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Biomedical subjects

Y Tu

Publications and source records attributed to Y Tu.

At least 37 records · Page 2Linked to original sources
PubMed2001

Active and passive particles: modeling beads in a bacterial bath.

A simple model for the motion of passive particles in a bath of active, self-propelled ones is introduced. It is argued that this approach provides the correct framework within which to cast the recent experimental results obtained by Wu and Libchaber [Phys Rev. Lett. 84, 3017 (2000)] for the diffusive properties of polystyrene beads displaced by bacteria suspended in a two-dimensional fluid film. Our results suggest that superdiffusive behavior should indeed be generically observed in the transition region marking the onset of collective motion.

Bacterial Physiological Phenomena↗
PubMed2001

A new focal adhesion protein that interacts with integrin-linked kinase and regulates cell adhesion and spreading.

Integrin-linked kinase (ILK) is a multidomain focal adhesion (FA) protein that functions as an important regulator of integrin-mediated processes. We report here the identification and characterization of a new calponin homology (CH) domain-containing ILK-binding protein (CH-ILKBP). CH-ILKBP is widely expressed and highly conserved among different organisms from nematodes to human. CH-ILKBP interacts with ILK in vitro and in vivo, and the ILK COOH-terminal domain and the CH-ILKBP CH2 domain mediate the interaction. CH-ILKBP, ILK, and PINCH, a FA protein that binds the NH(2)-terminal domain of ILK, form a complex in cells. Using multiple approaches (epitope-tagged CH-ILKBP, monoclonal anti-CH-ILKBP antibodies, and green fluorescent protein-CH-ILKBP), we demonstrate that CH-ILKBP localizes to FAs and associates with the cytoskeleton. Deletion of the ILK-binding CH2 domain abolished the ability of CH-ILKBP to localize to FAs. Furthermore, the CH2 domain alone is sufficient for FA targeting, and a point mutation that inhibits the ILK-binding impaired the FA localization of CH-ILKBP. Thus, the CH2 domain, through its interaction with ILK, mediates the FA localization of CH-ILKBP. Finally, we show that overexpression of the ILK-binding CH2 fragment or the ILK-binding defective point mutant inhibited cell adhesion and spreading. These findings reveal a novel CH-ILKBP-ILK-PINCH complex and provide important evidence for a crucial role of this complex in the regulation of cell adhesion and cytoskeleton organization.

Actinin↗
PubMed2001

Binding of regulator of G protein signaling (RGS) proteins to phospholipid bilayers. Contribution of location and/or orientation to Gtpase-activating protein activity.

Regulator of G protein signaling (RGS) proteins must bind membranes in an orientation that permits the protein-protein interactions necessary for regulatory activity. RGS4 binds to phospholipid surfaces in a slow, multistep process that leads to maximal GTPase-activating protein (GAP) activity. When RGS4 is added to phospholipid vesicles that contain m2 or m1 muscarinic receptor and G(i), G(z), or G(q), GAP activity increases approximately 3-fold over 4 h at 30 degrees C and more slowly at 20 degrees C. This increase in GAP activity is preceded by several other events that suggest that, after binding, optimal interaction with G protein and receptor requires reorientation of RGS4 on the membrane surface, a conformational change, or both. Binding of RGS4 is initially reversible but becomes irreversible within 5 min. Onset of irreversibility parallels initial quenching of tryptophan fluorescence (t(12) approximately 30 s). Further quenching occurs after binding has become irreversible (t(12) approximately 6 min) but is complete well before maximal GAP activity is attained. These processes all appear to be energetically driven by the amphipathic N-terminal domain of RGS4 and are accelerated by palmitoylation of cysteine residues in this region. The RGS4 N-terminal domain confers similar membrane binding behavior on the RGS domains of either RGS10 or RGSZ1.

Animals↗
PubMed2001

Enantioselective synthesis and stereoselective rearrangements of enol ester epoxides.

