[Total environment protection for moderate and severe grade of acute radiation sickness].
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Biomedical subjects
Publications and source records attributed to X B Wang.
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It is well known that the conventional dielectrophoretic force acting on a polarised particle in a non-uniform AC electric field is proportional to the in-phase component of the induced dipole moment and the non-uniformity of the field strength. In contrast, the travelling-wave-dielectrophoretic force that acts on a particle subjected to a travelling electric field is proportional to the out-of-phase component of the induced dipole moment. We derive a theory that unifies the description and interpretation of conventional dielectrophoretic and travelling-wave-dielectrophoretic forces. We show that a particle in a non-uniform AC electric field experiences a dielectrophoretic force due to spatial non-uniformities of the magnitude and the phase of the field interacting, respectively, with the in-phase and out-of-phase components of the induced dipole moment. The theory is used to explain the translational effects observed for particles in the presence of standing, travelling and rotating fields in several experimental electrode configurations. The good agreement found between the experimental observations and the theoretical predictions validate the theory.
Electrorotation measurements were used to demonstrate that the dielectric properties of the metastatic human breast cancer cell line MDA231 were significantly different from those of erythrocytes and T lymphocytes. These dielectric differences were exploited to separate the cancer cells from normal blood cells by appropriately balancing the hydrodynamic and dielectrophoretic forces acting on the cells within a dielectric affinity column containing a microelectrode array. The operational criteria for successful particle separation in such a column are analyzed and our findings indicate that the dielectric affinity technique may prove useful in a wide variety of cell separation and characterization applications.
Recent studies have suggested that opiate addiction is associated with transcriptional changes. We developed a novel method, in situ DNA-protein binding (ISDB), for investigating the distribution and changes of DNA binding activity of transcription factors in the brain. Using this method, we found that cAMP response element (CRE) binding activity was decreased by chronic morphine treatment in specific regions including the amygdala complex, thalamus, cerebral cortex and hypothalamus in mouse brain. This effect persisted for at least 14 days after the cessation of morphine. These data suggest that chronic morphine treatment elicits a long-term change in cAMP-mediated gene expression in the brain.
Electrorotation (ROT) spectra of Friend murine erythroleukaemia DS19 cells were measured in the frequency range 10 kHz-100 MHz as a function of suspension osmolality and cell differentiation treatment with hexamethylene bisacetamide (HMBA). A minimization program was employed to curve-fit the measured spectra using a single-shell dielectric model, allowing the derivation of cellular interior conductivity and permittivity (valid for the frequency range 10-100 MHz) and the cytoplasmic membrane capacitance (its dependence on the cell differentiation state and suspension osmolality having been reported earlier). Following HMBA treatment, DS19 cells exhibited a slight increment in average interior permittivity and a decrement in interior conductivity, although the changes were not statistically significant. For both untreated and HMBA treated samples, the average interior conductivity increased and permittivity decreased with increasing suspension osmolality. Of significance was that the average permittivity of cell interiors was larger than that of pure water. The electrorotation spectra of freshly prepared cell nuclei were measured, and the derived nuclear dielectric parameters were employed in numerical simulations to investigate the effects of nuclei on the ROT spectra of intact cells. Other cellular internal structures such as mitochondria were also analysed using theoretical simulations. It was concluded that the derived large permittivity values did not result from cell nuclei or mitochondria, and, instead, we suggest that they may arise from the combined effects of several cytoplasmic organelles.
