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Biomedical subjects

W Zhao

Publications and source records attributed to W Zhao.

At least 235 records · Page 13Linked to original sources

Posttraumatic cerebral ischemia after fluid percussion brain injury: an autoradiographic and histopathological study in rats.

OBJECTIVES: Mild-to-moderate reductions in local cerebral blood flow (ICBF) have been reported to occur in rats after moderate (1.7-2.2 atm) fluid percussion brain injury. The purpose of this study was to determine whether evidence for severe ischemia (i.e., mean ICBF < 0.25 ml/g/min) could be demonstrated after severe brain injury. In addition, patterns of indium-labeled platelet accumulation and histopathological outcome were correlated with the hemodynamic alterations. METHODS: Sprague-Dawley rats (n = 23), anesthetized with halothane and maintained on a 70:30 mixture of nitrous oxide:oxygen and 0.5% halothane, underwent normothermic (37 degrees C) parasagittal fluid percussion brain injury (2.4-2.6 atm). Indium-111-tropolone-labeled platelets were injected 30 minutes before traumatic brain injury (TBI), while 14C-iodoantipyrine was infused 30 minutes after trauma for ICBF determination. Sham-operated animals (n = 8) underwent similar surgical procedures but were not injured. For histopathological analysis, traumatized rats (n = 5) were perfusion-fixed 3 days after TBI. RESULTS: In autoradiographic images of indium-labeled platelets, abnormal platelet accumulation that was most pronounced overlying the pial surface was commonly associated with severe reductions in ICBF within underlying cortical regions 30 minutes after TBI. For example, within the lateral parietal cortex, ICBF was significantly reduced from 1.67 +/- 0.11 ml/g per minute (mean +/- standard error of the mean) in sham-operated animals to 0.23 +/- 0.03 ml/g per minute within the traumatized group. In addition to focal severe ischemia, moderate reductions in ICBF were detected throughout the traumatized hemisphere, including the frontal and occipital cortices, hippocampus, thalamus, and striatum. Mild decreases in ICBF were also observed throughout the contralateral cerebral cortex. At 3 days after severe TBI, histopathology demonstrated intracerebral and subarachnoid hemorrhage associated with cerebral contusion and selective neuronal necrosis. CONCLUSION: These data indicate that multiple cerebrovascular abnormalities, including subarachnoid hemorrhage, focal platelet accumulation, and severe ischemia, are important early events in the pathogenesis of cortical contusion formation after TBI. Injury severity is expected to be a critical factor in determining what therapeutic strategies are attempted in the clinical setting.

Animals↗

Digital radiology using active matrix readout of amorphous selenium: detectors with high voltage protection.

A flat-panel x-ray imaging detector is being investigated for digital radiography and fluoroscopy. The detector uses a layer of amorphous selenium (a-Se) to convert x rays to a charge image, which is then electronically read out with a two-dimensional array of thin film transistors (TFTs). In order to sensitize the a-Se layer to x rays, a high voltage (of the order of several thousand volts) is applied to its top surface. The TFTs, which are at the bottom surface of the a-Se layer, are not subjected to any high voltage under normal radiological operational conditions since the pixel potential is < 10 V. However under a fault condition where these two events occur simultaneously: (1) suspended detector scan; and (2) an x-ray exposure more than ten times higher than normal, the voltage on the TFTs could rise to a damaging value. This paper describes a method for protecting the TFTs from high voltage damage under this fault condition. It employs a dual-gate TFT structure, one gate is for scanning control and the other is connected to the pixel electrode for high voltage protection. Before the pixel potential reaches a damaging value, the protection gate turns on the TFT automatically and drains excess charge away from the pixel thus providing a safe pixel saturation potential. In this paper, the characteristic curves of dual-gate TFTs are studied both theoretically and experimentally. The pixel x-ray response for imaging detectors with high voltage protection are predicted, and it is shown that with practical TFT designs the detector can provide a safe pixel saturation potential as well as satisfy the dynamic range required for diagnostic x-ray imaging applications.

Equipment Design↗

Digital radiology using active matrix readout of amorphous selenium: radiation hardness of cadmium selenide thin film transistors.

