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Biomedical subjects

W Yao

Publications and source records attributed to W Yao.

At least 37 records · Page 2Linked to original sources

Cancellous bone of aged rats maintains its capacity to respond vigorously to the anabolic effects of prostaglandin E2 by modeling-dependent bone gain.

The present study examined the early effects of prostaglandin (PG)E2 on proximal tibial metaphyses of 20-month-old Wistar male rats. PGE, was given to intact rats for 10 and 30 days at 3mg/kg/day. After multiple in vivo fluorochrome labeling, undecalcified longitudinal sections were subjected to analysis of bone histomorphometry and classification of the contour of the cement line in bone formation units. The latter was used to classify bone formation units into modeling, remodeling and uncertain units. After 10 days of treatment, there was a 2% increase in woven bone formation with the appearance of osteoprogenitor cells and increases in the number of osteoblasts (649%) and osteoid (375%) surfaces. Remodeling and modeling units increased by 56% and 429%. respectively. After 30 days of treatment, there was an increase of 212% of total trabecular bone mass, 60% of which was woven bone. In addition, there were increases in labeling surface (147%), mineral apposition rate (760%), bone formation rates tissue area (BFR/T.Ar, 1920%; BFR/B.Pm, 343%), and bone turnover (BFR/B.Ar, 426%). Osteoblasts and osteoid production at 30 days were 29% and 58% less than at 10 days post-treatment. Modeling and remodeling activity did not differ from that seen at 10 days. In addition, PGE2 treatment tended to stimulate the closing of growth plates and decrease the fatty marrow area. We conclude that the aged skeleton was able to respond vigorously to PGE2 treatment. Massive osteoprogenitors cells, and osteoid and osteoblast formations were observed within 10 days. and dramatic woven and lamellar bone formation was seen at 30 days post-treatment. The anabolic effects were driven mainly by modeling.

Aging↗

Low viscosity Ektacytometry and its validation tested by flow chamber.

The flow chamber was used to observe the orientation and small deformation of red blood cells (RBCs) in a shear flow of low viscosity. With the aid of computer software, the percentage of RBCs oriented to the C=0 orbit (OI)(F) and the degree of deformation (DI)(F) of such RBCs were calculated by processing the photographs. It was found that these parameters were highly correlated, respectively, to the orientation index (OI)(E) and the small deformation index (DI)(E) obtained by our low viscosity Ektacytometry (LVE). Thus, our flow chamber research has provided direct evidence to validate the use of this low viscosity Ektacytometry. Although there are relative merits for the flow chamber method using low viscosity medium, the LVE is more likely to be applied in clinic for its simplicity and convenience.

Animals↗

Bipedal stance exercise enhances antiresorption effects of estrogen and counteracts its inhibitory effect on bone formation in sham and ovariectomized rats.

In this study we employed a raised cage model in combination with estrogen to observe their effects on the proximal tibial metaphysis (PTM) and tibial shaft (TX) in sham-operated or ovariectomized rats. A total of 105 6-month-old female Sprague-Dawley rats were used in the study. Bilateral sham ovariectomy or ovariectomy was performed at day 0 and the rats were housed in normal height or raised cages (RCs) and injected subcutaneously twice per week with 10 microg/kg of 17beta-estradiol (E2) or vehicle for 4 and 8 weeks. Because the time course of bone loss or bone gain distribution was not uniform in the metaphyses of the tibia, we subdivided the PTM into three zones (medial, central, and lateral) to observe the different bone loss or bone gain patterns after ovariectomy and/or raised cages. We found that: (1) E2 alone did not alter bone area or architecture in sham rats, whereas RC alone increased trabecular thickness and area of PTM, but had no effects on TX; (2) Ovx induced most bone loss from the central zone of the PTM and endocortical surface of TX, accompanied by decreased trabecular number and increased bone resorption; (3) E2 alone prevented ovx-induced bone loss by preserving trabecular number and depressing bone resorption; (4) RC alone partially compensated for bone loss following ovx by thickening the surviving trabeculae in lateral and medial zones, and tended to stimulate bone formation and decrease bone resorption; and (5) RC plus E2 increased trabecular bone area by having an additive effect on bone resorption and bone turnover. RCs helped to prevent the depressive effect of estrogen on periosteal bone formation. In conclusion, early and rapid bone loss occurred in the central zone of the metaphysis and endocortical surface after ovx. Estrogen replacement therapy prevented this loss. Raised cages partially compensated for bone loss following ovx by thickening the trabeculae in the lateral area of the metaphysis and decreased endocortical erosion. Combination treatment added bone to the PTM and prevented the decrease of periosteal bone formation after estrogen administration.

Animals↗

Ultrasonographic texture analysis of parenchymatous organs by the four-neighborhood-pixels algorithm: clinical experiment.

OBJECTIVE: The parenchyma of organs such as liver, thyroid, and mammary gland during climacterium have common ultrasonographic textural features, which together form what we call small-dot-structure texture. To study this texture we designed the 4-neighborhood-pixels algorithm, an ultrasonographic texture analysis algorithm. The objective of this study was to confirm whether the 4-neighborhood-pixels algorithm can reflect the features of small-dot-structure texture. METHODS: A changed small-dot-structure texture and 3 other textures were compared with the normal small-dot-structure texture in 4 groups, and a histogram algorithm was used for contrast with the 4-neighborhood-pixels algorithm. RESULTS: The 4-neighborhood-pixels algorithm could reflect all the textural differences, but the histogram algorithm could reflect only some of them. CONCLUSIONS: The 4-neighborhood-pixels algorithm is a good algorithm for analyzing ultrasonographic small-dot-structure texture. Not only can it reflect changes in the small-dot-structure texture, but it can also differentiate between small-dot-structure and non-small-dot-structure textures.