Enol esters can be epoxidized with high enantioselectivities using the fructose-derived chiral ketone 1 as catalyst and Oxone as oxidant. A detailed study of enantiomerically enriched enol ester epoxides has revealed that the acid-catalyzed rearrangement can proceed through two distinct pathways, one with retention of configuration and the other with inversion. The competition between the two pathways is highly dependent upon the nature of the acid catalyst. A strong acid favors retention of configuration and a weak acid favors inversion of configuration. Under thermal conditions, these epoxides rearrange highly stereoselectively with inversion of configuration. Either enantiomer of an alpha-acyloxy ketone can be formed from one enantiomer of an enol ester epoxide by judicious choice of reaction conditions.

Catalysis↗
PubMed2001

Identification and kinetic analysis of the interaction between Nck-2 and DOCK180.

Nck-2 is a newly identified adapter protein comprising three N-terminal SH3 domains and one C-terminal SH2 domain. We have identified in a yeast two-hybrid screen DOCK180, a signaling protein implicated in the regulation of membrane ruffling and migration, as a binding protein for Nck-2. Surface plasmon resonance analyses reveal that the second and the third SH3 domains interact with the C-terminal region of DOCK180. The interactions mediated by the individual SH3 domains, however, are much weaker than that of the full length Nck-2. Furthermore, a point mutation that inactivates the second or the third SH3 domain dramatically reduced the interaction of Nck-2 with DOCK180, suggesting that both SH3 domains contribute to the DOCK180 binding. A major Nck-2 binding site, which is recognized primarily by the third SH3 domain, has been mapped to residues 1819-1836 of DOCK180. Two additional, albeit much weaker, Nck-2 SH3 binding sites are located to DOCK180 residues 1793-1810 and 1835-1852 respectively. Consistent with the mutational studies, kinetic analyses by surface plasmon resonance suggest that two binding events with equilibrium dissociation constants of 4.15+/-1.9x10(-7) M and 3.24+/-1.9x10(-9) M mediate the binding of GST-Nck-2 to GST fusion protein containing the C-terminal region of DOCK180. These studies identify a novel interaction between Nck-2 and DOCK180. Furthermore, they provide a detailed analysis of a protein complex formation mediated by multiple SH3 domains revealing that tandem SH3 domains significantly enhance the weak interactions mediated by each individual SH3 domain.

Amino Acid Sequence↗
PubMed2001

Src homology 3 domain-dependent interaction of Nck-2 with insulin receptor substrate-1.

Insulin receptor substrate-1 (IRS-1) is a multi-domain protein that mediates signal transduction from receptors for insulin and other growth factors to a variety of downstream molecules through both tyrosine-phosphorylation-dependent and -independent interactions. While the tyrosine-phosphorylation-dependent interactions mediated by IRS-1 have been well characterized, the molecular basis underlying the tyrosine-phosphorylation-independent IRS-1 interactions is largely unknown. We previously detected, in an in vitro binding assay, interactions of Nck-2 Src homology (SH) 3 domains with IRS-1. We show here that IRS-1 associates with Nck-2 in vivo. Additionally, we have investigated the molecular basis underlying the IRS-1-Nck-2 complex formation. We have found that (i) mutations at the highly conserved tryptophan within the Nck-2 SH3 domains markedly reduced the association with IRS-1, (ii) interactions mediated by multiple SH3 domains enhance the complex formation of Nck-2 with IRS-1, (iii) deletion of either the phosphotyrosine-binding/Shc and IRS-1 NPXY-binding (PTB/SAIN) domains or the Pre-C-terminal domain of IRS-1, but not the pleckstrin homology (PH) domain, reduced the Nck-2 binding, (iv) PTB/SAIN domains or the Pre-C-terminal domain alone is capable of interacting with Nck-2, and (v) the IRS-1-Nck-2 interaction occurs in the absence of other proteins and therefore is direct. These results establish that IRS-1 is a bona fide target of the Nck-2 SH3 domains and reveal that IRS-1 forms a complex with Nck-2 via direct interactions mediated by multiple domains from both binding partners.

