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Biomedical subjects

Z Guo

Publications and source records attributed to Z Guo.

At least 37 records · Page 2Linked to original sources

The inhibitory effect of VitD3 on proliferation of keratinocyte cell line HACAT is mediated by down-regulation of CXCR2 expression.

Psoriasis is a disease characterized by inflammation and increased population of hyperproliferative keratinocytes. It is well known that chemokines and chemokine receptors, such as interleukin-8 and its receptors (CXCR1 and CXCR2), play important roles in the pathogenesis of psoriasis. So far, examination of CXCR2 expression in psoriatic lesional keratinocytes by FACS calibur has not been reported and whether VitD3 inhibits psoriatic lesional keratinocyte proliferation through down-regulation of CXCR2 expression has not been elucidated. In the present study, CXCR2 expression in psoriatic lesional keratinocytes and HACAT treated with VitD3 was detected by flow cytometry. The proliferative capacity of HACAT treated with VitD3 was assayed by MTT assay. The results showed that CXCR2 expression in psoriatic lesional keratinocytes was higher than that in normal human keratinocytes. At the correct concentration VitD3 could inhibit human keratinocyte proliferation and down-regulate CXCR2 expression in HACAT. The data demonstrate that the inhibitory effect of VitD3 on keratinocyte proliferation might be mediated by down-regulation of CXCR2 expression.

Administration, Topical↗

Overall mass transfer coefficient for pollutant emissions from small water pools under simulated indoor environmental conditions.

Small chamber tests were conducted to experimentally determine the overall mass transfer coefficient for pollutant emissions from still aqueous solutions under simulated indoor (residential or occupational) environmental conditions. The tests covered six organic compounds with a Henry's constant range from 3.33 x 10(-7) to 3.67 x 10(-3) (atm m(3)/mol). The estimated overall liquid phase mass transfer coefficients for still solutions varied from 1.8 x 10(-6) to 5.7 x 10(-3) m/h; the estimated liquid phase mass transfer coefficients were 9.7 x 10(-3) m/h for the reference compound (oxygen) and 5.00 x 10(-3) to 6.04 x 10-(3) m/h for the test compounds. An empirical model is proposed to estimate the overall mass transfer coefficient, which can be used to predict pollutant emissions from still aqueous solutions (e.g. pools and puddles) in indoor environments.

Air Pollution, Indoor↗

Expression of pokeweed antiviral proteins in creeping bentgrass.

Fungal diseases of creeping bentgrass, an important amenity grass used extensively on golf courses, are a serious problem in golf course management. Transgenic approaches to improving disease resistance to fungal diseases are being explored in many species, and in some cases ribosome-inactivating proteins have been found to be effective. We have generated transgenic creeping bentgrass plants expressing three forms of ribosome-inactivating proteins from pokeweed, which are termed pokeweed antiviral proteins (PAP). PAP-Y and PAP-C are nontoxic mutants of PAP; PAPII is the native form of another ribosome-inactivating protein from pokeweed. In creeping bentgrass, PAP-C transformants did not accumulate the protein, suggesting that it is unstable, and in a field test these plants were not protected from infection by the fungal pathogen Sclerotinia homoeocarpa, the causal agent of dollar spot disease. PAPII transformants could accumulate stable levels of the protein but had symptoms of toxicity; one low-expressing line exhibited good disease resistance. PAP-Y transformants accumulated stable levels of protein, and under greenhouse conditions they appeared to be phenotypically normal.

Agrostis↗

Extremely low vertical-emittance beam in the accelerator test facility at KEK.

Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than 1% of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.

Journal Article↗

Effects of long-term enalapril and losartan therapy of heart failure on cardiovascular aldosterone.