We used electrorotation measurements to investigate alterations in the plasma membranes of DS19 murine erythroleukaemia cells that accompanied erythropoietic differentiation induced by hexamethylene bisacetamide (HMBA). Following 3 days of HMBA treatment, the mean cell membrane specific capacitance determined from electrorotation spectra of individual, viable cells at physiological tonicity (300 mosmol/kg) fell from 1.74 to 1.53 microF/cm2, in agreement with trends observed earlier by dielectrophoretic measurements on bulk cell populations. Scanning and transmission electron microscopy revealed that the relatively high values found for cell membrane capacitance (> 1 microF/cm2) reflected the large area of plasma membrane associated with complex surface morphology including numerous microvilli. Furthermore, it demonstrated that the fall in membrane capacitance during HMBA treatment correlated with a reduction in the density of these complex surface features. Differences in the mechanical characteristics of the cell membranes of untreated and treated cells were then examined by exposing cells to osmotic stress. The intricacy of membrane morphology intensified with increasing osmolality of the suspending medium and this was reflected in higher specific capacitance values. When the osmolality was increased from 210 to 450 mosmol/kg, the mean membrane capacitance of untreated DS19 cells changed from 1.58 to 2.05 microF/cm2 while that for HMBA-treated cells changed from 1.47 to 1.72 microF/cm2, a significantly smaller response. This demonstrated that cells exposed to 72 h of differentiation treatment had an enhanced mechanical resilience as compared with their untreated counterparts, evidencing the early stages of the development of the membrane skeleton which becomes fully developed in mature erythrocytes. Our findings demonstrate the value of electrorotation measurements as a method for the non-invasive characterisation of viable leukaemic cells and their responses to stimuli and show that the membrane capacitance values so derived reflect membrane morphology.
The development of opiate tolerance and dependence are thought to be associated with gene expression. Our previous studies have shown that the binding activity of nuclear factors to a single-stranded oligo-DNA containing cAMP response element (ssCRE) is altered by long term treatment with morphine in cultured neuronal cells. In the present experiments, the effects of acute and chronic treatments with morphine on the binding of nuclear proteins to single- and double-stranded oligo-DNAs of the cAMP response element were studied in the mouse brains by using gel shift assay. The activity of single-stranded CRE binding proteins (ssCRE-BP) was decreased by chronic morphine treatment to about 40% of control in the cerebellum. The effect of chronic morphine treatment on the binding activity persisted for at least 2 weeks after morphine withdrawal. The activity of double-stranded CRE binding proteins was also detected in the cerebellum, but it was insensitive to the morphine treatment. The activity of ssCRE-BP was also decreased by acute morphine treatment in 5 h, but it returned to control level in 24 h. These data suggest that the change of ssCRE-BP can be involved in the development of tolerance and dependence.
The development of drug tolerance and dependence are thought to be associated with gene expression. Our studies showed that the binding activity of nuclear factors to several DNA sequences is altered by long-term treatment with methamphetamine, cocaine and morphine: 1) the binding activity of AP-1 increased markedly in the mouse brain after administration of methamphetamine and cocaine, 2) CRE-binding activity was decreased by chronic morphine treatment in the amygdala complex, cerebral cortex and hypothalamus of the mouse brain, and 3) the binding activity of single-stranded CRE binding proteins was decreased by chronic morphine treatment in the mouse cerebellum. These data suggest that the changes of DNA binding proteins can be involved in the development of drug tolerance and dependence.
Receptor-mediated changes in intracellular Ca2+ in ileal longitudinal smooth muscles of guinea pig were studied. Stimulation of muscarinic receptors by carbachol induced both Ca(2+)-influx through plasma membranes and Ca(2+)-release from intracellular stores. Pretreatment of the muscle with an inhibitor of phospholipase A2 abolished the Ca2+ influx but not the Ca(2+)-release, whereas an inhibitor of phospholipase C showed opposite effects. The inhibitors of cyclooxygenase and lipoxygenase enhanced the muscarinic receptor-induced Ca(2+)-influx. Addition of arachidonic acid mimic the receptor-induced Ca(2+)-influx. Treatment of muscles with pertussis toxin abolished the receptor-induced release of arachidonic acid as well as Ca(2+)-influx, but was less effective on the IP3 formation and the Ca(2+)-release. Taken together, our results suggest that phospholipase A2 but not phospholipase C pathway is involved in the muscarinic receptor-induced Ca(2+)-influx in ileal smooth muscle.