Adaptor Proteins, Signal Transducing↗
PubMed2001

A study on the expression of interleukin (IL)-10 and IL-12 P35, P40 mRNA in the psoriatic lesions.

To investigate the possible role of interleukin (IL)-10 and IL-12 in the pathogenesis of psoriatic lesions and to supply theoretical basis for the gene therapy for psoriasis, the expression of IL-10 and IL-12 P35, P40 mRNA in 12 cases of psoriatic lesions and 6 normal skin tissues was detected by using RT-PCR technique. The results showed that the expression of IL-10 mRNA in the psoriatic lesions was significantly lower than that in the normal skin tissues (P < 0.001). The expression of IL-12 P35 was positive both in the psoriatic lesions and in the normal skin tissues. IL-12 P40 mRNA was expressed positively only in the psoriatic lesions but negatively in the normal skin tissues. It was suggested that IL-12 might take an important role in the occurrence and progression of psoriasis, but IL-10 might have certain role in the regression of psoriasis.

Adult↗
PubMed2001

The expression of Fas/FasL in peripheral blood lymphocytes and the level of IL-2 in serum of patients with condyloma acuminata.

In order to investigate the role of the expression of the Fas/FasL in peripheral blood lymphocytes (PBLC) and the level of IL-2 in serum of patients with condyloma acuminata (CA) in the immune pathogenesis of CA, flow cytometry, indirect immunofluorescence labeling and ELISA were performed to detect the expression of the apoptotic regulatory proteins Fas/FasL in PBLC and the level of IL-2 in serum of 60 patients with different course of CA. The results showed that the expression of Fas/FasL in PBLC of the group of short course in CA was significantly higher than that of the normal controls (P < 0.05); the expression of Fas, FasL in PBLC of the group of long course CA was significantly higher than that of the group of short course and the normal controls (P < 0.05 and P < 0.01, respectively); the level of IL-2 in serum of the group of short and long course CA was significantly lower than that of the group of normal controls (P < 0.01); the negative relation was revealed between the expression of Fas/FasL in PBLC and the level of IL-2 in serum of patients with CA (r = -0.76, P < 0.01). It was suggested that the abnormal apoptosis in PBLC and decreased level of IL-2 in serum of CA might play an important role in the course of CA.

Adolescent↗
PubMed2001

BMP-12 gene transfer augmentation of lacerated tendon repair.

Bone morphogenetic protein (BMP) 12 is a recently discovered member of the human BMP family. It is the human homolog of mouse growth/differentiation factor (GDF)-7. Previously we reported that injection of mesenchymal progenitor cells transferred with the BMP-12 gene into the muscles of nude mice induced tendon-like tissue formation. In this study, we further investigated the effect of BMP-12 gene transfer on tendon cells. We observed that adenovirus mediated in vitro BMP-12 gene transfer into chicken tendon cells increased type I collagen synthesis. No change in alkaline phosphatase activity was observed following BMP-12 gene transfer. We also determined that BMP-12 gene transfer into a complete tendon laceration chicken model resulted in a two-fold increase of tensile strength and stiffness of repaired tendons, indicating improved tendon healing in vivo. We conclude that BMP-12 gene transfer is a promising procedure for improving the tendon repair process.

Alkaline Phosphatase↗
PubMed2001

Formation of novel polymeric nanoparticles.

We have found that not only block copolymers but also ionomers can self-assemble in a selective solvent to form surfactant-free nanoparticles. The self-assembly can be induced by chemical reaction, polymer-polymer complexation, and microphase inversion in addition to the temperature. A recently developed microwave method for the preparation of uniform surfactant-free polymeric nanoparticles is also reviewed. Our results have revealed that for a given dispersion, the particle surface area occupied per stabilizer (surfactant, polymer chains, and ionic groups) is close to a constant.

