Biomedical subjects

W Zhao

Publications and source records attributed to W Zhao.

At least 253 records · Page 14Linked to original sources

PubMed1998

[Protective effect of hyperin against cerebral ischemia-reperfusion injury].

The protective effect of hyperin (Hyp) against cerebral ischemia-reperfusion injury was studied. On the cerebral ischemia-reperfusion model in mice, Hyp (50, 100 mg.kg-1, i.p.) was shown to markedly and dose-dependently inhibit the decrease of lactate dehydrogenase (LDH) in cerebrum and improve the learning and memory impairment on the step down test. On the four-vessel occlusion model in rats, Hyp(50 and 100 mg.kg-1, i.p.) significantly reduced the decreases of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and LDH activities in the cerebrum. Hyp was also shown to inhibit the increase of nitric oxide (NO) and malondialdehyde (MDA) contents in the cerebrum and promote the recovery of EEG activities. These results suggest that Hyp has protective effect against cerebral ischemia-reperfusion injury via attenuating free radical and NO.

Animals↗

PubMed1998

[Study on mechanical performance of the cerebral aneurysm clip].

Blood vessel tissue mechanical performance and cerebral aneurysm clip mechanical property are investigated. Results show that physical character of cerebral aneurysm clip, such as pressure value, maximum opening width of the blade tip, width, thickness and material is very important for its medical purpose. Surveying instrument is devised successfully.

Biomechanical Phenomena↗

PubMed1998

[In vitro sensitivity of Plasmodium falciparum to chloroquine, piperaquine, pyronaridine and artesunate in Yuxi prefecture of Yunnan province].

AIM: To assess the sensitivity of Plasmodium falciparum to four antimalarials. METHODS: WHO standard in vitro microtest was used. RESULTS: The resistance rates of the malaria parasite to chloroquine, piperaquine pyronaridine and artesunate were 85.7%, 66.7%, 38.1% and 5.0%, respectively. CONCLUSION: Among the antimalarials tested in Yuxi Prefecture, Yunnan Province, high resistance of P. falciparum to chloroquine and piperaquine was found. The sensitivity of P. falciparum in part of the cases to pyronaridine decreased. However, most of the cases were relatively sensitive to artesunate.

Adolescent↗

PubMed1998

[Isolation and identification of triterpenoide compound from Patrinia scabiosaefolia].

In this paper, a triterpenoide was isolated from the roots and rhizomes of Patrinia scabiosaefolia Fish ex Link. Its structure was identified by combination of chemical reactions and spectrum analysis as 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl-hederagenin ester. The compound was found in the Patrinia for the first time.

Chromatography, Thin Layer↗

PubMed1998

[Morphological study on rhizome of Dioscorea gracillima being forgery of Rhizoma Dioscoreae Hypoglaucae].

Rhizome of Dioscorea gracillima is the main forgery of Rhizoma Dioscoreae Hypoglaucae. The paper reports the results of study on chracteristics of its apperance, micriscopical characteristics of cross section and powder, characteristics of inner wall of trachea by scanning electron microscope. Rhizome of Dioscorea gracillima can be distinguished from Rhizoma Dioscoreae Hypoglaucae by above results of study.

Dioscorea↗

PubMed1997

Defective mammopoiesis, but normal hematopoiesis, in mice with a targeted disruption of the prolactin gene.

Prolactin (PRL) has been implicated in numerous physiological and developmental processes. The mouse PRL gene was disrupted by homologous recombination. The mutation caused infertility in female mice, but did not prevent female mice from manifesting spontaneous maternal behaviors. PRL-deficient males were fertile and produced offspring with normal Mendelian gender and genotype ratios when they were mated with heterozygous females. Mammary glands of mutant female mice developed a normal ductal tree, but the ducts failed to develop lobular decorations, which is a characteristic of the normal virgin adult mammary gland. The potential effect of PRL gene disruption on antigen-independent primary hematopoiesis was assessed. The results of this analysis indicated that myelopoiesis and primary lymphopoiesis were unaltered in the mutant mice. Consistent with these observations in PRL mutant mice, PRL failed to correct the bone marrow B cell deficiency of Snell dwarf mice. These results argue that PRL does not play any indispensable role in primary lymphocyte development and homeostasis, or in myeloid differentiation. The PRL-/- mouse model provides a new research tool with which to resolve a variety of questions regarding the involvement of both endocrine and paracrine sources of PRL in reproduction, lactogenesis, tumorigenesis and immunoregulation.