A flat-panel x-ray imaging detector using active matrix readout of amorphous selenium (a-Se) is being investigated for digital radiography and fluoroscopy. The active matrix consists of a two-dimensional array of thin film transistors (TFTs). Radiation penetrating through the a-Se layer will interact with the TFTs and it is important to ensure that radiation induced changes will not affect the operation of the x-ray imaging detector. The methodology of the present work is to investigate the effects of radiation on the characteristic curves of the TFTs using individual TFT samples made with cadmium selenide (CdSe) semiconductor. Four characteristic parameters, i.e., threshold voltage, subthreshold swing, field effect mobility, and leakage current, were examined. This choice of parameters was based on the well established radiation damage mechanisms for crystalline silicon metal-oxide-semiconductor field-effect transistors (MOSFETs), which have a similar principle of operation as CdSe TFTs. It was found that radiation had no measurable effect on the leakage current and the field effect mobility. However, radiation shifted the threshold voltage and increased the subthreshold swing. But even the estimated lifetime dose (50 Gy) of a diagnostic radiation detector will not affect the normal operation of an active matrix x-ray detector made with CdSe TFTs. The mechanisms of the effects of radiation will be discussed and compared with those for MOSFETs and hydrogenated amorphous silicon (a-Si:H) TFTs.

Cadmium Compounds↗

Digital radiology using active matrix readout of amorphous selenium: geometrical and effective fill factors.

Flat panel self-scanned x-ray detectors using amorphous selenium (a-Se) as the photoconductor are being developed to replace both film/screen cassette systems for radiography and image intensifier (XRII)/video systems for fluoroscopy. These use a two-dimensional array of pixel electrodes to collect and readout the latent image charges formed on the photoconductor surface. The percentage of the area covered by the pixel electrodes (i.e., the geometrical fill factor fg) is always less than unity. In this paper, a novel approach is introduced to make the charge collection by pixel electrodes almost complete (i.e., a close to unity effective fill factor). The idea is to bend the electric field lines in the a-Se layer in such a way that image charges cannot land in the gap region between electrodes. This is achieved by depositing holes in the gap region, which is possible because there are charge traps available at the a-Se/insulator interface. The distribution of holes required in the gap region is calculated. Various factors associated with the feasibility of this approach as well as a method to deposit these holes are discussed. Application of the approach to the case of mammography is also included.

Biophysical Phenomena↗

Digital x-ray imaging using amorphous selenium: reduction of aliasing.

Alias reduction is analyzed with the concept of an equivalent presampling filter, and a mathematical approach is established to find the equivalent presampling filter corresponding to specific digital image processing algorithms. The effects of different sampling period T and sampling aperture tau on aliasing artifacts and on the resultant detective quantum efficiency (DQE) for a self-scanned, flat-panel, amorphous selenium detector are obtained. Different effective apertures can be obtained from the same detector by averaging signals over adjacent pixels. It is shown that adding outputs from M adjacent pixels is equivalent to introducing an equivalent presampling filter with special properties. Appropriate selection of the averaging parameters (M and weights) is shown to reduce the aliasing artifact in the resultant image. The effect of incomplete charge collection due to geometrical effects (fill factor) is examined. It is shown that a large fill factor is desirable for aliasing reduction. The relationship between a digital filter applied to the sampled signal and its equivalent presampling analog filter is also established. Analytical formulas for the sampled spectrum of white signal and for the sampled power spectrum of white noise are obtained for aperture functions with a spatially uniform response. These formulas take into accounts aliasing artifacts, signal correlation and aperture function response, and demonstrate the dependence of sampled spectra on T and tau. With these formulas the detective quantum efficiency DQE is derived. It is shown that the resultant DQE depends only on the fill factor and the size of readout electrode tau 0, but is completely independent of the degree or type of pixel averaging. That is, even though the pixel averaging method reduces aliasing it leaves DQE (omega) unchanged. When significant amplifier noise is present the DQE obtained with the pixel averaging method can be better than those obtained with an analog presampling filter. Finally, it is pointed out that the requirement of reducing aliasing artifacts conflicts with other requirements for a detector such as maximizing modulation transfer function (MTF). A careful and practical compromise has to be made by a detector designer in choosing the extent to which the aliasing artifacts are eliminated.

Algorithms↗

Regional differences in the cellular immune response to experimental cutaneous or visceral infection with Leishmania donovani.

