Biomedical subjects

R Zhou

Publications and source records attributed to R Zhou.

At least 19 recordsLinked to original sources

PubMed2006

Non-lethal freezing effects on seed degreening in Brassica napus.

The effects of a non-lethal freezing stress on chlorophyll content, moisture level and distribution, and abscisic acid (ABA) levels were examined in siliques and seeds of Brassica napus (canola). A non-lethal freezing stress resulted in the retention of chlorophyll in seed at harvest that was most pronounced for seeds 28, 32 and 36 days after flowering (DAF). This increase was primarily due to an increased retention of chlorophyll a relative to chlorophyll b. Chlorophyll retention in seeds exposed to a non-lethal freezing stress correlated with an increased ABA catabolism, as measured 1, 3 or 7 days after the stress treatment. Although the non-lethal freezing stress had no significant effect on moisture content in seeds of siliques stressed at 28-44 DAF, moisture distribution, as viewed by magnetic resonance imaging, showed an uneven drying of 32 and 40 DAF siliques after exposure to the non-lethal freezing stress. Moisture was initially lost more rapidly from the silique wall between seeds, than in control non-stressed siliques. Increased moisture loss was not due to structural changes in the vasculature of the silique/seed of stressed tissues. These results are consistent with the hypothesis that a non-lethal freezing stress-induced decrease in ABA level, during seed maturation, effects an inhibition of normal chlorophyll a catabolism resulting in mature but green B. napus seed.

Abscisic Acid↗

PubMed2006

T1-weighted cine FLASH is superior to IR imaging of post-infarction myocardial viability at 4.7T.

PURPOSE: Data are unavailable for rational selection of pulse sequences to assess postinfarction myocardial viability in rodents at high field strength. We implemented a widely used clinical inversion recovery (IR) sequence at 4.7T and compared the results to a heavily T1-weighted cine FLASH sequence (T1-CF) for assessment of infarction size. MATERIALS AND METHODS: Eleven infarcted rats were examined within 24 h of infarction after injection of Gadophrin-3 contrast agent. Images were acquired using both pulse sequences and a standard cine (SC) sequence. Estimates of infarct size were compared to TTC. Global LV function was compared between the T1-CF and SC sequences. RESULTS: SNR, relative SNR, and CNR for the infarcted and normal myocardium were significantly greater for the IR sequence. Infarction size was overestimated by both sequences, but correlated highly and showed very close agreement with TTC. Global function revealed no significant differences between T1-CF and SC. CONCLUSION: Both IR and T1-CF produced reliable results for assessment of infarction size at 4.7T. While the IR sequence delivers better overall SNR and CNR, the T1-CF allows concomitant assessment of global cardiac function with a much shorter acquisition time.

Animals↗

PubMed2005

Methylmercury alters Eph and ephrin expression during neuronal differentiation of P19 embryonal carcinoma cells.

Developmental exposure to methylmercury (MeHg) induces a spectrum of neurological impairment characterized by cognitive disturbance, sensory/motor deficit, and diffuse structural abnormalities of the brain. These alterations may arise from neural path-finding errors during brain development, resulting from disturbances in the function of morphoregulatory guidance molecules. The Eph family of tyrosine kinase receptors and their ligands, the ephrins, guide neuronal migration and neurite pathfinding mainly via repulsive intercellular interactions. The present study examined the effects of MeHg on mRNA and protein expression profiles of Ephs and ephrins in the P19 embryonal carcinoma (EC) cell line and its neuronal derivatives. Undifferentiated control P19 cells displayed low- to undetectable levels of mRNA for ephrins or Ephs, with the sole exception of EphA2 which was highly expressed. Upon differentiation into neurons, the ephrin expression increased progressively through day 10. Similarly, expression of the Ephs, including EphsA3, -A4, -A8, -B2, -B3, -B4, and -B6, increased significantly. In contrast, EphA2 expression decreased in day 2, 6 and 10 control neurons. Treatment with MeHg did not affect the expression of mRNA for ephrins or Ephs in undifferentiated P19 cells. However, treatment of differentiating neurons with MeHg for 24 h caused consistent increases in ligand mRNA expression, particularly ephrin-A5, -A6, -B1, and -B2. Similarly, MeHg induced variable increases in mRNA expression of receptors EphA2, -A3, -B3, and -B6. A trend toward a concentration-response relationship was observed for the alterations in Eph receptor mRNA expression although increases at the low and mid concentrations did not reach statistical significance. Immunoblots for ligand and receptor proteins mirrored the increases in the mRNA levels at the 0.5 and 1.5 microM MeHg concentrations but showed decreased protein levels compared to controls at the 3.0 microM concentration. Alterations in the Eph/ephrin family of repulsion molecules may represent an important mechanism in developmental MeHg neurotoxicity.