Animals↗

PubMed1997

Up-regulation of cytokine mRNA, adhesion molecule proteins, and MHC class II proteins in salivary glands of TGF-beta1 knockout mice: MHC class II is a factor in the pathogenesis of TGF-beta1 knockout mice.

Mice homozygous for a disrupted TGF-beta1 allele develop multiple lymphoproliferative disorders similar to those seen in the pseudolymphoma of Sjögren's syndrome. At 2 wk of age, these TGF-beta1 mutant mice begin to develop wasting syndrome and die at around 4 to 5 wk of age. We studied salivary glands from symptomatic mutant mice >14 days of age. Reverse transcriptase-PCR analysis showed up-regulation of proinflammatory cytokine genes such as IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, and IFN-gamma in these mutant mice. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1), and MHC class II as well as CD4-positive T lymphocyte infiltration was detected by immunostaining. To elucidate the role of MHC class II, salivary glands from TGF-beta1/MHC class II double knockout mice were used to investigate the expression of adhesion molecules and MHC class II. In spite of the existence of basal intercellular adhesion molecule-1 expression on vessels, there was neither MHC class II expression, enhanced vascular cell adhesion molecule-1 expression, nor lymphocytic infiltration in the salivary glands. These results suggest that MHC class II plays a significant role in the pathogenesis of TGF-beta1 mutant mice. Although the mechanism that initiates multiple inflammatory diseases in these mice remains unclear, the context reported here would provide insight into the immunopathology of Sjögren's syndrome.

Animals↗

PubMed1997

Identification of an insulin-responsive element in the rat insulin-like growth factor-binding protein-3 gene.

The hepatic expression and serum levels of insulin-like growth factor-binding protein-3 (IGFBP-3) are decreased in insulin-dependent and insulin-resistant diabetes. Insulin increases hepatic IGFBP-3 expression by enhancing gene transcription. This report identifies sequences within the IGFBP-3 promoter that are necessary and sufficient for the response to insulin in hepatic nonparenchymal cells. By transient transfection, we mapped the insulin response element to the -1150 to -1124 base pair (bp) region of the rat IGFBP-3 promoter. Three tandem repeats of the -1150 to -1117 bp region conferred insulin responses in a heterologous promoter. Gel shift analyses revealed a 3-fold increase in DNA-protein complex formation with nuclear extracts obtained from insulin-stimulated nonparenchymal cells compared with cells incubated without insulin and revealed 3-4-fold decrease in complex formation with nuclear extracts obtained from the livers of streptozotocin-diabetic rats compared with control rats. Mutational analysis of this 34-bp region showed a core sequence of 10 bp (-1148 to -1139) that is critical for interaction with insulin-induced trans-acting factors. Southwestern blotting revealed a approximately 90-kDa protein that was increased 2-3-fold by the addition of insulin. Thus, we have identified cis-acting DNA sequences that are responsible for regulation of IGFBP-3 transcription by insulin and essential for binding of insulin-responsive nuclear factors.

Animals↗

PubMed1997

Hyperthermia enhances spectrin breakdown in transient focal cerebral ischemia.

