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Biomedical subjects

J Wu

Publications and source records attributed to J Wu.

At least 379 records · Page 21Linked to original sources
PubMed2000

MCI-186: further histochemical and biochemical evidence of neuroprotection.

The bioactivity of 3-methyl-1-phenyl-pyrazolin-5-one (MCI-186) was examined based on histochemical changes in drastic global ischemic rat brains. Rats with mean arterial blood pressure reduction were subjected to 60 min cerebral ischemia/80 min reperfusion. Infusion of MCI-186 at 3.0 mg/Kg reduced brain infarction from 21 +/- 4% (saline control, n= 15) to 11 +/- 3% (n=16, p<0.05). By comparison, infusion of up to 20 mg/Kg propyl galalate (PG)--a well documented antioxidant--produced an infarct percentage of 14 +/- 5% (n=8), close to the saline control. Biochemically, the neuroprotective effect of MCI-186 was demonstrated by diminishing the release of creatine kinase (CK) in serum from 3363 +/- 608 U/L (n=14) in saline control to 1989 +/- 293 U/L (n= 15) in MCI group (p<0.05), while PG did not lower the activity of CK significantly. MCI-186 behaves as a free radical scavenger by suppressing the formation of superoxide anion in xanthine oxidase (XO)-hypoxanthine (HP) system (p<0.05). Our data supported our contention that MCI-186 has potent anti-stroke effect with antioxidant activities.

Animals↗
PubMed2000

Comparative Study on the Structure of Water in Reverse Micelles Stabilized with Sodium Bis(2-ethylhexyl) Sulfosuccinate or Sodium Bis(2-ethylhexyl) Phosphate in n-Heptane.

The microstructure of water solubilized in H(2)O/surfactant/n-heptane ternary systems has been investigated by employing (1)H-NMR and FT-IR spectroscopic techniques. Two reverse micellar systems were prepared and studied, i.e., sodium bis(2-ethylhexyl) sulfosuccinate in n-heptane (H(2)O/AOT/n-heptane) and sodium bis(2-ethylhexyl) phosphate in n-heptane (H(2)O/NaDEHP/n-heptane). (1)H-NMR data showed that the chemical shift of water protons for the AOT and NaDEHP reverse micelles varied downfield and upfield, respectively, with an increase of the water content. The opposite shift directions with increasing water content are interpreted as due to a composition change of the solubilized water associated with head-groups and sodium counterions in reverse micellar systems. On the basis of deconvolution results of FT-IR spectra, a four-component model is proposed to interpret the FT-IR and (1)H-NMR results. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Loss of signaling through the G protein, Gz, results in abnormal platelet activation and altered responses to psychoactive drugs.

Heterotrimeric G proteins mediate the earliest step in cell responses to external events by linking cell surface receptors to intracellular signaling pathways. G(z) is a member of the G(i) family of G proteins that is prominently expressed in platelets and brain. Here, we show that deletion of the alpha subunit of G(z) in mice: (i) impairs platelet aggregation by preventing the inhibition of cAMP formation normally seen at physiologic concentrations of epinephrine, and (ii) causes the mice to be more resistant to fatal thromboembolism. Loss of G(zalpha) also results in greatly exaggerated responses to cocaine, reduces the analgesic effects of morphine, and abolishes the effects of widely used antidepressant drugs that act as catecholamine reuptake inhibitors. These changes occur despite the presence of other G(ialpha) family members in the same cells and are not accompanied by detectable compensatory changes in the level of expression of other G protein subunits. Therefore, these results provide insights into receptor selectivity among G proteins and a model for understanding platelet function and the effects of psychoactive drugs.

Animals↗
PubMed2000

Difference in effective dosage of genistein on bone and uterus in ovariectomized mice.