Cell Differentiation↗

PubMed2005

[Comparison of homogenous strain-analysis with wall thickening for the MR tomographic assessment of regional myocardial function].

PURPOSE: To compare strain analysis and wall thickening (WT) analysis in differentiating the infarcted, adjacent, and remote zones in a rat model of myocardial infarction (MI). MATERIAL AND METHODS: Three normal (NL) and ten rats subjected to myocardial infarction were imaged on a 4.7T scanner. Gradient-echo and SPAMM-tagged cine images were acquired at three short axis levels of the left ventricle (LV). A homogenous strain analysis (principal strains lambda1 and lambda2, displacement D, angle beta) and a WT-analysis (mm- and %-thickening) were performed in all slices demonstrating MI. Regional function was compared between infarcted rats (infarcted, adjacent and remote zone) and corresponding regions in the NL rats. Additional segmental analysis was performed in the NL rats for the anterior, lateral, inferior and septal wall. RESULTS: In the NL rats, lambda (1) (greatest radial thickening) was greatest in the lateral and anterior wall. WT-analysis showed a pattern of function similar to lambda1, however, regional differences using WT-analysis were not significant. lambda (2) (greatest circumferential shortening) was most negative in the anterior wall. D was greatest in the lateral and inferior wall. The angle beta was radially directed in all segments. In the infarcted rats, both strain and WT-analyses revealed significant impairment in function in the infarcted and adjacent zones as compared to NL (p < 0.001). However, only the strain analysis (lambda1, lambda2, p < 0.001) detected significant remote myocardial dysfunction. Myocardial function differed significantly between the infarcted and adjacent and between the infarcted and remote regions. Strain analysis (lambda2, D, beta, p < 0.001) also identified significant functional differences between the adjacent and remote zones, however, no statistically significant differences were found using WT-analysis. CONCLUSION: Strain analysis is superior to WT-analysis in detecting regional functional variations in NL rats and in discriminating function in the infarcted, adjacent and remote zones post MI.

Algorithms↗

PubMed2005

Imaging reporter genes for cell tracking with PET and SPECT.

Transplantation of cells into damaged tissue has tremendous therapeutic potential in a number of disorders, such as Parkinson's disease and myocardial infarction. Positron emission tomography (PET) and single photon emission tomography (SPECT) are highly sensitive imaging modalities, which can detect and track these cellular implants through a number of mechanisms. The stable transfection of cells with a reporter gene, which can be visualized using a radioactive PET or SPECT reporter probe, allows the repeated visualization of the migration and function of cells. These imaging techniques can be used to assess cell trafficking with methods that are easily translatable to humans. This review describes several reporter genes for PET and SPECT, and compares them against other techniques and imaging modalities.

Animals↗

PubMed2004

Quantitative assessment of regional myocardial function in a rat model of myocardial infarction using tagged MRI.

We characterized global and regional left ventricular (LV) function during post myocardium infarction (MI) remodeling in rats, which has been incompletely described by previous MRI studies. To assess regional wall motion, four groups of infarcted animals corresponding to 1-2, 3-4, 6-8 and 9-12 weeks post-MI respectively were imaged using a fast gradient echo sequence with a 2D spatial modulation of magnetization (SPAMM) tagging preparation. An additional group was serially imaged (1-2 and 6-7 weeks post-MI) to assess the global function. Regional and global functional parameters of infarcted rats were compared to non-infarcted normal rats. Compared to normal rats, a decrease in ejection fraction (70 +/-7 vs. 40 +/- 8%, p<0.05) was observed in rats with MI. Maximal and minimal principal stretches (lambda1, lambda2) and strains (E1, E2), principal angle (beta) and displacement varied regionally in normal rats but deviated significantly from the normal values in rats with MI particularly in the infarcted and adjacent zones. Not only was strain magnitude reduced segmentally post-MI, but strain direction became more circumferentially oriented, particularly in rats with larger infarctions. We report the first regional myocardial strain values in normal and infarcted rats. These results parallel findings in humans, and provide a unique tool to examine regional mechanical influences on the remodeling process.