Calpain-mediated spectrin degradation is triggered by cerebral ischemia and, when persistent, is thought to signal irreversible neuronal injury. Hyperthermia superimposed upon cerebral ischemia may exacerbate the injury process. In this study, we compared the extent of spectrin degradation in the brains of rats subjected to 1 h of transient proximal middle cerebral artery (MCA) clip-occlusion performed under conditions of cranial normothermia (37 degrees C) or mild cranial hyperthermia (39 degrees C). Immunocytochemical localization of spectrin breakdown products was achieved by the use of a rabbit polyclonal antibody which reacted selectively with calpain-generated fragments of brain spectrin. The perfusion times studied were 1, 4 or 24 h. Following normothermic MCA occlusion, spectrin immunoreactivity was present only occasionally and only in scattered cortical neurons immediately upon reperfusion and 1 h later; all normothermic brains showed space immunoreactivity at 4 h of reperfusion; and no immunoreactivity was detected at 24 h. By contrast, following hyperthermic MCA occlusion, moderate-to-intense immunostaining was present in cortical pyramidal neurons even immediately upon reperfusion and persisted at 1 h of reperfusion. At 4 and 24 h, most brains exhibited dense immunoreactivity associated with morphologically shrunken neurons. Following 24 h survival, semi-thick plastic sections revealed intact neuropil and only selective neuronal necrosis in normothermic rats. By contrast, pan-necrosis was evident 24 h after the hyperthermic ischemic insult. These results indicate that mild cranial hyperthermia superimposed upon transient focal ischemia markedly enhances calpain activation and spectrin degradation; this process appears to be an important mechanism by which hyperthermia exacerbates ischemic injury.

Animals↗

PubMed1997

The inhibitory effect of fluoride on carbachol-induced bovine bronchial contraction.

The effect of sodium fluoride (NaF) on the responsiveness of airway smooth muscle was investigated in bovine bronchial segments. NaF (0.5-10 mM) induced a delayed concentration-dependent active pressure (AP) and reduced the lactate concentration in the solution. Pyruvate (10 mM) increased the NaF-induced contraction. There was a 50 +/- 7% decrease in carbachol (10 microM)-induced AP when bronchi were pretreated with NaF (5 mM) and a 37 +/- 9% decrease when NaF (5 mM) was added during the maintained carbachol-induced contraction. These inhibitory effects were enhanced by KCN and hypoxia. When bronchi were pre-incubated with 10 microM verapamil, a calcium channel inhibitor, the contractile effect of 5 mM NaF was reduced to 8 +/- 3% of the control. PKC activity in bronchial smooth muscle was significantly increased by NaF (5 mM). Staurosporine (30 nM) abolished the contractile effect of NaF. These results suggest that: (1) NaF either contracts or relaxes bronchial smooth muscle depending on the experimental conditions; (2) the relaxing effect is related to the inhibitory action of NaF on glycolysis; (3) the contractile effect of NaF is possibly mediated by modulation of a calcium channel via a PKC-dependent pathway; (4) carbachol-induced contraction is glycolysis pathway dependent in the absence of NaF but switches to oxidative dependent in its presence.

Animals↗

PubMed1997

Different administration schedules of the same dose of 2,5-hexanedione influence the development of neuropathy and the toxicokinetics.

The same total dose (1.2 g/kg/week) of 2,5-hexanedione (2,5-HD) was administered subcutaneously at 100 mg/kg/12 hr, 200 mg/kg/24 hr, and 400 mg/kg/48 hr to three groups of Donryu rats. The peripheral neuropathy induced by 2,5-HD was confirmed by clinical observation every day, and neurophysiological measurements every 4 weeks. During the 15th week of this experiment, 2,5-HD concentrations in plasma 0.5 to 24 hours after injection were determined. It was found that the greater the dose of 2,5-HD per treatment injected, the earlier peripheral neuropathy developed. Toxicokinetic analysis showed that both the values of the area under the plasma concentration versus time curve and the half life of 2,5-HD were increased, but the excretion parameters (Ke) were decreased, in animals treated with 200 mg/kg/24 hr and 400 mg/kg/48 hr 2,5-HD.

Animals↗

PubMed1997

Characterization of mutations in the myotubularin gene in twenty six patients with X-linked myotubular myopathy.

A candidate gene, myotubularin, involved in the pathogenesis of X-linked myotubular myopathy (MTM1) was isolated recently. Mutations originally were identified in 12% of patients examined for 40% of the coding sequence, raising the possibility that additional genes could be responsible for a proportion of X-linked cases. We report here the identification of mutations in 26 of 41 independent male patients with muscle biopsy-proven MTM, by direct genomic sequencing of 92% of the known coding sequence of the myotubularin gene. Eighteen patients had point mutations, including one A/G transition found in four patients which alters a splice acceptor site in exon 12 and leads to a three amino acid insertion. Six patients had small deletions involving <6 bp, while two larger deletions encompassed two or six exons, respectively. No differences were noted among the types of mutations between familial and sporadic cases. However, all of the five patients with a mild phenotype had missense mutations. While 50% of the mutations were found in exons 4 and 12, and three distinct mutations were found in more than one patient, no single mutation accounted for more than 10% of the cases. The low frequency of large deletions and the varied mutations identified suggest that direct mutation screening for molecular diagnosis may require gene sequencing.