Infection with the protozoan Leishmania donovani can cause serious visceral disease or subclinical infection in humans. To better understand the pathogenesis of this dichotomy, we have investigated the host cellular immune response to cutaneous or visceral infection in a murine model. Mice infected in the skin developed no detectable visceral parasitism, whereas intravenous inoculation resulted in hepatosplenomegaly and an increasing visceral parasite burden. Spleen cells from mice with locally controlled cutaneous infection showed strong parasite-specific proliferative and gamma interferon (IFN-gamma) responses, but spleen cells from systemically infected mice were unresponsive to parasite antigens. The in situ expression of IFN-gamma, interleukin-4 (IL-4), IL-10, IL-12, and inducible nitric oxide synthase (iNOS) mRNAs was determined in the spleen, draining lymph node (LN), and cutaneous site of inoculation. There was considerably greater expression of IFN-gamma and IL-12 p40 mRNAs in the LN draining a locally controlled cutaneous infection than in the spleen following systemic infection. Similarly, there was a high level of IFN-gamma production by LN cells following subcutaneous infection but no IFN-gamma production by spleen cells following systemic infection. Splenic IL-4 expression was transiently increased early after systemic infection, but splenic IL-10 transcripts increased throughout the course of visceral infection. IL-4 and IL-10 mRNAs were also increased in the LN following cutaneous infection. iNOS mRNA was detected earlier in the LN draining a cutaneous site of infection compared to the spleen following systemic challenge. Thus, locally controlled cutaneous infection was associated with antigen-specific spleen cell responsiveness and markedly increased levels of IFN-gamma, IL-12, and iNOS mRNA in the draining LN. Progressive splenic parasitism was associated with an early IL-4 response, markedly increased IL-10 but minimal IL-12 expression, and delayed expression of iNOS.

Animals↗

Deregulation of poly(A) polymerase interferes with cell growth.

Vertebrate poly(A) polymerase (PAP) contains a catalytic domain and a C-terminal Ser-Thr-rich regulatory region. Consensus and nonconsensus cyclin-dependent kinase (cdk) sites are conserved in the Ser-Thr-rich region in vertebrate PAPs. PAP is phosphorylated by cdc2-cyclin B on these sites in vitro and in vivo and is inactivated by hyperphosphorylation in M-phase cells, when cdc2-cyclin B is active. In the experiments described here, we undertook a genetic approach in chicken DT40 cells to study the function of PAP phosphorylation. We found that PAP is highly conserved in chicken and is essential in DT40 cells. While cells could tolerate reduced levels of PAP, even modest overexpression of either wild-type PAP or a mutant PAP with two consensus cdk sites mutated (cdk- PAP) was highly deleterious and at a minimum resulted in reduced growth rates. Importantly, cells that expressed cdk- PAP had a significantly lower growth rate than did cells that expressed similar levels of wild-type PAP, which was reflected in increased accumulation of cells in the G0-G1 phase of the cell cycle. We propose that the lower growth rate is due to the failure of hyperphosphorylation and thus M-phase inactivation of cdk- PAP.

Amino Acid Sequence↗

Diffusion-weighted magnetic resonance imaging confirms marked neuroprotective efficacy of albumin therapy in focal cerebral ischemia.

BACKGROUND AND PURPOSE: We have recently shown high-dose human serum albumin therapy to confer marked histological protection in experimental middle cerebral artery occlusion (MCAo). We have now used diffusion-weighted magnetic resonance imaging (DWI) in conjunction with morphological methods to expand our understanding of this therapeutic approach. METHODS: Physiologically controlled Sprague-Dawley rats received 2-hour MCAo by the modified intraluminal suture method. Treated rats received 25% human serum albumin solution (1% by body weight) immediately after the MCA was reopened. Vehicle-treated rats received saline. Computer-based image averaging was used to analyze DWI data obtained 24 hours after MCAo and light-microscopic histopathology obtained at 3 days. In a matched series, plasma osmolality and colloid oncotic pressure, as well as brain water content, were determined. RESULTS: Albumin therapy, which lowered the hematocrit on average by 37% and raised plasma colloid oncotic pressure by 56%, improved the neurological score throughout the 3-day survival period. Within the ischemic focus, the apparent diffusion coefficient (ADC) computed from DWI data declined by 40% in vehicle-treated rats but was preserved at near-normal levels (8% decline) in albumin-treated rats (P<0.001). Albumin also led to higher ADC values within unlesioned brain regions. Histology revealed large consistent cortical and subcortical infarcts in vehicle-treated rats, while albumin therapy reduced infarct volume at these sites, on average, by 84% and 33%, respectively. Total infarct volume was reduced by 66% and brain swelling was virtually eliminated by albumin treatment. Microscopically, while infarcted regions of vehicle-treated rats had the typical changes of pannecrosis, infarcted zones of albumin-treated brains showed persistence of vascular endothelium and prominent microglial activation, suggesting that albumin therapy may help to preserve the neuropil within zones of residual infarction. CONCLUSIONS: These findings confirm the striking neuroprotective efficacy of albumin therapy in focal cerebral ischemia and reveal that this effect is associated with DWI normalization and a mitigation of pannecrotic changes within zones of residual injury.

Animals↗

Neuroendocrine and reproductive functions in male mice with targeted disruption of the prolactin gene.

