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Biomedical subjects

W Zhou

Publications and source records attributed to W Zhou.

At least 37 records · Page 2Linked to original sources

Rapid ESI-MS method for examining the thermal decomposition of pharmaceuticals.

A Finnigan MAT TSQ 700 triple quadrupole mass spectrometer equipped with a Harvard 22 syringe pump has been used to investigate the thermal decomposition of three common pharmaceuticals, acetaminophen, indomethacin, and mefenamic acid. In addition, comparative measurements on these same drugs were carried out by HPLC after thermally degrading them at elevated temperatures in order to evaluate the usefulness of the ESI-MS as a rapid means of determining the relative stability and identifying thermal decomposition products. Similar results were obtained between the two techniques (i.e., the relative rates of decomposition were mefenamic acid > indomethacin > acetaminophen), with the advantage that the ESI-MS approach was much quicker to perform.

Differential Thermal Analysis↗

Spatiotemporal analysis of ERP during chinese idiom comprehension.

The objective of the present study was to elucidate the neural underpinning of Chinese idiom comprehension with spatiotemporal patterns of ERP. Thirteen subjects were required to decide whether the last character of each viewed Chinese four-character idiom was correct or not. Fuzzy c-means algorithm based on shape similarity was applied to segmenting spatiotemporal patterns of ERP. Statistical parametric map of t-statistic (SPM(t)) was performed after realignment according to the referential frame provided by fuzzy clustering in order to overcome temporal mismatch. Within 540 ms post-stimulus onset, the spatiotemporal patterns of ERP under both conditions could be segmented into 7 stages optimally and both share the first four microstates with variant membership functions and durations. SPM(t) presented significant differences in multiple regions in 3 stages: (1) during 120-150 ms, the early right hemispheric negativities (ERHN) inboth frontal and temporoparietal areas were likely to reflect both initial syntactic processing and visual word-form mismatch; (2) during 320-380 ms (the N400 stage), negative deflections in left frontal, left anterior temporal, centrofrontal regions might coordinate and integrate both syntactic and semantic analysis in extensive right hemisphere; (3) during 480-540 ms (the P600 stage), positive deflections in left temporoparietal and occipital regions seemed to reflect the reanalysis and the integration of word meanings to obtain the over all meaning of idioms. Our study has implicated the brain mechanism of language comprehension common to alphabetic language as well as that specialized in logographic language.

Adult↗

Effect of hydrostatic pressure gradients and Na2EDTA on permeability of human Schlemm's canal cell monolayers.

PURPOSE: Elevated intraocular pressure in those with glaucoma appears to be a function of increased resistance to movement of aqueous humor through the conventional outflow pathway. The majority of resistance in both normal and glaucomatous eyes is generated in the region between the juxtacanalicular trabecular meshwork and the inner wall of Schlemm's canal. To accommodate transient elevations in pressure, we hypothesize that conventional outflow increases rapidly due to changes in complexity of intercellular junctions between cells of the inner wall of Schlemm's canal. METHODS: To test this hypothesis we examined specifically the effects of hydrostatic pressure gradients and the calcium chelator, Na2EDTA, on permeability of cultured human Schlemm's canal cell monolayers in isolation. Human Schlemm's Canal cells were isolated, cultured and then seeded onto permeable supports and maintained in culture to allow intercellular junctions to mature. With a minimum net transendothelial electrical resistance of 10 Ohm cm2, cells were placed into an Ussing-type chamber and hydraulic conductivity was calculated from pressure and flow measurements that were continuously recorded. Simultaneously, transendothelial electrical resistance was measured manually at fixed intervals. In parallel experiments, cell margins were monitored in real time by videomicroscopy. RESULTS: During the baseline measurement period when cells were exposed to pressure but not Na2EDTA, hydraulic conductivity was constant but transendothelial electrical resistance decreased continuously at rate of 0.24 Ohm cm2/minute. After Na2EDTA treatment, no significant change in transendothelial electrical resistance was measured while, hydraulic conductivity of Schlemm's Canal monolayers increased significantly by 125%; corresponding to noticeable intercellular separations. Restoration of cell-cell contact was observed by videomicroscopy 30 minutes following washout of Na2EDTA and functionally after 2 hours. CONCLUSIONS: Responses of Schlemm's Canal cells to pressure and calcium chelators in vitro are consistent with a role for calcium sensitive junctions in outflow resistance in vivo.

Animals↗

Studies of the thermal degradation of acetaminophen using a conventional HPLC approach and electrospray ionization-mass spectrometry.