Plasma aldosterone escape is found during long-term ACE inhibitor therapy of chronic heart failure. Evidence for aldosterone production in cardiovascular tissues raised the question of whether aldosterone escape occurs or not in these tissues. Rats with infarction-induced chronic heart failure were treated with enalapril (20 mg/kg/d) and losartan (15 mg/kg/d) for 20 weeks. Untreated chronic heart failure and sham-operated rats were used as positive and normal controls, respectively. Ex vivo mesenteric artery and heart perfusion, high performance liquid chromatography, and RIA for aldosterone were performed. Chronic heart failure due to myocardial infarction was associated with tissue-specific activation of cardiovascular aldosterone synthesis. In the mesenteric artery, enalapril significantly inhibited aldosterone production compared to untreated, chronic heart failure rats, and losartan lowered aldosterone production to that of sham rats. In myocardium, enalapril failed to significantly inhibit aldosterone production, and losartan significantly inhibited aldosterone production compared to untreated, chronic heart failure rats. These results provide the first evidence that long-term ACE inhibition therapy induces aldosterone escape in myocardium but not in mesenteric artery of chronic heart failure. The angiotensin II subtype 1 receptor blocker losartan tranquilized aldosterone levels in the cardiovascular tissues of chronic heart failure rats.

Aldosterone↗

Subunit interaction slows the unfolding of the N-terminal domain of creatine kinase in urea.

Fluorescence emission intensity changes with two different excitation wavelengths were used to measure the unfolding rate constants of different domains of muscle type creatine kinase (CK-MM) according to the heterogeneity of aromatic amino acid distributions in the crystal structure of CK-MM. The results were compared with those of brain type creatine kinase (CK-BB) and dithio-bis(succinimidyl propionate) cross-linked CK-MM. CK-BB differed greatly in its distribution of aromatic amino acids in each domain and the unfolding process of cross-linked CK-MM was not accompanied by the dissociation of the dimer. The N-terminal domain of CK-MM was shown to be well protected by subunit interaction during the unfolding of CK-MM in 4 M urea. Dissociating the CK dimer in high urea concentration (> or = 6 M) eliminated the subunit protection. Subunit interactions are also important in preserving secondary structure and forming contracted conformation at low urea concentration.

Circular Dichroism↗

Rapamycin and T cell costimulatory blockade as post-transplant treatment promote fully MHC-mismatched allogeneic bone marrow engraftment under irradiation-free conditioning therapy.

Hematopoietic macrochimerism, established by bone marrow transplantation, can be used as an approach for treating autoimmune disease and inducing transplant tolerance. In this study, we investigated whether a stable, high level of fully MHC-mismatched hematopoietic macrochimerism can be induced by using irradiation-free protocols, and whether rapamycin and T cell costimulatory blockades (anti-CD40L monoclonal antibody (mAb) and CTLA4Ig) as post-transplant treatment promote bone marrow engraftment. Donor-specific blood transfusion (DST), anti-lymphocyte serum (ALS), busulfan, and cyclophosphamide were given pretransplantation. Balb/c (H-2(d)) bone marrow cells, at a dose of 4 x 10(7), were infused into each C57BL/6 mouse (H-2(b)). Rapamycin, anti-CD40L mAb, and CTLA4Ig were then administered, either alone or in combination. Without ALS or busulfan and cyclophosphamide, macrochimerism can only rarely be induced. Donor-specific transfusion (DST) enhances induction of hematopoietic macrochimerism. Rapamycin, anti-CD40L mAb and CTLA4Ig, alone or in combination, induce a stable and high level of hematopoietic macrochimerism. In the chimeric mice, donor-derived cells were detected in all lymphohematopoietic tissues and donor-specific tolerance was induced in vitro. We conclude that a stable and high level of fully MHC-mismatched hematopoietic macrochimerism can be induced in mice after transplanting a single modest dose of bone marrow cells without irradiation. Rapamycin and T cell costimulatory blockade as post-transplant treatment promote bone marrow engraftment.

Animals↗

Genetic parameter estimation for milk yield over multiple parities and various lengths of lactation in Danish Jerseys by random regression models.