Phytoestrogen including soybean isoflavones has structural similarity to estrogen and exhibits beneficial effects on bone tissue to protect against bone loss under estrogen-deficient conditions. Recent studies also indicate a possible action of isoflavones as endocrine disrupters in reproductive tissues. In this study, we administered various dosages of genistein to ovariectomized (OVX) mice, and compared the effective dosages of genistein on bone and uterus. Treatment with genistein at 0.7 mg/day prevented trabecular bone loss in OVX mice without hypertrophic effects on the uterus, while administration of 5 mg/day of genistein induced uterine hypertrophy. The serum levels of genistein in OVX mice treated with 0.7 mg/day and 5 mg/day were 3-fold (1.3 nmol/ml) and 50-fold (20.4 nmol/ml) higher than that in OVX mice. These results suggest that there is a marked difference between genistein dosages that protect against bone loss and those that induce uterine hypertrophy.

Animals↗
PubMed2000

Phosphate depletion in the western North Atlantic Ocean.

Surface waters of the subtropical Sargasso Sea contain dissolved inorganic phosphate (DIP) concentrations of 0.2 to 1.0 nanomolar, which are sufficiently low to result in phosphorus control of primary production. The DIP concentrations in this area (which receives high inputs of iron-rich dust from arid regions of North Africa) are one to two orders of magnitude lower than surface levels in the North Pacific (where eolian iron inputs are much lower and water column denitrification is much more substantial). These data indicate a severe relative phosphorus depletion in the Atlantic. We hypothesize that nitrogen versus phosphorus limitation of primary production in the present-day ocean may be closely linked to iron supply through control of dinitrogen (N2) fixation, an iron-intensive metabolic process. Although the oceanic phosphorus inventory may set the upper limit for the total amount of organic matter produced in the ocean over geological time scales, at any instant in geological time, oceanic primary production may fall below this limit because of a persistent insufficient iron supply. By controlling N2 fixation, iron may control not only nitrogen versus phosphorus limitation but also carbon fixation and export stoichiometry and hence biological sequestration of atmospheric carbon dioxide.

Atlantic Ocean↗
PubMed2000

Crystal structure of recombinant trypsin-solubilized fragment of cytochrome b(5) and the structural comparison with Val61His mutant.

The crystal structure of the recombinant trypsin-solubilized fragment of the microsomal cytochrome b(5) from bovine liver has been determined at 1.9 A resolution and compared with the reported crystal structure of the lipase-solubilized fragment of the membrane protein cytochrome b(5). The two structures are similar to each other. However, some detailed structural differences are observed: the conformation of the segment Asn16-Ser20 is quite different, some helices around the heme and some segments between the helices are shifted slightly, the heme is rotated about the normal of the mean plane of heme, one of the propionates of the heme exhibits a different conformation. The average coordination distances between the iron and the two nitrogen atoms of the imidazole ligands are the same in the two structures. Most of the structural differences can be attributed to the different intermolecular interactions which result from the crystal packing. The wild-type protein structure is also compared with its Val61His mutant, showing that the heme binding and the main chain conformations are basically identical with each other except for the local area of the mutation site. However, when Val61 is mutated to histidine, the large side chain of His61 is forced to point away from the heme pocket toward the solvent region, disturbing the micro-environment of the heme pocket and influencing the stability and the redox potential of the protein.

Animals↗
PubMed2000

An efficient preparation of vinamidinium hexafluorophosphate salts.

Substituted acetic acids or acetyl chlorides react with phosphorus oxychloride in DMF to yield the vinamidinium salts 3a-j in moderate to excellent recrystallized yields (28-90%). The cations are conveniently isolated as their hexafluorophosphate salts, which are easily handled nonhygroscopic solids. The nitro compound 3l is prepared in 91% yield by nitration of the parent vinamidinium 3k. The X-ray crystal structure is reported for the 2-phenyl isomer 3e and displays minimal overlap of the two pi-systems.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Annulation of ketones with vinamidinium hexafluorophosphate salts: an efficient preparation of trisubstituted pyridines.

alpha-Aryl ketones react with vinamidinium hexafluorophosphate salts to give access to the corresponding 3-arylpyridines. The annulation reactions proceed in good to excellent yields with vinamidinium salts containing electron-withdrawing groups at the beta-position (R(2)). The reaction was applied to the preparation of the COX-2 specific inhibitor 5-chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine (1), as well as a series of analogues.