Exons↗

PubMed1997

The effect of nitric oxide synthase inhibition on acute platelet accumulation and hemodynamic depression in a rat model of thromboembolic stroke.

The relative importance of hemodynamic factors in the pathogenesis of thrombotic or embolic stroke is unclear. Of particular therapeutic interest are those substances that facilitate vasodilation and the clearance of platelet aggregates in the compromised microvasculature. A likely contributor to these functions is nitric oxide because it is known to inhibit platelet aggregability and promote vascular relaxation. To investigate the involvement of nitric oxide in the hemodynamic changes after experimental ischemia, photochemically induced nonocclusive common carotid artery thrombosis (CCAT) was studied. CCAT is a rat model of unilateral carotid artery stenosis and platelet embolization to the brain. This study characterized the acute hemodynamic consequences of CCAT and the resultant pattern of platelet deposits with and without nitric oxide synthase inhibition by nitro-L-arginine methyl ester (L-NAME). In addition, the subacute local cerebral blood flow changes were studied at 24 hours. Right CCAT was produced in 30 male Wistar rats injected with (111)In-labeled platelets. Between 5 and 15 minutes after thrombosis, rats were treated with either 15 mg/kg of L-NAME (intravenously) or saline vehicle. Hemodynamic changes were studied 30 to 45 minutes after thrombosis using [14C]iodoantipyrine autoradiography. Eight coronal levels were analyzed, and cortical and subcortical regions of interest were defined. Significant increases were observed in total platelets in the ipsilateral hemisphere after L-NAME treatment, and in the distribution of platelets in the anterior frontal and occipital cortices with nitric oxide synthase inhibition, encompassing the anterior and posterior border zone areas of the ipsilateral cortex. Otherwise, foci of labeled platelets were detected throughout the ipsilateral and contralateral hemispheres. Mean local cerebral blood flow images (n = 5) revealed a moderate bilateral global reduction in flow acutely, which normalized in the untreated thrombosed group by 24 hours. In contrast, the L-NAME-treated groups (sham and experimental) had lasting, widespread reductions in flow of approximately 25%. Pairwise comparisons between groups showed that CCAT/L-NAME was significantly different from shams in the corpus callosum and different from L-NAME shams in the internal capsule (P < 0.05) These hemodynamic and platelet accumulation changes may partially account for the aggravation of cognitive and sensorimotor deficits previously reported in this model of thromboembolic stroke.

Animals↗

PubMed1997

Transient middle cerebral artery occlusion by intraluminal suture: I. Three-dimensional autoradiographic image-analysis of local cerebral glucose metabolism-blood flow interrelationships during ischemia and early recirculation.

