Biomedical subjects

Z Guo

Publications and source records attributed to Z Guo.

At least 199 records · Page 11Linked to original sources

PubMed1999

Kinetics of formation and stability of [Pt(dien)]2+ complexes with octamer and 14-mer DNA oligonucleotides containing a GG sequence.

Reaction of [Pt(dien)Cl]+ (1) with the 14-mer oligonucleotide 5'-d(ATACATGGTACATA) (I) gave rise to two major species which corresponded to the 5'-G and 3'-G platinated monofunctional adducts, and a minor amount of the bis-platinated adduct formed during the later stages of the reaction. The reaction of (1) with the related octamer 5'-d(ATA-CATGG) (II) was also investigated. Kinetic data obtained by HPLC showed that the 5'-G and 3'-G bases of the 14-mer oligonucleotide were platinated at similar rates: the second-order rate constant is 53 x 10(-2) M-1 s-1 at 298 K in 0.1 M NaClO4. However, the platination rate of 5'-G of the octamer (II) (k = 69 x 10(-2) M-1 s-1) was enhanced by a factor of three compared to the rate of platination at 3'-G (k = 22 x 10(-2) M-1 s-1). All the adducts were separated by HPLC and characterized by NMR spectroscopy, enzymatic digestion and MALDITOF mass spectrometry. 1H and 15N NMR shifts suggest that there are distinct conformational differences between 14-mer duplexes platinated at 5'-G (I5' ds) and 3'-G (I3' ds). Molecular mechanics modelling indicates that rotation around the Pt-N7 bond is more restricted in the case of the 5'-G adduct than in that of the 3'-G adduct. The binding of {Pt(dien)}2+ to 5'-GN7 and 3'-GN7 in the monofunctional adducts of (I) was shown to be reversible upon the addition of high concentrations of chloride ions.

Base Sequence↗

PubMed1999

Effects of cholic acid on blood pressure and production of vascular aldosterone and corticosterone.

The aims of this study were to search for the role of cholic acid in the regulation blood pressure of humans and rats and to investigate the effects of cholic acid on the production of vascular aldosterone and corticosterone in rats. Levels of serum total bile acids were measured by an enzymic spectrophotometeric method in normal controls, patients with essential hypertension, and in Wistar and spontaneously hypertensive rats. Levels in essential hypertension (7.3+/-3.4 micromol/l, n = 88) were higher than those of normal subjects (4.9+/-3.3 micromol/l, n = 86), and levels in SHR (13.9+/-3.8 micromol/l, n = 11) were slightly increased, but not significantly different from Wistar rats (10.4+/-5.1 micromol/l, n = 12). Male Wistar rats received cholic acid 80 mg/kg/day, orally, for 30 days, and blood pressure was monitored by a pressure transducer. Systolic blood pressure increased in Wistar rats treated with cholic acid compared to control rats. Mesenteric artery perfusion ex vivo was performed, and pressor responses to norepinephrine were determined in Wistar rats. The pressor responses to norepinephrine in mesenteric arteries treated with cholic acid were significantly increased. The perfusate from the mesenteric arteries was collected and applied to a Sep-Pak C 18 cartridge column for reverse phase high performance liquid chromatography, and levels of both aldosterone and corticosterone were determined by radioimmunoassay. Levels of aldosterone were decreased but those of corticosterone increased in the perfusate from arteries treated with cholic acid. Reverse transcriptase polymerase chain reaction showed that cholic acid inhibited the expression of 11beta-HSD2 and CYP11B2 mRNA in mesenteric arteries. These results reveal that cholic acid is able to induce hypertension and provide evidence that cholic acid inhibits the transcription of both 11beta-HSD2 and CYP11B2 in vasculature, leading to lower aldosterone and higher corticosterone production in vessels and increased vasoconstrictor responses to norepinephrine.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1999

Protein S-nitrosating agents.

A series of peptidyl N-nitrosoanilines were designed, synthesized, and evaluated as inactivators of cysteine protease papain. These new compounds exhibited different inhibitory activities toward cysteine protease papain in a time- and concentration-dependent manner with second-order rate constants (ki/KI) ranging over two orders of magnitude from 0.604 M-1 sec-1 (1) to 100.36 M-1 sec-1 (7). Formation of the S-NO bond in papain is corroborated by evidence obtained from spectroscopic analyses. The fact that S-nitrosylated enzyme can regain its activity upon addition of thiol compounds such as glutathione makes this class of compounds suitable as templates for the development of potent reversible and covalent cysteine protease inhibitors.

Animals↗

PubMed1999

Review of the assessment of single level and multilevel arterial occlusive disease in lower limbs by duplex ultrasound.