The thermal degradation of acetaminophen is studied via conventional accelerated aging studies by initially thermally stressing the compound at temperatures between 160 degrees C and 190 degrees C and measuring the rate of decomposition by reversed-phase high-performance liquid chromatography. Rates of decomposition of the compound in the dry state and the activation energy for the process are determined and compared with previously published kinetic and thermodynamic data for the degradation of acetaminophen in solution. In addition, the thermal fragmentation of acetaminophen under electrospray ionization (ESI) conditions using an interface with a heated capillary inlet is studied and the apparent activation energy for this process also is characterized. A comparison of the data shows that acetaminophen is significantly more stable in the dry state than in solution. However, the gas-phase fragmentation of acetaminophen under ESI conditions occurs more readily than either dry- or solution-state degradation. Although the resulting electrospray fragmentation mimics the breakdown product that is formed when the compound undergoes either acid or base catalyzed hydrolysis in aqueous solutions, the mechanism that produces the fragment ion appears to involve a two-step process. Initially, the parent ion forms of the analyte are produced in the spray region of the interface followed by wall-catalyzed decomposition and re-ionization in the heated inlet capillary of the spectrometer.

Acetaminophen↗

Diversity of vacA and cagA genes of Helicobacter pylori in Japanese children.

BACKGROUND: Helicobacter pylori infection is generally acquired in childhood and persists as an asymptomatic infection for decades in most infected individuals. Only a minority develops a clinical outcome even in childhood, such as peptic ulcer. It has been reported that H. pylori infection with the type I strain, which expresses the VacA and CagA antigen, is associated with peptic ulcer. AIM: We examined the diversity of vacA and cagA genes in isolates obtained from Japanese paediatric patients with peptic ulcer or chronic gastritis to investigate the relationship between genetic diversity and clinical outcome. METHODS: The diversity of vacA and cagA genes was investigated by PCR and sequence analysis in 30 isolates obtained from Japanese paediatric patients with peptic ulcer (eight strains) or chronic gastritis (22 strains). RESULTS: All isolates from Japanese children were cagA-positive strains. Twenty-six strains (86.7%) had East Asian type CagA, and 4 (13.3%) had Western type CagA. The predominant vacA genotype was s1c/m1b (22/30, 73.3%). There was no significant association between the diversity of cagA and vacA genes and clinical outcome. All four children infected with Western CagA strain had a history of overseas travel or residence. CONCLUSION: The predominant genotype of H. pylori in Japanese children is East Asian CagA and vacA s1c/m1b genotype, regardless of clinical outcome. Japanese H. pylori strains are homogeneously of the East Asian type; however, Western strains can be introduced into Japan concomitant with host movement from foreign countries in childhood.

Antigens, Bacterial↗

Regulation of complement C3 and C4 synthesis in human peritoneal mesothelial cells by peritoneal dialysis fluid.

Although complement is activated in the peritoneal cavity during chronic peritoneal dialysis (PD), little is known about its role in peritoneal defence and injury related to long-term PD. We examined the impact of glucose and commercial peritoneal dialysis solutions on complement expression in HPMCs obtained by primary culture from omental tissues of consented patients undergoing elective abdominal surgery. Constitutive expression of C3 and C4 mRNA in HPMCs was up-regulated upon exposure to 75 mm glucose in a time-dependent manner. C3 and C4 protein was secreted in both apical and basolateral directions. Glucose doses beyond 100 mm markedly down-regulated C3 and C4 expression, and stimulated LDH release dose-dependently. Such cytotoxic effects were attenuated using equivalent doses of mannitol instead of glucose. Treatment with conventional lactate-buffered dialysis solution gave rise to down-regulation of C3 and C4 expression, and heightened LDH release in HPMCs. These effects correlated with the glucose strength of the solution, persisted despite replacement with a bicarbonate-buffered solution, aggravated by glycated albumin, and were partially abrogated by supplementation with 10% fetal bovine serum in the culture system. Our findings suggest that the artificial conditions imposed by PD lead to alterations in local complement synthesis that have implications for the role of the peritoneal mesothelium in both inflammation and defence.

Cell Membrane Permeability↗

Seed-to-seed growth of Arabidopsis thaliana on the International Space Station.