Using autoradiographic image-averaging strategies, we studied the relationship between local glucose utilization (LCMRglc) and blood flow (LCBF) in a highly reproducible model of transient (2-hour) middle cerebral artery occlusion (MCAO) produced in Sprague-Dawley rats by insertion of an intraluminal suture coated with poly-L-lysine. Neurobehavioral examination at 60 minutes after occlusion substantiated a high-grade deficit in all animals. In two subgroups, LCBF was measured with 14C-iodoantipyrine at either 1.5 hours of MCAO, or at 1 hour of recirculation after suture removal. In two other matched subgroups, LCMRglc was measured with 14C-2-deoxyglucose at 1.5 to 2.25 hours of MCAO, and at 0.75 to 1.5 hours of recirculation after 2 hours of MCAO. Average image data sets were generated for LCBF, LCMRglc, and the LCMRglc/LCBF ratio for each study time. Middle cerebral artery occlusion for 2 hours induced graded LCBF decrements affecting ipsilateral cortical and basal ganglionic regions. After 1 hour of recirculation, LCBF in previously ischemic neocortical regions increased by 40% to 200% above ischemic levels, but remained depressed, on average, at about 40% of control. By contrast, frank hyperemia was noted in the previously ischemic caudoputamen. Mean cortical LCBF values during MCAO correlated highly with their respective LCBF values after 1 hour of recirculation (R = 0.93), suggesting that post-ischemic LCBF recovery is related to the depth of ischemia. Despite focal ischemia, LCMRglc during approximately 2 hours of MCAO was preserved, on average, at near-normal levels; but following approximately 1 h of recirculation, LCMRglc became markedly depressed (on average, 55% of control in previously densely ischemic cortical regions). Regression analysis indicated that this depressed glucose utilization was determined largely by the intensity of antecedent ischemia. By pixel analysis, the ischemic core (defined as LCBF 0% to 20% of control) comprised 33% of the ischemic hemisphere, and the penumbra (LCBF 20% to 40%) accounted for 26%. The penumbra was concentrated at the coronal poles of the ischemic lesion and formed a thin shell around the central ischemic core. During 2 hours of MCAO, the LCMRglc/LCBF ratio within the ischemic penumbra was increased four-fold above normal (average, 179 umol/100 mL). In marked contrast, after approximately 1 h recirculation, this uncoupling had almost completely subsided. The companion study (Zhao et al., 1997) further analyzes these findings in relation to patterns of infarctive histopathology.

Animals↗

PubMed1997

Transient middle cerebral artery occlusion by intraluminal suture: II. Neurological deficits, and pixel-based correlation of histopathology with local blood flow and glucose utilization.

We conducted a pixel-based analysis of the acute hemodynamic and metabolic determinants of infarctive histopathology in a reproducible model of temporary (2-hour) middle cerebral artery occlusion (MCAO) produced in rats by an intraluminal suture. Three-dimensional averaged image data sets of local cerebral blood flow (LCBF) and glucose utilization (LCMRglc) acquired in the companion study (Belayev et al., 1997) either at the end of a 2-hour period of MCAO or after 1 hour of recirculation were comapped (using digitized atlas-templates) with data sets depicting the frequency of histological infarction in a matched animal group (n = 8) in which 2 hours of MCAO was followed by 3-day survival, sequential neuro behavioral examinations, and perfusion-fixation and paraffin-embedding of brains for light-microscopic analysis. All rats developed marked postural-reflex and forelimb-placing deficits at 60 minutes of MCAO, signifying high-grade ischemia. Tactile placing deficits persisted during the 72-hour observation period while visual placing and postural-reflex abnormalities variably improved. Comapping of LCBF and histopathology showed that in those pixels destined to undergo infarction, LCBF measured at 2 hours of MCAO showed a sharp distributional peak centered at 0.14 mL/g/min. In 70% of pixels destined to infarct, LCBF at 2 hours of MCAO was 0.24 mL/g/min or below, and in 89% LCBF was below 0.47 mL/g/min (the upper limits of the ischemic core and penumbra, respectively, as defined in the companion study [Belayev et al., 1997]). Local cerebral glucose utilization measured at approximately 1 hour after 2 hours of MCAO was distributed bimodally in the previously ischemic hemisphere. The major peak, at 22 mumol/100g/min, coincided exactly with the distribution peak of pixels destined to undergo infarction, while in pixels with a zero probability of infarction, LCMRglc was higher by 12 to 13 mumol/100g/min. These results indicate that local blood flow at 2 hours of MCAO is a robust predictor of eventual infarction. Pixels with ischemic-core levels of LCBF (0% to 20% of control) have a 96% probability of infarction, while the fate of the penumbra is more heterogeneous: below LCBF of 0.35 mL/g/min, the probability of infarction is 92%, while approximately 20% pixels in the upper-penumbral LCBF range (30% to 40% of control) escape infarction. Our data strongly support the view that the likelihood of infarction within the ischemic penumbra is highly influenced by very subtle differences in early perfusion.

Animals↗

PubMed1997

Ameliorating effect of erythromycin on bleomycin-induced pulmonary fibrosis: role of alveolar macrophage activation and cytokine release.