The purpose of this article is to review the performance of duplex ultrasound scanning in assessing lower limb arterial disease with emphasis on patients with multisegmental occlusive lesions. Several studies have reported that duplex scanning can be as accurate as angiography to localize arterial stenoses. In spite of these promising results, there still remain some difficulties and controversies. Among them, it has been reported that multisegmental disease may affect the accuracy of duplex scanning. Indeed, some studies have indicated a lower sensitivity for detecting significant stenoses distal to severe or total occlusions. It also was demonstrated that second-order stenoses were detected with lower sensitivity compared to first-order stenoses. The main reason proposed to explain this lower sensitivity is that the highly reduced flow distal to occluded or highly stenotic segments increases the difficulty of detecting significant Doppler velocity changes in the distal or secondary stenoses. The intrinsic limitations of the peak systolic velocity ratio used as a classification criterion are presented. Finally, new and promising developments in power Doppler imaging and ultrasound contrast agents are discussed, because they may allow expansion of the capabilities of current ultrasound scanning systems and provide more accurate diagnosis of patients with multiple disease.

Arterial Occlusive Diseases↗

PubMed1999

Mortality from dementia in advanced age: a 5-year follow-up study of incident dementia cases.

Five-year follow-up of a community-based, 77+ old cohort including incident dementia cases was used to evaluate the impact of dementia on the risk of death, taking into account other chronic conditions potentially related to death, and contrasting Alzheimer's disease (AD), and vascular dementia (VaD). In this population, 70% of the dementia cases died during the five years after diagnosis, with a mortality rate specific for dementia of 2.4 per 100 person-years. After controlling for sociodemographic variables and comorbidity, 14% of all deaths could be attributed to dementia with a risk of death among demented subjects twice as high as that for non-demented people. Mortality risk ratios were 2.0 (95% confidence interval 1.5-2.7) for AD and 3.3 (95% confidence interval 2.0-5.3) for VaD. This study confirms that dementing disorders are a major risk factor for death. Even in the oldest old (85+), dementia shortens life, especially among women.

Aged↗

PubMed1999

PcaR-mediated activation and repression of pca genes from Pseudomonas putida are propagated by its binding to both the -35 and the -10 promoter elements.

Degradation of protocatechuate in Pseudomonas putida is accomplished by the products of the pca genes (pcaH,G, pcaBDC, pcaI, J and pcaF ). In P. putida, all these genes (with the exception of pcaH,G ) are activated by the regulatory protein PcaR, in association with the pathway intermediate beta-ketoadipate. Having previously cloned and characterized the pcaR locus, we have overexpressed and purified the PcaR protein to homogeneity. The purified PcaR protein was shown to form a homodimer in solution and to bind specifically to its own promoter, as well as to the promoter regions of pcaI, J and pcaF. Subsequent footprint analyses demonstrated that the binding of PcaR to its own promoter occurs within a footprint that extends from the -20 to the +4 position. In contrast, PcaR appeared to interact with the inducible pcaI, J promoter as a dimer of dimers; binding in tandem within a dual footprint encompassing both the '-35' and the '-10' regions of the promoter sequence. The similarities and differences between the two binding patterns correlate well with the very different effects that PcaR has upon transcription at each of the promoter sequences. The interactions at the pcaI, J promoter are reminiscent of those exhibited by the MerR family of regulatory proteins. However, as PcaR bears very little primary sequence homology to any of the regulatory proteins within this family, the results presented here reveal the possible existence of a new series of functionally related transcriptional inducers.

Adipates↗

PubMed1999

Different roles for RhoA during neurite initiation, elongation, and regeneration in PC12 cells.

The goal of the present study was to characterize the effects of RhoA at different stages of nerve growth factor (NGF)-induced neuronal differentiation in the PC12 model. This comparative analysis was prompted by previous studies that reported apparently opposite effects for Rho in different models of neuronal differentiation and regeneration. PC12 cells were transfected with activated V14RhoA or dominant negative N19RhoA under the control of either a constitutive or a steroid-regulated promoter. Upon exposure to NGF, V14RhoA cells continued to proliferate and did not extend neurites; however, they remained responsive to NGF, as indicated by the activation of extracellular signal-regulated kinases. This inability to differentiate was reversed by C3 toxin and activation of cyclic AMP signaling, which inactivate RhoA. N19RhoA expression led to an increase in neurite initiation and branching. In contrast, when the RhoA mutants were expressed after NGF priming, only the rate of neurite extension was altered; V14RhoA clones had neurites approximately twice as long, whereas neurites of N19RhoA cells were approximately 50% shorter than those of appropriate controls. The effects of Rho in neurite regeneration mimicked those observed during the initial stages of morphogenesis; activation inhibited, whereas inactivation promoted, neurite outgrowth. Our results indicate that RhoA function changes at different stages of NGF-induced neuronal differentiation and neurite regeneration.