Mice with a targeted disruption (knock-out) of the PRL gene (PRL-KO) were used to study the physiological role of PRL in the control of male neuroendocrine functions related to reproduction. Compared with normal males, PRL-KO mice had significant reductions in median eminence dopamine content, plasma LH levels, LH and FSH secretion in vitro (per mg pituitary), and weights of seminal vesicles and ventral prostate. PRL was not detectable in incubation medium with pituitaries from PRL-KO mice. No alterations were detected in PRL-KO mice in median eminence norepinephrine, plasma testosterone levels, or testosterone release (per mg testis) in vitro with or without LH. No differences were detected in PRL-KO vs. normal male mice in the interval from housing with normal female mice until conception, rate of pregnancy, or the number of live pups per litter. Pituitary weight in PRL-KO mice was increased (1.78 +/- 0.22 vs. 3.35 +/- 0.20 mg; P < 0.001), presumably due to reduced feedback inhibition and hypertrophy and/or hyperplasia of nonfunctional lactotrophs. These results indicate that the absence of PRL reduces pituitary LH release, attenuates median eminence dopaminergic activity, and affects the growth of seminal vesicles and ventral prostate. Although it was previously shown that PRL can repair the reproductive defect in male pituitary dwarf mice, our current results imply that the PRL deficiency alone is not sufficient to cause male infertility, although there are obvious alterations in reproductive neuroendocrine function in PRL-KO males.

Animals↗

Long-term Effects of Various Iodine and Fluorine Doses on the Thyroid and Fluorosis in Mice.

OBJECTIVE: To elucidate the participation of the independent and combined long term effect of various concentrations of iodine and fluorine on the pathogenesis of goiter and fluorosis in mice. METHODS: Nine drinking water supplies with different iodine and fluorine content were prepared by combination of potassium iodate and sodium fluoride solutions in bidistilled water. The concentrations of iodide were: 1. iodine deficiency (ID): 0.0; 2. iodine normal (IN): 20.0; 3. iodine excess (IE) 2500.0 ug/l; and these of fluoride were: 1. fluoride deficiency (FD) 0.0; 2. fluoride normal 0.6; 3. fluoride excess (FE), 30.0 mg/l. A total of 288 Kunmim mice was divided into 9 groups consisting of 32 animals each and each group, in addition to basal diet, received one of following iodide/fluoride mixtures: ID+FD, ID+FN, ID+FE, IN+FD, IN+FN, IN+FE, IE+FD, IE+FN, IE+FE. By such manner, one half of the animals of each group was treated for 100 days and the other half for 150 days. RESULTS: It was found that ID only and IE only could both induce the goiter. FE induced dental fluorosis and increased fluorine content in the bone. In addition, fluorine also affected the thyroid changes induced by ID or IE. After 100 days of treatment, fluorine showed some stimulatory effect on the thyroid in ID conditions and inhibitory effect in IE conditions. After 150 days, however, the effects of fluorine on the thyroid reversed as compared with that of 100 days. On the other hand, difference of iodide intake could also increase the toxic effects of FE on the incisors and bones. The rate and degree of the incisor fluorosis, the fluorine contents in the bone were significantly higher in the ID+FE group than those in the IN+FE and IE+FE groups. CONCLUSIONS: Both iodine deficiency and excess induced goiter as well as other functional and histopathological changes in the mouse thyroid. Excessive fluorine caused fluorosis of incisors and limb bones. In addition, iodine and fluorine do have mutually interacting effects on both goiter and fluorosis in the experimental mice.

Journal Article↗

[Relationship between clinical manifestation and pathology in pediatric renal diseases].

To elevate the clinical diagnosis and pathological compatibility of pediatric kidney diseases. Pathological changes from 101 cases of pediatric renal diseases were studied, covering 13 diseases entities, including glomerulo-nephritis, simple nephrotic syndrome, nephritic nephrotic syndrome etc. The technique of tru-cut biopsy under the guidance of B ultrasonogram was used in renal biopsy. The renal puncture biopsy was 100% satisfactory. Pathological changes involved 12 pathological types. MsPGN were the most commonly seen (39.6%), followed by MPGN and ICPGN (12.87% and 10.89%) respectively. It was found that children with similar clinical manifestation may possess different pathological changes, while the same pathological entity may present multiple clinical manifestation. The results suggest that renal biopsy pathological diagnosis is important in the diagnosis, treatment and prediction of prognosis in pediatric renal disease.

Adolescent↗

[Tissue factor expression during all-trans retinoic acid or arsenic trioxide treatment in acute promyelocytic leukemia].