Cyclooxygenase Inhibitors↗
PubMed2000

Roles of tissue transglutaminase in ethanol-induced inhibition of hepatocyte proliferation and alpha 1-adrenergic signal transduction.

The mechanisms by which ethanol inhibits hepatocyte proliferation have been a source of some considerable investigation. Our studies have suggested a possible role for tissue transglutaminase (tTG) in this process. Others have shown that tTG has two distinctly different functions: it catalyzes protein cross-linking, which can lead to apoptosis and enhancement of extracellular matrix stability, and it can function as a G protein (Galpha(h)). Under that circumstance, we speculated that the cross-linking activity would be decreased and that it would function to enhance hepatocyte proliferation in response to adrenergic stimulation. Ethanol treatment inhibited hepatocyte proliferation and led to enhanced tTG cross-linking activity, whereas treatment of hepatocytes with an alpha1 adrenergic agonist, phenylephrine, enhanced hepatocyte proliferation while decreasing tTG cross-linking. However, phenylephrine treatment of several hepatoma cell lines had no effect on cellular proliferation or tTG cross-linking activity, and of note, Northern blot analysis demonstrated that whereas primary hepatocytes had high levels of the alpha1beta adrenergic receptor (alpha1BAR) mRNA, the hepatoma cell lines did not have this mRNA. When the Hep G(2) cell line was stably transduced with an expression vector containing the alpha1BR cDNA, the cell line responded to phenylephrine treatment with enhanced proliferation and with decreased tTG cross-linking activity. Ethanol treatment of the alpha1BAR-transfected cells suppressed the phospholipase C-mediated signaling pathways, as detected in the phenylephrine-induced Ca(2+) response. These results suggest that phenylephrine stimulation of hepatocyte proliferation appears to be occurring through the alpha1BAR, which is known to be coupled with the tTG G protein moiety, Galpha(h), and that tTG appears to play a significant role in either enhancing or inhibiting hepatocyte proliferation, depending on its cellular location and on whether it functions as a cross-linking enzyme or a G protein.

Animals↗
PubMed2000

Observation of B --> K(+/-) pi(0) and B --> (K)0 pi(0), and evidence for B --> pi(+)pi(-).

We have studied charmless hadronic decays of B mesons into two-body final states with kaons and pions and observe three new processes with the following branching fractions: beta(B-->pi(+)pi(-)) = (4.3(+1. 6)(-1.4)+/-0.5)x10(-6), beta(B-->K(0)pi(0)) = (14.6(+5.9+2.4)(-5.1-3. 3))x10(-6), and beta(B-->K(+)/-pi(0)) = (11.6(+3.0+1.4)(-2.7-1.3))x10(-6). We also update our previous measurements for the decays B-->K(+)/-pi(-/+) and B+/--->K(0)pi(+/-).

Journal Article↗
PubMed2000

Two-body B meson decays to eta and eta('): observation of B --> eta K*.

In a sample of 19 x 10(6) produced B mesons, we have observed the decays B-->eta K(*) and improved our previous measurements of B-->eta'K. The branching fractions we measure for these decay modes are B(B+-->eta K(*+)) = (26.4(+9.6)(-8.2)+/-3.3)x10(-6), B(B(0)-->eta K(*0)) = (13.8(+5.5)(-4.6)+/-1.6)x10(-6), B(B(+)-->eta'K(+) = (80(+10)(-9)+/-7)x10(-6), and B(B(0)-->eta'K0) = (89(+18)(-16)+/-9)x10(-6). We have searched with comparable sensitivity for related decays and report upper limits for these branching fractions.