Animals↗

PubMed1999

Comparison of long-term survival of cytomegalovirus promotre versus Rous Sarcoma virus promoter-driven thymidine kinase gene therapy in nude mice bearing human ovarian cancer.

The cytomegalovirus (CMV) promoter is considered one of the strongest positive regulators leading to expression of higher levels of the thymidine kinase (TK) enzyme than the Rous Sarcoma virus (RSV) promoter in vitro and in vivo. Cell killing efficacy of adenovirus-mediated CMV promoter-driven herpes simplex virus (HSV) TK gene therapy has been found to be 2 to 10 times more effective than RSV driven HSV-TK gene therapy in vitro. In this study the impact of CMV- versus RSV-driven HSV-TK gene therapy on long-term survival of nude mice bearing human ovarian cancer has been evaluated using a prospective randomized experimental design. The experiment was designed to show significance of survival differences from a 50% increase of survived days at a p-value of 0.05 with a power of 80%. All treatment groups showed an increase in median survival compared with control groups. Treatment benefit was ADV/CMV-TK vector dose dependent. At a given viral dose, no significant prolongation of survival was observed comparing CMV- and RSV-driven ADV-TK indicating that simply increasing cell killing efficacy in vitro above a minimal threshold level using a stronger promoter may not lead to prolongation of survival in the HSV-TK/GCV system.

Adenoviridae↗

PubMed1999

Testosterone signaling through internalizable surface receptors in androgen receptor-free macrophages.

Testosterone acts on cells through intracellular transcription-regulating androgen receptors (ARs). Here, we show that mouse IC-21 macrophages lack the classical AR yet exhibit specific nongenomic responses to testosterone. These manifest themselves as testosterone-induced rapid increase in intracellular free [Ca(2+)], which is due to release of Ca(2+) from intracellular Ca(2+) stores. This Ca(2+) mobilization is also inducible by plasma membrane-impermeable testosterone-BSA. It is not affected by the AR blockers cyproterone and flutamide, whereas it is completely inhibited by the phospholipase C inhibitor U-73122 and pertussis toxin. Binding sites for testosterone are detectable on the surface of intact IC-21 cells, which become selectively internalized independent on caveolae and clathrin-coated vesicles upon agonist stimulation. Internalization is dependent on temperature, ATP, cytoskeletal elements, phospholipase C, and G-proteins. Collectively, our data provide evidence for the existence of G-protein-coupled, agonist-sequestrable receptors for testosterone in plasma membranes, which initiate a transcription-independent signaling pathway of testosterone.

Androgen Antagonists↗

PubMed1999

Secretion of phospholipid transfer protein by human hepatoma cell line, Hep G2, is enhanced by sodium butyrate.

Hep G2 cells were used to study the synthesis and secretion of phospholipid transfer protein (PLTP). Upon incubation of the cells at confluence with serum-free Dulbecco's modified Eagle's medium (DMEM), phosphatidylcholine (PC) transfer activity was found to accumulate in the culture media. The PC transfer activity in the media was effectively inhibited by rabbit anti-human PLTP immunoglobulin (Ig)G, thus indicating that the PC transfer activity was due to secreted PLTP. The molecular weight of Hep G2 PLTP was approximately 78 kDa by Western blot analysis, in agreement with the molecular weight obtained for purified human plasma PLTP. The PLTP secreted by Hep G2 also possessed an HDL conversion activity similar to that of human plasma PLTP. The addition of butyrate to the cell culture media resulted in a marked increase in the secretion of PLTP. After 24 h incubation with 4 mmol/L sodium butyrate, a more than twofold increase (P < 0.01) of PC transfer activity in the cell-conditioned media was obtained. The dose-dependent increase in the PC transfer activity in the media upon butyrate treatment was well correlated (r = 0.80, P < 0.01) with that of PLTP mass as determined by immuno-slot blot analysis of cell-conditioned media. The increased secretion of PLTP by Hep G2 treated with sodium butyrate was accompanied by a greater increase in the level of PLTP mRNA in the cells as determined by ribonuclease protection assay. In the presence of 4 mmol/L sodium butyrate, a fourfold increase (P < 0. 01) in mRNA level was obtained at 24 h. No stabilizing effect of butyrate on PLTP mRNA was apparent upon treatment of the cultured cells with the RNA synthesis inhibitor, actinomycin D. Thus, the up-regulatory effect of butyrate on PLTP gene expression seemed to have occurred at the transcriptional level.