OBJECTIVE: In order to study the effect of all-trans retinoic acid (ATRA) or arsenic trioxide (As2O3) treatment on the expression of tissue factor (TF) in acute promyelocytic leukemia(APL). METHODS: The plasma level of soluble fibrin monomer complex(SFMC) and D-dimer(D-D), and the TF level of cell lysate were measured by ELISA, the transcription of TF mRNA was assessed by RT-PCR. RESULTS: The plasma level of SFMC and D-D, the procoagulant activity(PCA) of bone marrow blasts, the TF level of cell lysate and the transcription of TF mRNA all remarkably elevated at diagnosis, while reduced after ATRA or As2O3 therapy. CONCLUSION: Both ATRA and As2O3 downregulated the expression of TF mRNA, decreased the PCA and TF levels in APL cells, inhibited coagulation activation and secondary hyperfibrinolysis, thus greatly relieved the bleeding symptom in the early stage of treatment.

Adolescent↗

Influence of simulated microgravity environmental factor on ginseng cell growth and ginseng saponin content.

When ginseng (Panax ginseng C.A. Meyer) cells were subjected horizontal rotation on a clinostat, their growth and ginseng saponin content differed from those cultured in normal gravitational environments (control). Both fresh and dry weights of ginseng cells rotating on clinostat were higher than those of the control, and the difference in dry weight was particularly obvious. After 3 weeks of cultivation, saponin content in ginseng was 10% higher under the horizontal rotation treatment on the clinostat than that of the control. When ginseng cells were cultured on Ca2(+)-deprived medium and clinostatted for 3 weeks, their ginseng saponin content was almost twice of that of the control. Besides, in our experiments, the higher the Ca2+ concentration in medium, the lower the ginseng saponin content in the ginseng cells cultured.

Biomass↗

[Identification of gravity-related esterases (grEST1 and grEST2) in carrot callus cells].

A horizontal clinostat which mimics the microgravity in space was used to study its effects on carrot cells. After using boric acid buffer (pH 8.8) as extraction medium, PAGE pattern of esterase isozymes of carrot callus cells displayed 8 bands of which the activities of only 2 were affected by microgravity. They were named grEST1 and grEST2, where grEST stands for gravity-related esterase. The rates of increase in activity of them in carrot cells when cultured on a rotating horizontal clinostat were lower than that cultured in normal gravitational environments, and the difference increased with the culture time. The activities of grEST1 and grEST2 in carrot callus cells subjected to horizontal rotation were found to return to their original levels after being placed under normal gravity (1 x g) for 7 days. We suggest that the effect of simulated microgravity conditions on grEST1 and grEST2 activities in carrot callus cells is through affecting their synthesis. In addition, the activities of grEST1 and grEST2 were not inhibited by eserine, acetylcholine iodide, diisopropyl fluorophosphate and p-chloromercuribenzoate, which indicates that they are acetylesterases.

Acetylcholine↗

[Chemical research on stilbenes from Veratrum macckii Reg].

OBJECTIVE: To study the components in rhizome of Veratrum macckii. METHODS: Column chromatography and preparative thin layer chromatography with silica gel were employed for the isolation and purification of constituents. The structures were elucidated by IR, MS and 1H-NMR analysis. RESULTS: Two compounds were obtained and elucidated as resveratrol and 2,3',4,5'-tetrahydroxystilbene. CONCLUSION: The two compounds were separated from V. macckii for the first time.

Drugs, Chinese Herbal↗

[Observation on trachea inner walls of six species of Sect. Stenophora by scanning electronic microscope].

OBJECTIVE: To probe and identify the ultramicro characteristics of trachea inner walls(TIW) of six species of Sect. Stenophora, i.e., Rhizoma Dioscoreae Spongiosae, Rhizoma Dioscoreae Hypoglaucae, Rhizoma Dioscoreae Futschauensis, Rhizoma Dioscoreae Gracillimae, Rhizoma Dioscoreae Tokoro and Rhizoma Dioscoreae Zingiberensis, by scanning electron microscope (SEM). METHOD: The vertical microscopical sections are stuck on the platform of species and metal plated. TIW were observed and photographed by SEM. RESULT: The ultramicro characteristics of TIW, i.e., the smoothnesss of TIW, the existence of separation bands, the density, arrangement types, shapes and sizes of pits, etc., can be seen clearly under SEM. Further, there exist differences in the ultramicro characteristics of each species. CONCLUSION: The above six species of crude drugs can be identified according to their ultramicro characteristics of TIW. SEM can be used to study the ultramicro characteristics of crude drug rhizomas thus creating a new area for identifying crude drugs.

Magnoliopsida↗