The objective of this study was to evaluate the effectiveness of erythromycin (EM) on bleomycin-induced pulmonary fibrosis in rats and its possible mechanisms. Seventy-five rats were divided into three groups. Alveolar macrophages (AM) were harvested through bronchalveolar lavage (BAL) and consecutive changes of tumour necrosis factor-alpha (TNF-alpha) and platelet-derived growth factor (PDGF) in AM supernatant and bronchoalveolar lavage fluid (BALF) were assayed with ELISA and bioassay, respectively. The AM-derived TNF-alpha was elevated on day 3, peaked day 7 and then decreased but remained at higher level until day 28. The AM-derived PDGF was increased on day 3, peaked on day 7 then decreased to non-statistically significant higher level. The TNF-alpha in BALF was increased significantly on day 3 then decreased to normal level; the peak preceded that of AM-derived TNF-alpha. The PDGF in BALF was increased on day 3, peaked on day 7, and then decreased to normal, which exhibited a consecutive change similar to that of AM-derived PDGF. The EM significantly suppressed TNF-alpha and PDGF release by AM, markedly decreased TNF-alpha and PDGF levels in BALF. The EM also lessened the collagen deposition, the lung hydroxyproline comprised 75.44%, 72.72% and 56.24% that of bleomycin-treated group on day 7, 14 and 28, respectively. In conclusion, EM can ameliorate bleomycin-induced pulmonary fibrosis possibly through suppression of TNF-alpha and PDGF as well as the inhibition on accumulation of inflammatory cells in the lung.

Animals↗

PubMed1997

Digital radiology using active matrix readout of amorphous selenium: theoretical analysis of detective quantum efficiency.

A flat-panel x-ray imaging detector using a layer of amorphous selenium (a-Se) for direct conversion of x rays (to charge) and an active matrix for self-scanned readout is being investigated for digital radiology. A theoretical analysis of the spatial frequency dependent detective quantum efficiency (DQE(f)) of the self-scanned a-Se detector is performed based on a model of signal and noise propagation in a cascaded imaging system. Because of the high intrinsic resolution of a-Se and the pixelated active matrix readout method, such detectors are inherently undersampled and aliasing is present. The presampling modulation transfer function (MTF) and aliased noise power spectrum (NPS) of the detector were used in the analysis of DQE(f). It is proven that the aliased NPS for the self-scanned a-Se detectors is white. Since the shape of DQE(f) is determined by the ratio of MTF squared and the NPS, the shape of DQE(f) follows the square of the presampling MTF of the detector as a result of the white NPS. The analysis also shows that DQE(0) is proportional to the pixel fill factor, i.e., the fraction of each pixel area used for image charge collection. The DQE analysis is applied to detector parameters for three x-ray imaging applications: mammography, chest radiography, and fluoroscopy. The effects of pixel fill factor, imaging geometry (i.e., incident angle of x rays), and various sources of electronic noise on the detector DQE(f) are discussed. Strategies for maximizing detector DQE for each x-ray imaging application are proposed.

Models, Theoretical↗

PubMed1997

Digital radiology using active matrix readout of amorphous selenium: construction and evaluation of a prototype real-time detector.

The goal of the present work is to develop a large area, flat-panel solid-state detector for both digital radiography and fluoroscopy. The proposed detector employs a photoconductive layer of amorphous selenium (a-Se) to convert x rays into charge. The charge image formed by the a-Se layer is electronically read out in situ using a two dimensional array of thin film transistors (TFTs), or active matrix. Since the active matrix readout is capable of producing x-ray images in real-time, it can potentially be applied in both radiography and fluoroscopy. In this paper, the imaging performance of this concept is investigated using a prototype x-ray imaging detector. The designs for the active matrix, the peripheral electronic circuits, and the image acquisition system are described. Measurements of x-ray imaging properties of the prototype detector, i.e., x-ray sensitivity, presampling modulation transfer function (MTF), and noise power spectrum (NPS), were performed, and from which the spatial frequency dependent detective quantum efficiency (DQE) of the prototype was derived. The experimental results are in agreement with the results of our theoretical analysis. The factors affecting the imaging performance and methods of improvement in the future are discussed.

Fluoroscopy↗