Microspheres↗
PubMed2001

Knowledge of HIV/AIDS transmission and screening in United States blood donors.

BACKGROUND: Increased knowledge of HIV transmission and behavioral and test screening may encourage high-risk blood donors to self-defer. STUDY DESIGN AND METHODS: Knowledge of HIV transmission and screening and the association with demographics, screening test reactivity, and unreported deferrable risks (UDRs) was assessed by a 1998 anonymous mail survey sent to 92,581 blood donors, of whom 57 percent responded. Groups were compared by using weighted chi-square tests and logistic regression analysis. RESULTS: Four percent of the donors thought that it was very likely or somewhat likely for a person to contract HIV from donating blood, and 20 percent perceived a similar risk from blood transfusion. Only 60 percent of the donors knew that the available screening tests may not detect a recent infection. Thirty-seven percent either did not know or felt it was acceptable to donate blood to obtain HIV testing. Those most likely to answer knowledge questions incorrectly were more likely to have a higher prevalence of test reactivity or UDRs and to be <or=25 years old, members of a minority, less educated, non-US-born, or first-time donors. CONCLUSION: Innovative ways to increase donor understanding of the implications of risk behaviors and the limitations of current screening procedures should be developed. They might prevent high-risk individuals from donating blood.

Acquired Immunodeficiency Syndrome↗
PubMed2001

[Clinicopathologic study on chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct].

We studied the clinicopathologic features of 13 cases of chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct (MPD). It occurs frequently in relatively elder men. Diffuse irregular narrowing of the MPD and stenosis of the common bile duct on ERCP, and swelling of the pancreas on US/CT were detected in all cases. An autoimmune mechanism might be involved in the etiology at least in 5 patients with hypergammaglobulinemia and positive autoantibodies. Surgical therapy was performed in 8 patients and 3 patients were treated with steroids. No patients showed recurrence of pancreatitis. Histologic findings were characterized by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis in the pancreas, obliterated phlebitis of the pancreatic veins. Similar inflammatory process involved the bile duct and the gallbladder. These histologic findings were similar to those of multifocal fibrosclerosis. Chronic pancreatitis with diffuse irregular narrowing of the MPD is overlapped with autoimmune pancreatitis in many cases, but may be a variant of multifocal fibrosclerosis involving the pancreas in some cases.

Adult↗
PubMed2001

[Purification of conjugated bilirubin from human urine].

OBJECTIVES: To develop a simple, practical method with fine yield and purity for separating conjugated bilirubin(Bc) from a sustainable and facile material in order that it could serve as a calibrator for total and direct bilirubin determination. METHODS: Isolating Bc from urine of patients with obstructive jaundice by CHCl3: CH3CH2OH(1:1, V/V) followed by CNBr activated Sepharose 4B-HAS affinity chromatography, we analyzed the products by the use of Doumas J-G diazo method and HPLC, respectively. RESULTS: Determined by J-G diazo method, the crude product extracted by CHCl3: CH3CH2OH(1:1, V/V) yields 90.2 +/- 5.4%(n = 3) of urine Bc, the ratio of Bc to total dry weight being 67.9 +/- 6.4%(n = 3). The final product purified by affinity chromatography with the ratio of separation of 1.5, 1.737 and analyzed by HPLC has the yield of 46.9% and purity of 94.7%(BDG of 76.2%, BMG of 18.5%). CONCLUSION: The above data demonstrate that urine conjugated bilirubin can be successfully purified by CHCl3: CH3CH2OH extraction followed by Sephrose-HSA affinity chromatography with sufficient purity and output.

Bilirubin↗
PubMed2001

[Studies on the chemical compound of volatile oils from various species of Citrus grandis].

