Biomedical subjects

R Zhou

Publications and source records attributed to R Zhou.

At least 19 recordsLinked to original sources

PubMed2003

A novel assay for discovery and characterization of pro-apoptotic drugs and for monitoring apoptosis in patient sera.

We have developed an apoptosis assay based on measurement of a neoepitope of cytokeratin-18 (CK18-Asp396) exposed after caspase-cleavage and detected by the monoclonal antibody M30. The total amount of caspase-cleaved CK18 which has accumulated in cells and tissue culture media during apoptosis is measured by ELISA. The sensitivity is sufficient for use in the 96-well format to allow high-through-put screening of drug libraries. We here describe strategies allowing classification of pro-apoptotic compounds according to their profiles of induction of apoptosis in the presence of pharmacological inhibitors. The time course of induction of CK18 cleavage can furthermore be used to distinguish structurally similar compounds. We propose that compounds that induce rapid CK18 cleavage have mechanisms of actions distinct from conventional genotoxic and microtubuli-targeting agents, and we present one example of an agent that induces almost immediate mitochondrial depolarization and cytochrome c release. Finally, CK18-Asp396 cleavage products are released from cells in tissue culture, and presumably from tumor cells in vivo. These products can be measured in sera from cancer patients. We present evidence suggesting that it will be possible to use the M30-ELISA assay for measuring chemotherapy-induced apoptosis in patient sera, opening possibilities for monitoring therapy.

Antibodies, Monoclonal↗

PubMed2003

Correlation between periodontal status and biting ability in Chinese adult population.

This study investigated the relation between periodontal condition and biting ability in a Chinese population using the pressure-detecting sheet. A total of 142 subjects residing in Nanchang, Jiangxi province, China, participated in the study. The examination included probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing and coronal caries teeth. Biting abilities per person, biting force, biting pressure and occlusal contact area were measured using the sheet. Number of teeth present showed positive correlation with biting force and occlusal contact area, but were negatively correlated with biting pressure. No significant correlation was observed between the mean PD, percentage of pocket > or = 4 mm, bleeding index and any of biting abilities. The mean CAL showed a significantly negative correlation with biting force and occlusal contact area. Multiple stepwise regression analysis selected the number of teeth present, sex and age as the significant factors affecting the biting ability. However, no periodontal indices were picked up as the significantly contributing factor. There appears to be little effect of periodontal condition on biting ability. Ageing was selected as a contributing factor to reduction in the Chinese adults, but not in the Japanese population.

Adult↗

PubMed2003

IGF-binding protein-4: biochemical characteristics and functional consequences.

IGFs have multiple functions regarding cellular growth, survival and differentiation under different physiological and pathological conditions. IGF effects are modulated systemically and locally by six high-affinity IGF-binding proteins (IGFBP-1 to -6). Despite their structural similarity, each IGFBP has unique properties and exhibits specific functions. IGFBP-4, the smallest IGFBP, exists in both non-glycosylated and N-glycosylated forms in all biological fluids. It is expressed by a wide range of cell types and tIssues, and its expression is regulated by different mechanisms in a cell type-specific manner. IGFBP-4 binds IGF-I and IGF-II with similar affinities and inhibits their actions under almost all in vitro and in vivo conditions. In this review, we summarize the available data regarding the following aspects of IGFBP-4: genomic organization, protein structure-function relationship, expression and its regulation, as well as IGF-dependent and -independent actions. The biological significance of IGFBP-4 for reproductive physiology, bone formation, renal pathophysiology and cancer is discussed.

Animals↗

PubMed2001

[Sequential BiPAP following invasive mechanical ventilation in COPD patients with hypercapnic respiratory failure].

OBJECTIVE: To estimate the feasibility and the efficacy of extubation and sequential bilevel positive airway pressure (BiPAP) in chronic obstructive pulmonary disease (COPD) patients with exacerbated hypercapnic respiratory failure. METHODS: All patients were randomly divided into a control group and an experimental group. In addition to conventional therapy, the experimental group was treated with bilevel positive airway pressure via facial mask immediately, the control group was treated with conventional therapy alone. RESULTS: There were no difference in clinical characteristics and gas exchange at entry. pH value, PaCO2 and PaCO2 were significantly improved in experimental group following the first 45 minutes ventilation (P < 0.05), but no additional improvement was observed when ventilation was extended to 12 hours (P > 0.05). Reintubation rate was higher in the control group compared with the experimental group (P < 0.05). CONCLUSION: BiPAP can be well tolerated, and can improve ventilation function markedly. It can also facifiated the extubation, and reduced the reintubation rate in regular mechanical ventilation.