A micronutrient-fortified rusk for weanling children was tested in a rural area near Beijing. Two hundred twenty-six children aged 6-13 mo were randomly assigned by village to either a micronutrient-fortified or an unfortified rusk, daily for 3 mo. The fortified rusk contained extra zinc; iron; calcium; vitamins A, D, and B-12; thiamin, riboflavin, niacin, and folic acid. Infants receiving the fortified rusk exhibited no decline in hemoglobin concentrations during the study whereas those receiving the unfortified rusk exhibited a significant decline. Improvements were also seen in erythrocyte porphyrin, plasma vitamin A, and riboflavin status, but these improvements were seen in both of the groups. Micronutrient fortification was probably beneficial for iron status and the fortified rusk promises to be an effective vehicle for supplementation.
A novel method, in situ DNA-protein binding (in situ DPB), was developed to detect the distribution and DNA-binding activity of AP-1 and Sp1 binding proteins in situ. The regional distribution of AP-1 binding protein in mouse brain was different from that of Sp1. Antibody against the DNA-binding domain of Jun protein markedly reduced the AP-1 but not the Sp1 binding activity. The binding activity of AP-1 probe increased markedly in the brain after administration of methamphetamine. These results suggest that the in situ DPB is convenient and sensitive for detecting the distribution and the DNA-binding activity of transcription factors in situ.
Medium hyperosmolarity between 300 (normal medium osmolarity) and 600 mOsm inhibited in a concentration-correlated fashion (r greater than 0.97, p less than 0.001) the rise in intracellular Ca2+ concentration ([Ca2+]i) and prolactin (PRL) secretion induced in GH4C1 cells by depolarizing 30 mM K+. [Ca2+]i concentration and PRL secretion were tightly related between 300 and 600 mOsm (r = 0.976, p less than 0.001); 50% inhibition of both occurred at 450 mOsm. Medium hyperosmolarity slowed the rate of Ca2+ influx. At 600 mOsm the rise in both [Ca2+]i and PRL secretion was abolished but PRL secretion induced by 1 microM phorbol 12-myristate 13-acetate was not significantly reduced. Our data suggest that inhibition of Ca2+ influx may be the primary mechanism by which extracellular hyperosmolarity inhibits PRL secretion induced by high medium K+ in GH4C1 cells. Depression of the Ca2+ intracellular transduction system may play a pathophysiological role in vivo in conditions such as dehydration and hypertonic coma.
An electrode system is described for the near-simultaneous application and measurement of translational, levitational and rotational forces induced by AC electric fields, and this has been used to investigate the differences in the AC electrodynamics of viable and non-viable yeast cells. A new approach to the theoretical modelling of the experimental data has enabled these differences to be quantified in terms of changes in the conductivity of the cytoplasmic membrane and cell interior. The results are considered to have potentially important biomedical and biotechnological applications.
In skeletal muscles, calcitonin gene-related peptide (CGRP) released from motor nerve terminals and humoral catecholamines stimulate adenylate cyclase (AC) and enhance muscle contraction. The effects of denervation and treatment with reserpine on twitch contraction and the AC system in rat diaphragm were investigated. The basal levels of twitch contraction and AC activity of the diaphragm of rats were both increased 2 weeks after phrenic nerve denervation but were not altered by treatment with reserpine. Reserpine treatment provoked supersensitivity of AC to isoproterenol, without affecting the response to CGRP. On the other hand, denervation decreased the activation of AC and enhancement of twitch contraction by CGRP, without affecting the responses to isoproterenol. These data suggest that denervation causes up-regulation of AC as a result of loss of CGRP release from nerve terminal and that depletion of catecholamines by reserpine treatment supersensitizes the responses at the beta-adrenoceptor level. Thus, nervous and humoral factors regulate the AC system in striated muscle by different mechanisms.