The objectives of this study were to test for heterogeneity of genetic and environmental variance among completed and extended records from different lactations or different days in milk (DIM) and to build a model that accounts for this heterogeneity. A total of 147,457 305-d milk yield records from Danish Jersey cows calving between 1984 and early 1999 from two regions of Denmark were used in this study. Results showed that DIM and parity influenced parameters estimated from an animal model with repeated records. Therefore, the data were analyzed using random-regression models that allow the covariance between measurements to change gradually with DIM and parity. Random regressions were fitted for additive genetic effects and permanent environmental effects using second- or third-order normalized Legendre polynomials for DIM and parity. Variances of random-regression coefficients associated with all orders of the polynomials were significant. Based on these parameter estimates, a covariance function (CF) was defined. The CF showed that the heritability decreases over parities, but within each parity heritability increases with DIM, whereas variance of permanent environmental effects increases over parities and decreases with DIM. Generally, genetic correlations were higher between records with similar DIM and parity. The results indicate that there are problems with the extension procedure used to predict 305-d milk yields. Using the covariance functions estimated in this study, breeding values could be predicted that take into account the covariance structure between records from different parities and different DIM.

Analysis of Variance↗

Construction of a square-planar molecular box: self-assembly of palladium(II) complexes of 3,6,9,16,19,22-hexaazatricyclo[22.2.2.2(11,14)]triacon-11,13,24,26(1),27,29-hexaene through hydrogen-bonding interactions.

Binuclear palladium(II) complexes of the macrocyclic polyamine 3,6,9,16,19,22-hexaazatricyclo[22.2.2.2(11,14)]triacon-11,13,24,26(1),2 7,29-hexaene (L) are used to construct molecules having special shapes. In this study two binuclear palladium(II) complexes [Pd(2)LI(2)]I(2)and [Pd(2)LCl(2)](NO(3))(2).H(2)O are synthesized and structurally characterized. X-ray crystallography shows that both complexes exist as one-dimensional chains formed via intermolecular hydrogen-bonding N(3)-H(3C)---X in which X is I and Cl. Moreover, the ligands in both complexes adopt a boatlike conformation that may facilitate the formation of the tetranuclear complex. The cationic aqua complex [Pd(2)L(H(2)O)(m)(NO(3))(n)]((4-n)+, obtained by the treatment of [Pd(2)LI(2)]I(2)and [Pd(2)LCl(2)]Cl(2) with AgNO(3), is used as a building block for the construction of a tetranuclear palladium(II) complex [Pd(4)L(2)(C(2)O(4))(2)](NO(3))(4).6H(2)O. X-ray crystallography shows that the tetranuclear complex forms an open, hydrophobic box. These molecular boxes are connected via the hydrogen bond N(3)-H(3C)---O(4B) (symmetry code B: x, 1 + y, z) into a one-dimensional chain. A two-dimensional structure is formed via pi-pi stacking of the plane defined by C6 to C11 in the one chain and its symmetry-related plane (symmetry code C: -x, -1 - y, 2 - z) in another chain. This study exemplifies a new method for the assembly of molecular boxes using a macrocyclic ligand.

Journal Article↗

Inactivation of the retinoblastoma tumor suppressor induces apoptosis protease-activating factor-1 dependent and independent apoptotic pathways during embryogenesis.

Inactivation of the retinoblastoma (Rb) tumor suppressor in the mouse induces mid-gestational death accompanied by massive apoptosis in certain tissues. Herein, we analyzed the role of the apoptosis protease-activating factor Apaf-1, an essential component of the apoptosome, in mediating apoptosis in Rb-deficient mice. Analysis of compound mutant embryos lacking Rb and Apaf-1 revealed that Apaf-1 was absolutely required for apoptosis in the central nervous system and lens. In contrast, apoptosis in the peripheral nervous system and skeletal muscles only partly depended on Apaf-1 function. The dependency on Apaf-1 coincided with the requirement documented previously for E2F1 and p53 in the respective tissues. Loss of Apaf-1 specifically suppressed apoptosis but not the proliferation and differentiation defects in Rb-mutant embryos. We also show that the Apaf1+ but not the Rb+ allele is retained in pituitary tumors arising in Rb+/-:Apaf1+/- double heterozygous mice. Our results indicate that Apaf-1 plays a critical role in apoptosis in a subset of tissues and that both E2F1:p53:Apaf-1-dependent and -independent apoptotic pathways operate downstream of Rb.