Aged↗

PubMed2001

The free energy landscape for beta hairpin folding in explicit water.

The folding free energy landscape of the C-terminal beta hairpin of protein G has been explored in this study with explicit solvent under periodic boundary condition and OPLSAA force field. A highly parallel replica exchange method that combines molecular dynamics trajectories with a temperature exchange Monte Carlo process is used for sampling with the help of a new efficient algorithm P3ME/RESPA. The simulation results show that the hydrophobic core and the beta strand hydrogen bond form at roughly the same time. The free energy landscape with respect to various reaction coordinates is found to be rugged at low temperatures and becomes a smooth funnel-like landscape at about 360 K. In contrast to some very recent studies, no significant helical content has been found in our simulation at all temperatures studied. The beta hairpin population and hydrogen-bond probability are in reasonable agreement with the experiment at biological temperature, but both decay more slowly than the experiment with temperature.

Amino Acid Sequence↗

PubMed2001

Ephrins stimulate neurite outgrowth during early cortical neurogenesis.

The Eph receptor ligands, the ephrins, are membrane-bound molecules that play important roles in establishing intercellular communication after neurogenesis by regulating cell migration, axon pathfinding, and topographic mapping. In diverse systems, such as embryonic day 17.5 (E17.5) hippocampal and cortical neurons, repulsive/inhibitory mechanisms underlie these cellular effects. However, although ligand/receptor expression occurs far earlier, during brain neurogenesis, little is known about potential ephrin functions in initial process outgrowth. We have examined ligand/receptor expression in E13.5 cortex in vivo and in culture, using alkaline phosphatase (AP)-conjugated reagents and RNase protection assay. B ephrins are highly expressed, including B1, B2, and B3, whereas A ephrins exhibit low expression levels. In contrast, the Eph receptors demonstrate an opposite pattern, exhibiting high levels of Eph A3, A4, and A5 mRNA transcripts and low levels of the B-class receptors. To examine effects on neurite outgrowth, soluble ephrins were incubated with antihuman IgG antibody, producing oligomeric agonist complexes, and dried onto culture dishes. Unexpectedly, both ephrin A and B complexes increased process outgrowth: Seventy to eighty percent of neuronal precursors exhibited long neurites on ephrins, whereas only 5-10% of cells had neurites on IgG control substrates, indicating that ephrins stimulated neuritogenesis by early cortical neurons. These observations suggest that ephrin ligand/receptor systems play ontogenetic roles not previously considered, activating mechanisms other than cellular repulsion. Ephrin systems may induce initial process elaboration by early cortical neurons that is restricted at later stages by well-characterized repulsive signaling mechanisms.

Animals↗

PubMed2001

Insulin-like growth factor-binding protein-5 inhibits growth and induces differentiation of mouse osteosarcoma cells.

The precise role of insulin-like growth factor-binding protein-5 (IGFBP-5) in regulating the growth of tumor cells, especially of bone-derived malignant cells, is not well understood. We have investigated the biological activity of IGFBP-5 by transfecting OS/50-K8 mouse osteosarcoma cells with an expression vector containing the osteocalcin promoter and the complete mouse IGFBP-5 cDNA (OC-IGFBP-5). Overexpression of IGFBP-5 mRNA and secretion of increased amounts of bioactive protein in conditioned media were demonstrated in different clones. For the analysis of cell proliferation, three clones exhibiting high levels of IGFBP-5 expression were selected and compared to a mock clone and to nontransfected parental cells. IGFBP-5-secreting clones displayed reduced proliferation under both anchorage-dependent and -independent conditions (P < 0.05). The increase in proliferation observed in IGFBP-5-secreting clones after addition of exogenous IGF was significantly lower than that observed in mock-transfected or parental cells. A similar result was obtained with long[R3]IGF-I which has a low affinity for all IGFBPs, suggesting that the inhibitory effect of IGFBP-5 is only partially IGF-dependent. OC-IGFBP-5-transfected clones expressed significantly higher amounts of osteocalcin mRNA (P < 0.05) and secreted more osteocalcin protein than a mock clone or parental OS-50/K8 cells. Thus, part of the growth-inhibiting effect of IGFBP-5 may be due to an induction of differentiation in these cells.