Journal Article↗
PubMed2000

Measurement of charge asymmetries in charmless hadronic B meson decays.

We search for CP-violating charge asymmetries (alpha(CP)) in the B meson decays to K(+/-)pi(-/+), K(+/-)pi(0), K(0)(S)pi(+/-), K(+/-)eta('), and omega pi(+/-). Using 9.66 million upsilon(4S) decays collected with the CLEO detector, the statistical precision on alpha(CP) is in the range of +/-0.12 to +/-0.25 depending on decay mode. While CP-violating asymmetries of up to +/-0.5 are possible within the standard model, the measured asymmetries are consistent with zero in all five decay modes studied.

Journal Article↗
PubMed2000

Phase-contrast X-ray imaging with a large monolithic X-ray interferometer.

To increase the field of view for large objects in phase-contrast X-ray imaging, a large monolithic X-ray interferometer has been fabricated using an available silicon ingot of diameter 10 cm. A performance study of this interferometer has been carried out using a synchrotron X-ray source. The view size of the interference pattern obtained with this interferometer was 25 mm wide and 15 mm high and its visibility was 79%. Various structures of a sliced human hepatocellular carcinoma were identified as necrosis, hemorrhagic necrosis, normal liver tissue and blood vessel. The performance of this interferometer was sufficient for phase-contrast X-ray imaging.

Journal Article↗
PubMed2000

Fc gamma receptor IIB on follicular dendritic cells regulates the B cell recall response.

Generation of the B cell recall response appears to involve interaction of Ag, in the form of an immune complex (IC) trapped on follicular dendritic cells (FDCs), with germinal center (GC) B cells. Thus, the expression of receptors on FDC and B cells that interact with ICs could be critical to the induction of an optimal recall response. FDCs in GCs, but not in primary follicles, express high levels of the IgG Fc receptor Fc gamma RIIB. This regulated expression of Fc gamma RIIB on FDC and its relation to recall Ab responses were examined both in vitro and in vivo. Trapping of IC in spleen and lymph nodes of Fc gamma RII-/- mice was significantly reduced compared with that in wild-type controls. Addition of ICs to cultures of Ag-specific T and B cells elicited pronounced Ab responses only in the presence of FDCs. However, FDCs derived from Fc gamma RIIB-/- mice supported only low level Ab production in this situation. Similarly, when Fc gamma RIIB-/- mice were transplanted with wild-type Ag-specific T and B cells and challenged with specific Ag, the recall responses were significantly depressed compared with those of controls with wild-type FDC. These results substantiate the hypothesis that FcgammaRIIB expression on FDCs in GCs is important for FDCs to retain ICs and to mediate the conversion of ICs to a highly immunogenic form and for the generation of strong recall responses.

Animals↗
PubMed2000

The pyrido[2,3-d]pyrimidine derivative PD180970 inhibits p210Bcr-Abl tyrosine kinase and induces apoptosis of K562 leukemic cells.

PD180970 is a novel pyrido[2,3-d]pyrimidine class of ATP-competitive inhibitor of protein tyrosine kinases. We found that PD180970 inhibited in vivo tyrosine phosphorylation of p210Bcr-Abl (IC50 = 170 nM) and the p210BcrAbl substrates Gab2 and CrkL (IC50 = 80 nM) in human K562 chronic myelogenous leukemic cells. In vitro, PD180970 potently inhibited autophosphorylation of p210Bcr-Abl (IC50 = 5 nM) and the kinase activity of purified recombinant Abl tyrosine kinase (IC50 = 2.2 nM). Incubation of K562 cells with PD180970 resulted in cell death. Results of nuclear staining, apoptotic-specific poly(ADP-ribose) polymerase cleavage, and annexin V binding assays indicated that PD180970 induced apoptosis of K562 cells. In contrast, PD180970 had no apparent effects on the growth and viability of p210Bcr-Abl-negative HL60 human leukemic cells. Thus, PD180970 is among the most potent inhibitors of the p210Bcr-Abl tyrosine kinase, which is present in almost all cases of human chronic myelogenous leukemia. These findings indicate that PD180970 is a promising candidate as a novel therapeutic agent for Bcr-Abl-positive leukemia.

