower concentrations of PCI in a hypercoagulable state due to increased consumption of the inhibitor. Normal pregnancy is associated with a state of activated hemostasis, where response to APC is depressed. We aimed to study whether PCI function varies during normal pregnancy, and assess the relationship between this inhibitor and acquired APC resistance. METHODS: PCI activity in plasma was tested during pregnancy and postpartum in 28 healthy pregnant women without factor V Leiden Arg(506) - Gln mutation and in 14 non-pregnant female controls. The PCI levels determined in the present study was compared to the APC ratio (APC-r), we investigated previously, in the same samples. RESULTS: The levels of PCI in the pregnant group, as compared to that in the control group (4.74 +/- 0.48), gradually decreased from the first to the third trimester, i.e., 3.30 +/- 1.31 microg/mL in week 12 (p < 0.001), 2.66 +/- 1.44 microg/mL in week 20 (p < 0.001), 1.92 +/- 1.18 microg/mL in week 28 (p < 0.001), 1.30 +/- 0.94 microg/mL in week 32 (p < 0.001) and 1.49 +/- 1.12 microg/mL in week 37 (p < 0.001). After delivery, they rose to 5.02 +/- 1.93 microg/mL, similar to that in the controls (p > 0.05). The values of APC-r showed the same tendency during gestation and postpartum. CONCLUSION: With advance of normal pregnancy, decreasing PCI function corresponds to increasing APC resistance, probably due to that activated hemostasis acts as a link connecting the two variables.

Activated Protein C Resistance↗

Ordinal knowledge: number names and number concepts in Chinese and English.

Previous research has demonstrated cross-language variation in early counting associated with linguistic differences in number-naming systems. Ordinal number names are typically learned later than cardinal names, but languages also differ in the regularity with which they form these names. Elementary school children in China and the U.S. showed differences in the acquisition and use of ordinal numbers corresponding to linguistic differences in ordinal names in their native languages. On tasks assessing children's conceptual knowledge of ordinal relations, a more complicated picture emerged. These results suggest that (a) children induce their language's set of ordinal number names by generalization based on rules sanctioned by early examples, and (b) the relation between ordinal names and ordinal concepts is a complex one, with language only one source of difficulty in understanding ordinal relations. Implications for studies of the relation between linguistic structure and cognitive development are discussed, in particular the possibility that effects of linguistic differences may vary for different levels of development and for different aspects of cognition.

Child↗

[Effect of nitrogen on water use efficiency of apple tree].

This paper studied the effect of nitrogen fertilizer on water use efficiency(WUE) and relevant parameters of two years old potted apple trees(Starkrimson/Malus hupenensis) under different soil moisture condition. The results showed that under adequate soil moisture, WUE was decreased with increasing application of nitrogen fertilizer. Nitrogen fertilizer application resulted in an increase of stomatal conductane. Consequently, the transpiration rate was increased more than photosynthetic rate did. Under soil drought, the WUE of plants applied with nitrogen fertilizer was apparently higher than that of control. The WUE value was in the order of high N > medium N > low N. The improvement of WUE was due to the increase of mesophyll capacity, which led to the promotion of photosynthesis.

Malus↗

Optimizing computerized treatment planning for the Gamma Knife by source culling.

PURPOSE: A good plan is crucial to the success of gamma knife treatment, which depends not only on parameters such as the number of shots, shot position, collimator sizes, and shot weight, but also on the number of blocked cobalt sources. However, during treatment, a plug is generally used to block those cobalt sources, so the beam cannot reach critical tissues. We present here an automated method to optimize all of those parameters, and to choose a source set, although the beams of some blocked sources do not hit any critical tissue. This strategy is used to achieve a high dose that better conforms to the tumor shape, and at the same time, avoids healthy tissue. METHODS AND MATERIALS: Using a workstation that integrates the gamma knife treatment planning system, we developed a two-step optimization algorithm. First, we used a modified Powell's method to optimize the location of the shot, collimator size, and shot weight; we used simulated annealing to determine if the number of shots was adequate using this parameter. Then, simulated annealing was used to determine which cobalt sources we needed to block. RESULTS: Application of this optimization method in two cases showed that the treatment plan can be much improved when the set of blocked cobalt sources has been taken into consideration. CONCLUSION: Determining the set of blocked sources is necessary in certain cases. This technique better conforms the desired isodose curves to the outline of the target volume and minimizes damage to the surrounding normal tissues.

Algorithms↗

[Anatomic study and review of the literature on the Martin Gruber anastomosis].

We dissected 72 upper limbs of fresh cadavers and found 17 cases of the Martin-Gruber anastomosis. The incidence was 23.6%. They can be classified into 5 types. Type I (n = 5, 29.4%): Communication between the anterior interosseous and the ulnar nerves. Type II (n = 3, 17.6%): Communication between the median and the ulnar nerves. Type III (n = 3, 17.6%): Communication between the muscular branches of the flexor digitorum profundus muscle (FDP). Type IV (n = 3, 17.6%): Communication between the anterior interosseous and the ulnar nerves, the muscular branches of the flexor digitorum profundus muscle (FDP) originated from the connection. Type V (n = 3, 17.6%): The anastomotic branch originated from the median nerve and joined the ulnar at two different points as well as connecting with the ulnar branch of the FDP. Through histologic examination, we found the number and size of nerve fascicles which every connection contained to be very different. In one case of type II only one single nerve fascicle was found. We propose the hypothesis that the different amounts of nerve fascicles innervate different amounts of intrinsic hand musculature. The communication which contained one single nerve fascicle only innervate the first dorsal interosseous muscle (FDI).