Animals↗

Unprotected oligosaccharides as phase tags: solution-phase synthesis of glycopeptides with solid-phase workups.

[reaction--see text] N-Linked glycopeptides were synthesized from glycosyl asparagines containing unprotected oligosaccharides and other simple amino acids by an Fmoc method. The free oligosaccharide chains were used as phase tags to facilitate the product isolation by a precipitation method. Thus, while the elongation of glycopeptides was achieved in a solution of N-methylpyrrolidinone (NMP), the product of each step could be precipitated by adding ether to the reaction mixtures. The strategy also eliminated the final step of carbohydrate deprotection in glycopeptide synthesis.

Glycopeptides↗

Cutting edge: membrane lymphotoxin regulates CD8(+) T cell-mediated intestinal allograft rejection.

Blocking the CD28/B7 and/or CD154/CD40 costimulatory pathways promotes long-term allograft survival in many transplant models where CD4(+) T cells are necessary for rejection. When CD8(+) T cells are sufficient to mediate rejection, these approaches fail, resulting in costimulation blockade-resistant rejection. To address this problem we examined the role of lymphotoxin-related molecules in CD8(+) T cell-mediated rejection of murine intestinal allografts. Targeting membrane lymphotoxin by means of a fusion protein, mAb, or genetic mutation inhibited rejection of intestinal allografts by CD8(+) T cells. This effect was associated with decreased monokine induced by IFN-gamma (Mig) and secondary lymphoid chemokine (SLC) gene expression within allografts and spleens respectively. Blocking membrane lymphotoxin did not inhibit rejection mediated by CD4(+) T cells. Combining disruption of membrane lymphotoxin and treatment with CTLA4-Ig inhibited rejection in wild-type mice. These data demonstrate that membrane lymphotoxin is an important regulatory molecule for CD8(+) T cells mediating rejection and suggest a strategy to avoid costimulation blockade-resistant rejection.

Abatacept↗

Hydrolysis theory for cisplatin and its analogues based on density functional studies.

Hydrolysis of cisplatin, the most widely used anticancer drug in the world, is believed to be the key activation step before the drug reaching its intracellular target DNA. To obtain an accurate hydrolysis theory for this important class of square-planar Pt(II) complexes, three typical reactions, i.e., the first and second hydrolyses of cisplatin and the hydrolysis of [Pt(dien)Cl](+) (dien = diethylenetriamine), were studied at the experimental temperature with the solvent effect using mPW1PW91/SDD from a comprehensive methodological study on the Hartree-Fock (HF) ab initio method, electron correlation methods, pure density functional theory (DFT) methods, and hybrid HF-DFT methods with several basis sets. The true five stationary states in the second-order nucleophilic substitution (S(N)2) pathway for the hydrolysis process, namely, reactant (R) --> intermediate 1 (I1) --> TS --> intermediate 2 (I2) --> product (P) were obtained and characterized theoretically for the first time. The most remarkable structural variations and the associated atomic charge variations in the hydrolysis process were found to occur in the equatorial plane of the five-coordinate trigonal-bipyramidal (TBP)-like structures of I1, TS, and I2. The reaction with the TS structure of smaller L-M-E angle and more lengthened M-L and M-E bonds was found to have a smaller Gibbs free energy change and accordingly the better hydrolysis yield. It is found that the sum of the three concentric angles in the TBP's equator is near 360 degrees in I1 and I2 and is almost 360 degrees in TS in each reaction. The associated energy profiles again demonstrated a typical S(N)2 reaction curve. The computed forward and backward reaction enthalpy (Delta H(++)) and reaction entropy (Delta S(++)) in the rate-determining step I1 --> TS --> I2 are in good agreement with the experiments. Natural bonding orbital population analysis shows that the charge-separating extent follows the same order of Delta G in studied reactions. Comparing with the computational results of gas-phase reactions, it can be concluded that the solvent effect should be considered to obtain an accurate hydrolysis picture. The most affected structural parameters after solvation are related to the equatorial plane of the TBP-like geometry. The results provide theoretical guidance on detailed understanding on the mechanism of the hydrolysis of cisplatin, which could be useful in the design of novel Pt-based anticancer agents.