Algorithms↗

PubMed2004

Neurochemical and behavioral deficits consequent to expression of a dominant negative EphA5 receptor.

The Eph family tyrosine kinase receptors and their ligands have been linked to axon guidance and topographic mapping of the developing central nervous system. More specifically, the EphA5 receptor has been shown to play a role in development of hippocamposeptal, retinotectal and thalamocortical projections. Recently, a line of transgenic mice was developed which expresses a truncated EphA5 receptor lacking a functional tyrosine kinase domain. In a previous study, axonal tracing revealed that medial hippocampal axons in this strain projected laterally and ventrally away from their normal target area. In the current study, both transgenic and wild-type controls were evaluated in unconditioned (rotorod and locomotor activity) and conditioned (water maze and active avoidance) behavior tasks which tested hippocampal and striatal functioning. Compared to controls, the transgenic strain did not show differences in rotorod motor activity but did show a transient deficit in spatial navigation ability and a consistent impairment in active avoidance. The dominant-negative mutant receptor also resulted in a decrease in striatal dopamine and serotonin concentrations with no change in hippocampal monoamines. Collectively, these data suggest that animals expressing a truncated EphA5 receptor show deficits related to striatal functioning.

Animals↗

PubMed2004

Prothrombin Shanghai: hypoprothrombinaemia caused by substitution of Gla29 by Gly.

Prothrombin deficiency is a rare bleeding disorder inherited as an autosomal recessive trait. In this study, we reported a Chinese family with hereditary prothrombin deficiency. The proposita had a prolonged activated partial thromboplastin time (APTT, 71.6 s) and prothrombin time (PT, 28.0 s). The coagulation factors activities were normal except that prothrombin coagulation activity was markedly reduced, and the prothrombin antigen level was moderately decreased. Nucleotide sequencing of amplified DNA revealed a novel mutation, Glu (GAG) to Gly (GGG) at residue 29, which normally undergoes gamma-carboxylation within the Gla domain of prothrombin. The proposita was identified as homozygous, while her father, mother and maternal grandmother were heterozygous for the mutation. Gla29 has been demonstrated as one of the key residue for Ca2+-binding, membrane interaction and biological activity of prothrombin.

Amino Acid Substitution↗

PubMed2004

Insulin-like growth factor-binding protein-4 inhibits growth of the thymus in transgenic mice.

Numerous in vitro studies have demonstrated that IGF-binding protein (IGFBP)-4 is a consistent inhibitor of IGF actions. In order to investigate the functions of IGFBP-4 in vivo, transgenic mice were generated by microinjection of a transgene, in which the murine Igfbp4 cDNA is driven by the H-2K(b) promoter, and followed by a splicing cassette and polyadenylation signal of the human beta-globin gene. Transgene mRNA was expressed ubiquitously, and elevated IGFBP-4 protein was detected in the spleen, thymus, kidney and lung of transgenic mice. The activities of serum IGFBPs were not changed in transgenic mice. Immunohistochemical studies revealed transgene expression predominantly in the thymic medulla and red pulp of the spleen. Body weight and the weights of the spleen, kidney and lung of transgenic mice were not different from controls. In contrast, the thymus of transgenic mice showed a significantly reduced weight and cortex volume. In transgenic thymus and spleen, cell proliferation was inhibited and apoptosis was stimulated. Transgenic mice showed normal T- and B-cell development and normal basal plasma immunoglobulin levels. In conclusion, overexpression of IGFBP-4 inhibits growth of the thymus. IGFBP-4 excess inhibits cell proliferation and stimulates apoptosis in lymphoid tissues, but does not affect lymphocyte development. These findings suggest that IGFBP-4 is a potential growth inhibitor of lymphoid tissues.

Animals↗

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

The rice field eel as a model system for vertebrate sexual development.

Complex developmental mechanisms of vertebrates are unraveled using comparative genomic approaches. Several teleosts, such as zebrafish, medaka and pufferfish, are used as genetic model systems because they are amenable to studies of gene function. The rice field eel, a freshwater fish, is emerging as a specific model system for studies of vertebrate sexual development because of its small genome size and naturally occurring sex reversal. Data presented here support the use of the rice field eel as another important fish model for comparative genome studies, especially in vertebrate sexual development. This model system is complementary rather than redundant.

Animals↗

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↗