Animals↗

PubMed1999

Low blood pressure and incidence of dementia in a very old sample: dependent on initial cognition.

OBJECTIVE: To examine whether initially low blood pressure is related to the incidence of dementia. DESIGN: A population-based prospective study. SETTING: The Kungsholmen district of Stockholm, Sweden PARTICIPANTS: Three hundred four nondemented subjects aged 75 to 96 years at baseline. MEASUREMENTS AND MAIN RESULTS: After an average of 3 years, 81 dementia cases were identified (67 with Alzheimer's disease cases). Compared with individuals with baseline systolic pressure of 141 to 179 mm Hg, those with systolic pressure < or = 140 mm Hg had a significantly higher risk of dementia (relative risk (RR) = 1.9, 95% confidence interval (CI), 1.2-3.2) and Alzheimer's disease (RR = 2.2, 95% CI, 1.2-3.8). However, the RR in relation to systolic pressure < or = 140 mm Hg was 1.3 (0.8-2.2) for all dementia and 1.5 (0.8-2.6) for Alzheimer's disease, when the baseline Mini-Mental State Examination (MMSE) score was included in the model as a dichotomous variable (< 24 vs > or = 24). Baseline MMSE < 24 significantly predicted the occurrence of dementia (RR = 6.9; 95% CI, 4.3-11.1). Systolic pressure < or = 140 mm Hg was significantly related to MMSE score < 24 at baseline. CONCLUSIONS: These data suggest that low blood pressure may be an early correlate of a dementing process although a causative effect cannot be definitely ruled out.

Aged↗

PubMed1999

Volatile organic compound emissions from latex paint--Part 1. Chamber experiments and source model development.

Latex paints are widely used in residential and commercial indoor environments. The surface areas covered by the paints in these environments are relatively large. Thus, latex paints have the potential for having a major impact on indoor air quality (IAQ). A study was undertaken to develop methods for evaluating the impact of latex paint emission on IAQ. Small chamber experiments using stainless steel and painted and unpainted gypsum board substrates were conducted to determine the emission characteristics of latex paint. The emissions from the stainless steel were relatively short lived (3 to 4 days), whereas the emissions from gypsum board lasted for over 200 days. Because gypsum board is a common substrate for latex paint, all emission models were developed for the gypsum board substrates. The data from the small chamber tests led to the development of two empirical and two mass-transfer-based source emission models. Approximately 100 to 200 days of data were required to estimate the parameters required for the empirical models. Only 8 days of data were required to estimate the parameters for the mass-transfer-based models. The final models use paint formulation and mass transfer correlations to predict the emissions of the major individual volatile organic compounds emitted by latex paint.

Air Pollution, Indoor↗

PubMed1999

Volatile organic compound emissions from latex paint--Part 2. Test house studies and indoor air quality (IAQ) modeling.

Emission models developed using small chamber data were combined with an Indoor Air Quality (IAQ) model to analyze the impact of volatile organic compound (VOC) emissions from latex paint on indoor environments. Test house experiments were conducted to verify the IAQ model's predictions. The agreement between model predictions and experimental measurements met the American Society for Testing and Materials criteria for model verification in the room with the source and met most of the requirements in other rooms. The major cause of disagreement between the model predictions and the experimental data in the test house appears to be an inadequate sink model.

Air Pollution, Indoor↗

PubMed1999

Effects of glycyrrhizin on production of vascular aldosterone and corticosterone.

This study is to confirm the role of glycyrrhizin on blood pressure and to test the effects of glycyrrhizin on production of vascular aldosterone and corticosterone in rats. Male Wistar rats received glycyrrhizin (Sigma) 200 mg/kg/day p.o. for 5 weeks, and blood pressure was monitored by a pressure transducer. Systolic blood pressure significantly increased in Wistar rats treated with glycyrrhizin compared to that without glycyrrhizin. Mesenteric artery perfusion ex vivo and pressor responses to norepinephrine were performed. The pressor responses to norepinephrine in mesenteric arteries treated with glycyrrhizin were significantly increased. The perfusate from the mesenteric arteries was collected and applied to a Sep-Pak C 18 cartridge column, used for reverse-phase high-performance liquid chromatography, and measured for both aldosterone and corticosterone by radioimmunoassay. Levels of aldosterone were decreased but those of corticosterone increased in perfusate from arteries treated with glycyrrhizin. RT-PCR showed that glycyrrhizin inhibited the expression of 11beta- HSD2 and CYP11B2 mRNA in mesenteric arteries. These results confirm that glycyrrhizin is able to induce hypertension, and provide evidence that it inhibits the transcriptions of both 11beta-HSD2 and CYP11B2 in the vasculature, leading to lower aldosterone and higher corticosterone production in vessels, and increased vasoconstrictor responses to norepinephrine.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1999

Regional postprandial fatty acid metabolism in different obesity phenotypes.