The volatile oils in Citrus grandis from various species were compared by GC-MS. The results showed that the content of volatile oil from Citrus grandis and Citrus grandis (L.) Osbek var. tomentosa Hort. was from 0.7% to 0.9%. Over 30 chemical compounds were identified from the volatile oils and the types of the compounds were almost the same. But gamma-terpinen could not be identified from Citrus grandis which was rich in Citrus gransis (L.) Osbeck var. tomentosa Hort.

Citrus↗
PubMed2000

The phosphatidylinositol 3-kinase/AKT kinase pathway in multiple myeloma plasma cells: roles in cytokine-dependent survival and proliferative responses.

Interleukin 6 (IL-6) and insulin-like growth factor I (IGF-I) induce proliferative and antiapoptotic responses in multiple myeloma (MM) plasma cells. Because these cytokines may activate the phosphatidylinositol 3-kinase (PI 3-K)/AKT kinase pathway in other cell types, we investigated the role of PI 3-K/AKT in MM cell responses. IGF-I effectively activated PI 3-K in 8226 and OCI-My5 MM cells, but IL-6 was ineffective. However, IL-6 successfully activated PI 3-K in AF-10 MM cells and IL-6-dependent MH.60 plasmacytoma/hybridoma cells. IGF-I also successfully activated PI 3-K in four of four MM patient specimens, and IL-6 activated PI 3-K in three of four specimens. Inhibition of PI 3-K activity with wortmannin or Ly294002 blocked the antiapoptotic effect of IGF-I and the proliferative effect of IL-6 in the myeloma cell lines. Furthermore, a dominant negative PI 3-K construct, expressed in AF-10 cells by adenoviral infection, also significantly inhibited the IL-6 proliferative response in MM cells. In correlation with activation of PI 3-K, IGF-I also effectively activated the AKT kinase in 8226 and OCI-My5 cells, and IL-6 activated AKT in AF-10 and MH.60 cells. However, although incapable of activating PI 3-K in 8226 and OCI-My5 cells, IL-6 successfully activated AKT in these MM lines, suggesting PI 3-K-independent mechanisms of AKT activation. The prevention of a myeloma cell proliferative response resulting from inhibition of PI 3-K activity was not associated with an inhibition of IL-6-dependent extracellular signal-regulated kinase (ERK) activation. These results support a role for the PI 3-K/AKT pathway in cytokine-dependent responses in myeloma cells, which is independent of any activation of the ERK pathway.

Androstadienes↗
PubMed2000

Inhibitory effect of cyclic guanosine 3',5'-monophosphate (cGMP) on the afferent resting activity in the cephalopod statocyst.

The effects of exo- and endogenous cGMP on the resting activity (RA) of afferent crista fibers were studied in isolated preparations of the statocysts of the cuttlefish Sepia officinalis and the squid Sepioteuthis lessoniana. Bath application of the membrane-permeable cGMP analogs 8-bromo-cGMP (B-cGMP) and N(2),2'-o-dibutyryl 3', 5'-cyclic guanosine monophosphate (dB-cGMP), and of the selective inhibitor of cGMP-phosphodiesterase zaprinast (ZAP), caused an inhibition of RA. The inhibitory effects of B-cGMP and dB-cGMP remained when the preparation was pre-treated with: (i) the guanylate cyclase inhibitors 1H-[1,2,4]oxadiazolo[4,3, -a]quinoxalin-1-one (ODQ) or cystamine (CYS); (ii) the adenylate cyclase inhibitors nicotinic acid (NIC-A), 2',3'dideoxyadenosine (DDA), or MDL-12330A (MDL); (iii) the guanylate cyclase inhibitor methylene blue (M-BLU) and the adenylate cyclase inhibitor MDL combined; or (iv) the nitric oxide (NO) synthase inhibitors N(G)-nitric-L-arginine methyl ester HCl (L-NAME) or N(G)-nitro-L-arginine (L-NOARG). These data indicate that cGMP, as an intracellular messenger, has a tonic inhibitory effect on the RA of afferent crista fibers in cephalopod statocysts.

Afferent Pathways↗