The assembly of the International Space Station (ISS) as a permanent experimental outpost has provided the opportunity for quality plant research in space. To take advantage of this orbital laboratory, engineers and scientists at the Wisconsin Center for Space Automation and Robotics (WCSAR), University of Wisconsin-Madison, developed a plant growth facility capable of supporting plant growth in the microgravity environment. Utilizing this Advanced Astroculture (ADVASC) plant growth facility, an experiment was conducted with the objective to grow Arabidopsis thaliana plants from seed-to-seed on the ISS. Dry Arabidopsis seeds were anchored in the root tray of the ADVASC growth chamber. These seeds were successfully germinated from May 10 until the end of June 2001. Arabidopsis plants grew and completed a full life cycle in microgravity. This experiment demonstrated that ADVASC is capable of providing environment conditions suitable for plant growth and development in microgravity. The normal progression through the life cycle, as well as the postflight morphometric analyses, demonstrate that Arabidopsis thaliana does not require the presence of gravity for growth and development.

Air Conditioning↗

Complement in renal transplantation.

Previous research and therapy in renal transplantation largely focused on the cellular arm of the adaptive immune response. Evidence is emerging that innate immune mechanisms, particularly complement, play a greater role in inflammatory and immune responses against the graft than has been previously recognized. Alternative complement pathway activation appears to mediate renal ischaemia/reperfusion injury, and proximal tubular cells may be both the source and the site of attack of complement components in this setting. Locally produced complement also plays a role in the development of both cellular and antibody-mediated immune responses against the graft. C4d staining has emerged as a useful marker of humoral rejection both in the acute and in the chronic setting and led to renewed interest in the significance of anti-donor antibody formation. A number of therapies are in development which inhibit complement or reduce local synthesis, and may lead to an improved clinical outcome following renal transplantation.

Complement C4↗

Multiple RNA splicing and the presence of cryptic RNA splice donor and acceptor sites may contribute to low expression levels and poor immunogenicity of potential DNA vaccines containing the env gene of equine infectious anemia virus (EIAV).

The env gene is an excellent candidate for inclusion in any DNA-based vaccine approach against equine infectious anemia virus (EIAV). Unfortunately, this gene is subjected to mutational pressure in E. coli resulting in the introduction of stop codons at the 5' terminus unless it is molecularly cloned using very-low-copy-number plasmid vectors. To overcome this problem, a mammalian expression vector was constructed based on the low-copy-number pLG338-30 plasmid. This permitted the production of full-length EIAV env gene clones (plcnCMVenv) from which low-level expression of the viral surface unit glycoprotein (gp90) was detected following transfection into COS-1 cells. Although this suggested the nuclear export of complete env mRNA moieties at least two additional polypeptides of 29 and 20kDa (probably Rev) were produced by alternative splicing events as demonstrated by the fact that their synthesis was prevented by mutational inactivation of EIAV env splice donor 3 (SD3) site. The plcnCMVenv did not stimulate immune responses in mice or in horses, whereas an env construct containing an inactivated SD3 site (plcnCMVDeltaSD3) did induce weak humoral responses against gp90 in mice. This poor immunogenicty in vivo was probably not related to the inherent antigenicity of the proteins encoded by these constructs but to some fundamental properties of EIAV env gene expression. Attempts to modify one of these properties by mutational inactivation of known viral RNA splice sites resulted in activation of previously unidentified cryptic SD and slice acceptor sites.

Amino Acid Sequence↗

ErbB-4: a receptor tyrosine kinase.

ErbB-4 is a receptor tyrosine kinase that is activated by the binding of specific growth factors to its ectodomain. In addition to the initiation of signal transduction pathways that direct cell responses, such as proliferation or differentiation, this receptor is subject to ligand-dependent trafficking events. The signal transduction events are controlled by ligand-dependent activation of the receptor tyrosine kinase activity, which results in receptor autophosphorylation and the tyrosine phosphorylation of other cellular proteins. The trafficking events include migration into and out of membrane microdomains, entry into internalization pathways and endocytosis, plus proteolytic fragmentation.

Amino Acid Sequence↗

Hormesis: the new approach in risk assessment?

Hormesis is a dose-response phenomenon characterized by either a U-shaped or an inverted U-shaped dose response depending on the different end points measured. In a paper in this issue of the journal, Drs Jayjock and Lewis advocate for the application of hormesis in the field of industrial hygiene, and suggest the use of hormesis as a default assumption in the risk assessment process. However, there are many difficulties for the utilization of hormesis in the field of industrial hygiene. Indeed, it is impossible to test the hormesis hypothesis in many commonly employed experimental model systems for end points of public health concern, and the mechanism of low-dose stimulation of hormesis is not clear. Even if hormesis were proven biologically, its assessment is limited due to difficulties of study design, biological markers selection, statistical power considerations, model and end point selection, and risk model approaches.

Animals↗