To examine if postprandial splanchnic/hepatic free fatty acid (FFA) delivery is increased in upper-body (UB) obesity, and to determine the adipose tissue depots responsible for the greater postprandial FFA availability, we measured systemic and regional uptake and release of FFAs ([1-(14)C]palmitate) before and during a 5-h frequent-feeding mixed meal in eight UB and eight lower-body (LB) obese women. Postabsorptive FFA flux and splanchnic FFA delivery were not different in UB and LB obese women; however, postprandial FFA concentrations (257 +/- 45 vs. 81 +/- 12 micromol/l, P < 0.0001), FFA flux (8.5 +/- 1.2 vs. 3.9 +/- 0.8 micromol x kg(-1) fat-free mass x min(-1), P < 0.0001), splanchnic FFA delivery (275 +/- 45 vs. 88 +/- 24 micromol/min, respectively, P < 0.005), and estimated hepatic FFA delivery were greater in UB than LB obese women. Nonsplanchnic UB adipose tissue FFA release was greater in UB than in LB obese women (276 +/- 71 vs. 97 +/- 37 micromol/min, respectively, P < 0.05) and accounted for the greater postprandial FFA availability in UB obesity. Postprandial leg glucose uptake was less in UB than in LB obese women (8.4 +/- 5.1 vs. 22.9 +/- 2.6 micromol x kg(-1) leg fat-free mass x min(-1), P < 0.05). We conclude that the elevated postprandial FFA release observed in UB obese women originates from the nonsplanchnic UB fat, not visceral fat. These results suggest that visceral fat may be a marker for, but not the source of, excess postprandial FFAs in obesity.

Adult↗

PubMed1999

Structural studies of initial lymphatics adjacent to gastric and colonic malignant neoplasms.

Invasion and metastases are the main causes of death from cancer, and prognosis is best correlated with invasion of malignant cells into initial lymphatics and dissemination to regional lymph nodes. Using both light and transmission electron microscopy, we examined human gastric and colonic cancers and their relation to initial lymphatics. Invasion of malignant tumor cells into the initial lymphatics was characterized by interdigitating and overlapping endothelium giving way to open junctions as lymphatic endothelial cells were apparently dissolved and destroyed. Cytoplasmic vesicles, mitochondria, and rough endoplasmic reticulum were qualitatively increased as demonstrated by image analysis.

Colonic Neoplasms↗

PubMed1999

[The genotype-based haplotype relative risk and transmission disequilibrium test analyses of familial febrile convulsions].

OBJECTIVE: To confirm the linkage of familial febrile convulsions to the short arm of chromosome 6(6p) or the long arm of chromosome 8(8q). METHODS: The authors finished genotyping of Pst I locus on the coding region of heat shock protein (HSP) 70, 5'untranslated region of HSP70-1, 3' untranslated region of HSP70-2, D8S84 and D8S85. The data were processed by the genotype-based haplotype relative risk(GHRR) and transmission disequilibrium test(TDT) methods in PPAP. RESULTS: Some signs of association and disequilibrium between D8S85 and FC were shown by GHRR and TDT. CONCLUSION: A suspect linkage of familial febrile convulsions to the long arm of chromosome 8 has been proposed.

Chromosomes, Human, Pair 6↗

PubMed1999

Effect of tumor necrosis factor-alpha and interleukin-2 on spleen lymphocyte migration in mouse skin.

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) are reported to enhance lymphocyte binding to endothelial cells in vitro. We examined these two agents on lymphocyte migration in vivo. Spleen lymphocytes were radiolabeled with tritiated uridine (3H-UR) and then injected i.v. into mice. Each cytokine (TNF-alpha or IL-2) or both cytokines were then injected intradermally on the back of mice. The results demonstrated that TNF-alpha stimulates lymphocyte migration in vivo in dose-dependent fashion. Kinetic analysis demonstrated that migration with TNF-alpha started at 3 h, peaked at 6 h, followed by a gradual decline back to baseline at 24 h. IL-2, on the other hand, was nearly inactive, and did not augment lymphocyte migration over and above that induced by TNF-alpha when both cytokines were injected together.

Animals↗