Animals↗

PubMed2001

Design and synthesis of irreversible depsipeptidyl human rhinovirus 3C protease inhibitors.

Novel tripeptidyl C-terminal Michael acceptors with an ester replacement of the P(2)-P(3) amide bond were investigated as irreversible inhibitors of the human rhinovirus (HRV) 3C protease (3CP). When screened against HRV serotype-14 the best compound was shown to have very good 3CP inhibition (k(obs)/[I]=270,000M(-1)s(-1)) and potent in vitro antiviral activity (EC(50)=7.0nM).

3C Viral Proteases↗

PubMed2001

TGF-alpha induces a stationary, radial-glia like phenotype in cultured astrocytes.

Transgenic mice studies have suggested that transforming growth factor-alpha (TGF-alpha) influences the postnatal differentiation of astrocytes. To understand the role of TGF-alpha during astrocytic differentiation, it is important to determine how this factor affects astrocytes in the absence of other influences. We have thus examined in vitro under serum-free medium conditions the effect of TGF-alpha on the properties of astrocytes derived from the cerebral cortex of newborn rats. When TGF-alpha is added to serum-free medium, most astrocytes lose their polygonal shape and extend two long processes running in opposite directions. This bipolar morphology strikingly resembles that of radial glial cells. Intriguingly, serum inhibits this morphological transformation. TGF-alpha also triggers an increase in glial fibrillary acidic protein (GFAP) expression and a decrease in nestin expression. Another major effect of TGF-alpha is to practically abolish the motility of astrocytes. TGF-alpha, however, does not appear to influence the proliferation and apoptosis of astrocytes. These results suggest that polygonal astrocytes are derived primarily from radial glial cells, and that in vivo TGF-alpha may be instrumental in determining the shape and migratory potential of radial glial cells.

Aging↗

PubMed2001

[Influence of zafirlukast on pulmonary functions and quality of life in patients with asthma].

OBJECTIVES: To explore the influence of zafirlukast on pulmonary functions and quality of life (QOL) in patients with mild-to-moderate asthma at the stage of attack and at the stable stage. METHODS: Patients at the stage of attack were randomly divided into two groups: Group one is zafirlukast 20 mg twice daily plus inhaled the half quantity of glucocorticoid(budelade) of the Global Initiative for Asthma (GINA) standard quantity, long-effection aminophyllin 0.2 g twice daily and inhaled salbutamol when necessary; Group two: inhaled budelade of GINA standard quantity, long-effection aminophyllin 0.2 g twice daily and inhaled salbutamol when necessary). Patients' peak expiratory flow (PEF)/PEF predicted value % and delta PEFR% were determined at the second week and the forth week before and after the treatment. On the standard treatment, patients with the stable stage were added zafirlukast 20 mg twice a day. PEF values in the morning and evening and QOL were evaluated. RESULTS: After treating with zafirlukast, the PEF/PEF predicted value % and delta PEFR% in Group one were higher and lower than those of Group two respevtively. These changes were appeared in two days and were peaked in two weeks and the peak had been gone on for more than 4 weeks, but these were no significant difference between the Groups (P > 0.05); PEF values in the morning and evening in patients with the stable asthma increased 5.9% and 4.6% respectively and their QOL were improved in asthma symptoms, limitative activities, avoiding stimuli, and reacting on stimuli. CONCLUSION: Zafirlukast can improve pulmonary function, reduce the inhalation quantity of steroid in patients with mild-to-moderate asthma, and play an important role in treating and improving QOL in patients with the stable asthma.

Adolescent↗

PubMed2001

[Effects of noninvasive positive pressure ventilation on gas exchange and patients' transformation in chronic obstructive pulmonary disease and respiratory failure].