Aged↗

A study on the methods for early serological diagnosis of leprosy and their potential use.

This is a serial study. In this series we have established 12 methods for the early serological diagnosis of leprosy, including the FLA-ABS test, ELISAs with artificial products (ND-O-, ND-P-, NT-O-, NT-P-BSA; PGL-I, whole M. leprae and M. smegmatis), monoclonal antibody specific binding assay (McAb/SBA), latex agglutination test (LAT), and MLPA. These methods were compared with each other on a large scale in leprosy patients and in the field. The results indicate that 1) Excellent results were obtained when ELISAs were conducted with skim milk or egg albumin as the blocking agent and by using blood from earlobes instead of from venipuncture. 2) According to the four "S" standard (sensitivity, specificity, simplicity and speed), among the 12 methods the ND-O-BSA-ELISA (ND-ELISA) is the best and the MLPA is more suitable for use in the field because it is simple and rapid. 3) In the ND-ELISA, the increase or decrease of the OD value has a positive correlation with the BI, and the order of positive rates was a) in various types of leprosy: LL > BL > BB > BT > TT; b) in household contacts (HC), random population (RP), normal controls in endemic areas (ENC) and normal controls in nonendemic areas (NNC): HC > RP > ENC > NNC. 4) In a population with subclinical M. leprae infection, the highest risk group was between the ages of 15 and 25 and had an increase or a persistence of high OD values prior to onset of disease. 5) OD values gradually decreased over time following treatment and these declines paralleled declines in the BI. 6) In cases cured with dapsone therapy, there was an increase or a persistence of high OD values in ND-ELISA prior to the onset of a leprosy relapse. In conclusion, we have compared and evaluated 12 immuno-assays and have shown that the ND-ELISA is the most practical one for use in investigating sero-immunological epidemiology, subclinical infection with M. leprae, early detection of disease, monitoring of antimicrobial therapy, and even for the prediction of leprosy relapse.

Antibodies, Bacterial↗

[Effect of OFQ injection into intracerebroventricular and preoptic area on blood pressure and heart rate in rats].

Orphanin FQ (OFQ) is a novel peptide comprised of an amino acid sequence very similar to that of dynorphin A. In the present investigation the effect of OFQ on cardiovascular activities was studied. Introcerebroventricular (icv) injection of OFQ at doses of 1 and 10 micrograms produced significant decrease in heart rate (HR) and mean arterial pressure (MAP). Icv pretreatment with naloxone could not prevent the hypotensive and bradycardial response produced by 1 microgram OFQ. Injection of 1 microgram OFQ preoptic area (POA) also caused a profound decrease of MAP and HR. These results indicate that OFQ can inhibit cardiovascular activities which are not mediated by mu, delta and kappa receptors. POA may be one of the target areas of these inhibitory effects.

Animals↗

Insulin-like growth factor binding proteins localize to discrete cell culture compartments in periosteal and osteoblast cultures from fetal rat bone.

Insulin-like growth factor (IGF)-I and IGF-II are expressed at biologically effective levels by bone cells. Their stability and activity are modulated by coexpression of IGF binding proteins (IGFBPs). Secreted IGFBPs may partition to soluble, cell-associated, and matrix-bound compartments. Extracellular localization may sequester, store, or present IGFs to appropriate receptors. Of the six IGFBPs known, rat osteoblasts synthesize all but IGFBP-1. Of these, IGFBP-3, -4, and -5 mRNAs are induced by an increase in cAMP. Little is known about extracellular IGFBP localization in bone and nothing about IGFBP expression by nonosteoblastic periosteal bone cells. We compared basal IGFBP expression in periosteal and osteoblast bone cell cultures and assessed the effects of changes in cAMP-dependent protein kinase A or protein kinase C. Basal IGFBP gene expression differed principally in that more IGFBP-2 and -5 occurred in osteoblast cultures, and more IGFBP-3 and -6 occurred in periosteal cultures. An increase in cAMP enhanced IGFBP-3, -4, and -5 mRNAand accordingly increased soluble IGFBP-3, -4, and -5 and matrix-bound IGFBP-3 and -5 in both bone cell populations. In contrast, protein kinase C activators suppressed IGFBP-5 mRNA, and its basal protein levels remained very low. We also detected low Mr bands reactive with antisera to IGFBP-2, -3, and -5, suggesting proteolytic processing or degradation. Our studies reveal that various bone cell populations secrete and bind IGFBPs in selective ways. Importantly, inhibitory IGFBP-4 does not significantly accumulate in cell-associated compartments, even though its secretion is enhanced by cAMP. Because IGFBPs bind IGFs less tightly in cell-bound compartments, they may prolong anabolic effects by agents that increase bone cell cAMP.

Animals↗