Antineoplastic Agents↗

Triglyceride content in skeletal muscle: variability and the source.

Intramyocellular triglycerides (imcTG) of skeletal muscle are an important energy source for muscle work in mammals. However, the metabolism and regulation of this small intracellular neutral lipid pool are largely unknown. This is in part due to the difficulties involved with its sampling and measurement introduced by contaminants of extramyocellular triglycerides (emcTG). The contents of imcTG reported to date for both human and rodent muscle are of unusually high variability not only across species, but also within same individuals and even same muscle groups. Recent studies suggested that the inherent muscle histologic heterogeneity does not appear to be a major source for the high variability as previously believed. Rather, the new experimental data showed that the procedures commonly used to process muscle specimens before lipid extraction appear inadequate to ensure a complete removal of emcTG contaminants. The extramyocellular lipid contaminants cause an overestimation of imcTG content and markedly increase its variability. Careful and meticulous microdissection has been found necessary in order to avoid contamination by emcTG, thereby obtaining pure muscle fibers for extraction of imcTG.

Adipocytes↗

Chromatographic separation of proteins on metal immobilized iminodiacetic acid-bound molded monolithic rods of macroporous poly(glycidyl methacrylate-co-ethylene dimethacrylate).

Continuous rod of macroporous poly(glycidyl methacrylate-co-ethylene dimethacrylate) was prepared by a free radical polymerization within the confines of a stainless-steel column. The epoxide groups of the rod were modified by a reaction with iminodiacetic acid (IDA) that affords the active site to form metal IDA chelates used for immobilized metal affinity chromatography (IMAC). The efficiency of coupling of IDA to the epoxide-contained matrix was studied as a function of reaction time and temperature. High-performance separation of proteins, based on immobilized different metals on the column, were described. The influence of pH on the adsorption capacity of bovine serum albumin on the Cu2+-IDA continuous rod column was investigated in the range from 5.0 to 9.0. Purification of lysozyme from egg white and human serum albumin (HSA) on the commercially available HSA solution were performed on the naked IDA and Cu2+-IDA continuous rod columns, respectively; and the purity of the obtained fractions was detected by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry.

Chromatography, Affinity↗

Discrete-ordinates solution of short-pulsed laser transport in two-dimensional turbid media.

The discrete-ordinates method is formulated to solve transient radiative transfer with the incorporation of a transient term in the transfer equation in two-dimensional rectangular enclosures containing absorbing, emitting, and anisotropically scattering media subject to diffuse and/or collimated laser irradiation. The governing equations resulting from the discrete-ordinates discretization of the angular directions are further discretized in the spatial and the temporal domains by the finite-volume approach. The current formulation is suitable for solving transient laser transport in turbid media as well as for steady-state radiative transfer in many engineering problems. The method is applied to several example problems and compared with existing steady-state solutions and Monte Carlo transient solutions. Good agreement is found in all cases. Short-pulsed laser interaction and propagation in a turbid medium with high scattering albedo are studied. The imaging of an inhomogeneous zone inside a turbid medium is demonstrated.

Journal Article↗