OBJECTIVE: This paper was to observe the effects of noninvasive positive pressure ventilation (NPPV) on gas exchange and patients' transformation and to evaluate their clinical value. METHODS: Patients were randomly treated by either NPPV, or conventional medicine. The arterial blood gas readings, heart rates (HR), and respiratory rates (HR) were obtained at admission after the treatment. It was necessary to intubate when the clinical deterioation was marked by PaCO2 > 70 mmHg, PaCO2 gradually increasing 5-10 mmHg, pH decreasing 0.05-0.1 or mental obstacle, or PaO2 < 45 mmHg. RESULTS: NPPV significantly decreased the PaCO2 level, HR, and RR, significantly increased the PaO2 level, and also decreased the opportunity of intubation. CONCLUSION: The results suggest that NPPV can improve the gas exchange and reduce the need of intubation in COPD patients with acute respiratory failure.

Aged↗

PubMed2001

Determination of etoposide in human plasma and leukemic cells by high-performance liquid chromatography with electrochemical detection.

This paper describes a high-performance liquid chromatographic method with electrochemical detection for the determination of etoposide levels in plasma, total and non-protein bound concentration, and in leukemic cells. The precision for between-runs (n=6) was 7.0, 4.9, and 9.5%, the accuracy was 3.7, 7.1 and 6.3%, and within-runs precision (n=6) was 3.9, 2.9 and 5.1% for total plasma, non-protein bound plasma fraction and leukemic cells, respectively. The correlation coefficients (R2) were 1.00 for all calibration curves. These assays have been applied to analyze samples from one patient with acute myelogenous leukemia during 24 h after i.v. infusion of etoposide (100 mg/m2).

Antineoplastic Agents, Phytogenic↗

PubMed2001

Synthesis and characterization of oxidized W(6)S(8)L(6) clusters.

Cationic [W(6)S(8)L(6)]PF(6) (L = PEt(3) (3), 4-tert-butylpyridine (4)) clusters were successfully synthesized and isolated for the first time by reacting the corresponding neutral W(6)S(8)L(6) (L = PEt(3) (1), 4-tert-butylpyridine (2)) clusters with [Cp(2)Fe]PF(6) as the oxidant. The products 3 and 4 were characterized by NMR spectroscopy, mass spectroscopy, and X-ray crystallography (only for 3) and shown to be the desired oxidized W(6)S(8) clusters with a metal electron count of 19. Magnetic property studies showed that they are paramagnetic compounds with S = (1)/(2). Their chemical properties and stability are also reported. Crystal data for 3.2 THF: space group, R3 (No. 148); a = 13.91170(10) A; c = 32.4106(2) A; Z = 3.

Journal Article↗

PubMed2001

Synthesis, characterization, and ligand exchange studies of W(6)S(8)L(6) cluster compounds.

Eleven organic Lewis bases were investigated as potential ligands (L) on W(6)S(8)L'(6) clusters by exploring ligand exchange reactions to form W(6)S(8)L(6) clusters. Six new homoleptic W(6)S(8)L(6) cluster complexes were prepared and characterized with L = tri-n-butylphosphine (P(n)Bu(3)), triphenylphosphine (PPh(3)), tert-butylisocyanide ((t)BuNC), morpholine, methylamine (MeNH(2)), and tert-butylamine ((t)BuNH(2)). While partial replacement of ligands occurred with diethylamine (Et(2)NH) and dibutylamine (Bu(2)NH), homoleptic clusters could not be prepared by these exchange reactions. When aniline, tribenzylamine, and tri-tert-butylphosphine were the potential ligands, no exchange was observed. From ligand exchange studies of these ligands and others previously studied, a thermodynamic series of binding free energies for ligands on W(6)S(8)L(6) clusters was established as the following: non-Lewis base solvents, aniline, P(t)()Bu(3), etc. << Et(2)NH, Bu(2)NH < (t)BuNH(2) < morpholine, piperidine < or = (n)BuNH(2), MeNH(2) < or = 4-tert-butylpyridine, pyridine < (t)BuNC < tricyclohexylphosphine (PCy(3)) < PPh(3), P(n)Bu(3) < or = triethylphosphine (PEt(3)). Structures of the new cluster complexes were determined by X-ray crystallography. The new compounds were also characterized by NMR spectroscopy and thermogravimetric analyses (TGA). The W-L bond orders and TGA data qualitatively agree with the thermodynamic series above.

Journal Article↗

PubMed2001

Mass transport characteristics and chromatographic behavior of preparative electrochromatography on hydroxyapatite.