Muscarinic receptor-mediated elevations in intracellular Ca2+ concentration ([Ca2+]i) in the longitudinal smooth muscle of guinea pig ileum were studied by the use of fura-2 fluorescence. Dose-response analysis indicated a difference in the potencies of carbachol (CCh) to increase [Ca2+]i in the presence and absence of extracellular Ca2+. For the increase in [Ca2+]i due to Ca2+ release from intracellular stores in the absence of extracellular Ca2+, the ED50 value of CCh was 3 x 10(-5) M. On the other hand, in the presence of Ca2+, the ED50 value was 2.5 x 10(-7) M, indicating that a low concentration of CCh (less than 10(-7) M) caused influx of extracellular Ca2+ without Ca2+ release. Oxotremorine and pilocarpine induced Ca2+ influx, but were less potent inducers of Ca2+ release. CCh also stimulated the formation of inositol trisphosphates (IP3) with an ED50 value of (4.5 x 10(-5) M), which was similar to that for Ca2+ release from intracellular stores. Treatment of the smooth muscle with neomycin (1 mM), a phospholipase C inhibitor, abolished both CCh-induced IP3 formation and Ca2+ release from intracellular stores, but did not affect CCh-induced Ca2+ influx. These results suggest that the pathway for muscarinic stimulation of Ca2+ influx through plasma membranes is different from that for Ca2+ release from intracellular stores, which seems to be coupled with IP3 formation.
To evaluate the clinical efficacy of 99Tcm-MIBI myocardial tomography for detecting coronary artery disease (CAD) 115 consecutive patients who underwent both 99Tcm-MIBI single photon emission computed tomography (SPECT) and coronary arteriography were studied. Thirty-three patients without and 82 with significant coronary artery disease were documented by coronary arteriography. The overall sensitivity and specificity of 99Tcm-MIBI SPECT for detecting coronary artery disease were 96 and 87.9%, respectively. The sensitivity for identifying patients with CAD without myocardial infarction was 88%. The sensitivity of 99Tcm-MIBI SPECT for detecting individual coronary artery lesions was 86% for left anterior descending artery (LAD), 69% for left circumflex artery (Lcx) and 86% for right coronary artery (RCA), lesions respectively. In conclusion, 99Tcm-MIBI SPECT provides a reliable method for detecting CAD.
The relations among race, family income, and low birth weight were examined using information obtained from the National Longitudinal Survey of Youth, which conducted yearly interviews with a nationally representative sample of young women identified in the late 1970s. Data were available for these women and their offspring from 1979 through 1988. Maternal education, maternal age, age/parity risk, marital status, and smoking during pregnancy served as covariates in cross-sectional and longitudinal analyses. The risk of low birth weight among births to black women and white women who were poor was at similarly high levels regardless of whether poverty was determined prior to study entrance or during the study period. Longitudinal analyses showed an exceptionally large increase in risk of low birth weight among children born to women whose prior pregnancy ended in a low-birth-weight infant. These two findings emphasize the importance of factors antecedent to the pregnancy in the genesis of low birth weight.
Tetraethylammonium (TEA), a K+ channel blocker, induced prolactin (PRL) secretion in GH4C1 cells in a dose-dependent manner when applied at a concentration from 1-20 mM. During continuous exposure to TEA, a significant increase in PRL secretion occurred by 20 min and the response was sustained until the end of a 60-min exposure. Blocking Ca2+ influx by employing a Ca(2+)-depleted medium or the Ca2+ channel blocker, nifedipine, prevented induction of PRL secretion by 20 mM TEA. Preincubation of the cells for 10 min with 20 mM TEA did not inhibit PRL secretion induced by thyrotropin-releasing hormone (TRH), phorbol 12-myristate 13-acetate (TPA) or by cell swelling produced by 30% medium hyposmolarity, but significantly depressed that induced by depolarizing 30 mM K+. BaCl2, another K+ channel blocker, had the same effect on PRL secretion as TEA. The data suggest that blocking K+ channels may cause membrane depolarization, thereby inducing Ca2+ influx which is a potent stimulus for PRL secretion in GH4C1 cells.