Annexin A5↗
PubMed2000

Focal adhesion kinase up-regulation and signaling in activated keratinocytes.

BACKGROUND: During wound healing keratinocytes undergo a process called "activation" that enables the cells to spread and migrate on wound matrix molecules. Focal adhesion kinase (FAK) is a key component of integrin-mediated intracellular signaling. We investigated the induction of FAK and its signaling activity during keratinocyte activation. MATERIALS AND METHODS: Keratinocytes were harvested from normal human skin. Previous work has shown that culture of keratinocytes causes activation in a manner similar to reepithelialization. Freshly isolated, unactivated cells were compared with cultured, activated cells. Activated cells were further examined either as growing colonies or after replating on type I collagen. FAK content was assessed by Western blotting. FAK distribution was shown using indirect immunofluorescence. FAK signaling activity was assessed using an antiphosphotyrosine antibody. RESULTS: FAK was not detectable by Western blotting in freshly isolated cells. In contrast FAK was detected in activated cells. FAK was up-regulated between Days 2 and 4 after cell isolation from skin. Immunostaining of activated, growing keratinocyte colonies in vitro showed a diffuse, cytoplasmic pattern. When these cells were replated on collagen, FAK became concentrated in focal adhesions. Lysates from replated cells showed increased tyrosine phosphorylation of FAK. CONCLUSIONS: In summary FAK is induced in keratinocytes in a time course comparable to that of activation. FAK is phosphorylated and undergoes redistribution to focal adhesions when cells are plated on the beta(1) integrin ligand collagen. These data suggest that induction of FAK and subsequent FAK-induced signaling may be responsible for changes in integrin-mediated behavior of activated keratinocytes during reepithelialization.

Cells, Cultured↗
PubMed2000

Requirement of SHP2 binding to Grb2-associated binder-1 for mitogen-activated protein kinase activation in response to lysophosphatidic acid and epidermal growth factor.

Grb2-associated binder-1 (Gab1) is a multisite docking protein containing a pleckstrin homology (PH) domain, multiple potential tyrosine phosphorylation sites, and several proline-rich sequences. Gab1 becomes tyrosine-phosphorylated in cells stimulated with growth factors, cytokines, and ligands for G protein-coupled receptors. A major Gab1-binding protein detected in cells treated with extracellular stimuli is the tyrosine phosphatase, SHP2. Although the role of SHP2-Gab1 interaction in cell signaling has not yet been characterized, SHP2 is known to mediate mitogen-activated protein (MAP) kinase activation induced by the epidermal growth factor (EGF). However, the mechanism by which the SHP2 phosphatase exerts a positive signaling role remains obscure. In this study, we prepared Gab1 mutants lacking the SHP2 binding site (Gab1Y627F), the phosphatidylinositol 3-kinase (PI3K) binding sites (Gab1DeltaPI3K), and the PH domain (Gab1DeltaPH). Expression of Gab1Y627F blocked the extracellular signal-regulated kinase-2 (ERK2) activation by lysophosphatidic acid (LPA) and EGF. Conversely, expression of the wild-type Gab1 in HEK293 cells augmented the LPA receptor Edg2-mediated ERK2 activation. Whereas the PH domain was required for Gab1 mediation of ERK2 activation by LPA, it was not essential for EGF-induced ERK2 activation. Expression of Gab1DeltaPI3K had no apparent effect on ERK2 activation by LPA and EGF in the cells that we have examined. These results establish a role for Gab1 in the LPA-induced MAP kinase pathway and clearly demonstrate that Gab1-SHP2 interaction is essential for ERK2 activation by LPA and EGF. These findings also suggest that the positive role of SHP2 in the MAP kinase pathway depends on its interaction with Gab1.

Animals↗