Introducing an electric field into chromatography on hydroxyapatite (HAP) was attempted in order to enhance mass transfer and separation performance. A membrane spaced multicompartment electrolyzer was developed for electrochromatography on HAP. The high performance of liquid transport by electroosmotic flux was identified and described in terms of dynamic electroosmotic pressure. The application of the electric field resulted in an improved adsorption of bovine serum albumin as shown by the breakthrough curve as function of the electric field. An improved elution was also obtained in the presence of the electric field. The results show that electroosmosis is a powerful tool of liquid transport and dispersion in a packed bed of fine particles and has potential in the large-scale chromatography of biological molecules.

Adsorption↗

PubMed2001

Altered sensitivity of CD81-deficient mice to neurobehavioral effects of cocaine.

CD81, also known as target of the antiproliferative antibody, is known to be expressed in astrocytes and involved in cell adhesion and, recently, we demonstrated its induction exclusively in the accumbens following cocaine. In the present study, the sensitivity of CD81-deficient mice to behavioral effects of cocaine was evaluated. It was found that CD81-deficient mice exhibited altered sensitivity to cocaine as assessed in the place preference conditioning paradigm and locomotor activity. This deficit in place preference conditioning was not accompanied by a deficit in acquisition or retention of water maze behavior. In addition, CD81 knockout mice exhibited higher levels of nucleus accumbens dopamine as compared to their controls. These observations are discussed in the context of the role of CD81 in cocaine-mediated behaviors.

Animals↗

PubMed2001

In vivo detection of gene expression in liver by 31P nuclear magnetic resonance spectroscopy employing creatine kinase as a marker gene.

In vivo assessment of gene expression is desirable to obtain information on the extent and duration of transduction of tissue after gene delivery. We have developed an in vivo, potentially noninvasive, method for detecting virally mediated gene transfer to the liver. The method employs an adenoviral vector carrying the gene for the brain isozyme of murine creatine kinase (CK-B), an ATP-buffering enzyme expressed mainly in muscle and brain but absent from liver, kidney, and pancreas. Gene expression was monitored by (31)P magnetic resonance spectroscopy (MRS) using the product of the CK enzymatic reaction, phosphocreatine, as an indicator of transfection. The vector was administered into nude mice by tail vein injection, and exogenous creatine was administered in the drinking water and by i.p. injection of 2% creatine solution before (31)P MRS examination, which was performed on surgically exposed livers. A phosphocreatine resonance was detected in livers of mice injected with the vector and was absent from livers of control animals. CK expression was confirmed in the injected animals by Western blot analysis, enzymatic assays, and immunofluorescence measurements. We conclude that the syngeneic enzyme CK can be used as a marker gene for in vivo monitoring of gene expression after virally mediated gene transfer to the liver.

Adenoviridae↗

PubMed2001

Comparison of arrhythmias among different left ventricular geometric patterns in essential hypertension.

The differences of arrhythmias among distinct left ventricular geometric patterns in the patients with essential hypertension were studied. 179 patients with essential hypertension received 24 h dynamic ECG recording, ambulatory blood pressure monitoring, echocardiography examination, etc. According to the examinations, left ventricular geometric patterns and arrhythmias were identified. The comparison of morbidity of arrhythmias between the left ventricular remodeling group and the normal geometric pattern group was performed. The multiple stepwise regression analysis was carried out to identify the independent determinants of arrhythmias. After these predictors were controlled or adjusted, the severity of arrhythmias among different left ventricular geometric patterns was compared. It was found that the morbidity of atrial arrhythmia, ventricular arrhythmia and complex ventricular arrhythmias in the left ventricular remodeling group was significantly higher than in the normal geometric pattern group respectively. There were many independent factors influencing on arrhythmias in essential hypertension. Of all these factors, some indices of left ventricular anatomic structure, grade of hypertension, left atrial inner dimension, E/A, diastolic blood pressure load value at night and day average heart rate and so on were very important. After the above-mentioned factors were adjusted, the differences of the orders of arrhythmias between partial geometric patterns were reserved, which resulted from the differences of the geometric patterns. Many factors contributed to arrhythmias of essential hypertension, such as grade of hypertension, LVMI, LA, PWT and so on. The severity of arrhythmias was different in different left ventricular geometric patterns.

Aged↗