Adipose Tissue↗

[Effect of radiation with 60Co on RBC membrane elastic shear modulus and membrane viscosity].

RBC membrane shear elastic modulus and membrane viscosity are two important indexes reflecting RBC membrane viscoelasticity. Their variation was investigated in this study after rabbits were radiated with 60Co. With a new ektacytometer, we measured the small deformation index (DId) and the half-time of deformation relaxation (t0.5) of RBC in flow field then we calculated RBC membrane shear elastic modulus and membrane viscosity. We found that the value of RBC membrane shear elastic modulus and membrane viscosity continuously increased from 0 to 16th day then continuously decreased and tended to be stable on 60th day or so. The reason may lie in the variation of proportion of new and old RBC in blood and variation of microconformation of RBC membrane after rabbits were radiated with 60Co.

Animals↗

[Effects of the alterations of membrane shear elastic modulus and viscosity on the deformation and orientation of RBCs].

Neuraminidase can partly remove the surface charge of RBCs through a biochemical interaction; thus it can give rise to alterations in the microstructure of membrane, the shear elastic modulus (E) and the viscosity(micron) of membrane. Changing the time of treatment and the dose of neuraminidase and using a new ektacytometry that can separate deformation index DI into orientation index (DI)or and small deformation index (DI)d for RBCs in shear flow field of low viscosity, we measured (DI)d and the half time t0.5 when the DI recovered to half of the maximum in the process of relaxation for every treated sample. (DI)d and t0.5 were put respectively into the RBC membrane shear elastic modulus formula and the membrane viscosity formula which were put forward by Wen Zong-yao and Yan Zong-yi et al[1]. The rules of the alterations of E and micron were obtained. We also measured DI and (DI)or. It was found that E and micron increased greatly but DI and (DI)or decreased when the dose of neuraminidase and the time of treatment were increased. There was a contrary correlation between them. These data demonstrated that the increase of E and micron weakened the deformability and the ability of orientation of RBCs.

Animals↗

Effect of Cr(VI) exposure on sperm quality: human and animal studies.

The semen status of male workers occupationally exposed to hexavalent chromium(VI) was investigated. Sperm counts from exposed workers were 47.05+/-2.13 x 10(6)/ml and those from control group 88.96+/-3.40 x 10(6)/ml. Sperm motility decreased from 81.92+/-0.41% for the control group to 69.71+/-0.93% for the exposed workers. The levels of zinc, lactate dehydrogenase (LDH), and lactate dehydrogenase C4 isoenzyme (LDH-x) in seminal plasma for the exposed workers were 1.48+/-0.07 micromol/ml, 1.05+/-0.02 x 10(3) U, and 0.47+/-0.01 x 10(3) U, respectively, which were significantly lower than those of 5.72+/-0.15 micromol/ml, 1.49+/-0.02 x 10(3) U, and 0.78+/-0.15 x 10(3) U for the control group, respectively. Follicle stimulating hormone (FSH) (7.34+/-0.34 x 10(-3) IU/ml) in serum from the exposed workers was significantly higher than that (2.41+/-0.08 x 10(-3) IU/ml) from the control group. On the other hand, there were no significant differences in semen volume, semen liquefaction time, luteinizing hormone (LH) level in serum, and Cr concentration in both serum and seminal plasma between the exposed workers and the control group. Feeding Cr(VI) to rats significantly reduced the epididymal sperm counts from 87.40+/-3.85 x 10(6)/g epididymis in control group to 21.40+/-1.20 x 10(6)/g epididymis at a CrO(3) dose of 10 mg/kg body weight and to 17.48+/-1.04 x 10(6)/g epididymis at a CrO(3) dose of 20 mg/kg body weight. Exposure of rats to Cr(VI) also significantly increased the sperm abnormality from 2.75+/-0.06% in the control group to 6.68+/-0.32% in the exposed group at a CrO(3) dose of 10 mg/kg body and to 7.6+/-0.15% at a CrO(3) dose of 20 mg/kg body weight. In exposed rats, there was visible disruption in germ cell arrangement near the walls of the seminiferous tubules. The diameters of seminiferous tubules in exposed rats were smaller. These results suggest that occupational exposure to chromium(VI) leads to alteration of semen status and may affect the reproductive success of exposed workers.

Animals↗

Effect of ipratropium bromide on airway and pulmonary muscarinic receptors in a rat model of chronic obstructive pulmonary disease.

OBJECTIVE: To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). METHODS: This model was developed by exposure of rats to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. RESULTS: Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038 +/- 0.011, pmol/mg protein) and affinity (Kd, 23 +/- 11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030 +/- 0.008 and 29 +/- 19, respectively, P > 0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). CONCLUSION: A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide.

Animals↗

Effect of 60Co irradiation on characteristics of hemorheology in rabbits.

A high-dose (7 Gy) whole-body 60Co irradiation for a short period caused disturbances of hematopoietic function. A decrease in the hematocrit of the circulating blood lasted for about 15 days, thus forming an anemic animal model. We studied the influence of high-dose 60Co irradiation on hemorheologic parameters: percentage of reticulocytes, RBC deformability, sedimentation rate and plasma fibrinogen concentration in the rabbit. It was found that the plasma fibrinogen concentration increased to twice more than control level and that percentage of reticulocytes in circulation disappeared immediately after irradiation. The deformation index of RBCs in shear flow decreased from a value of 58% down to a value of 42% in the first two weeks and gradually returned to control levels about 40 days after 60Co irradiation. Our results showed that a short period of high-dose 60Co irradiation caused severe and relatively long-lasting damage of hematopoietic system in animals' body.

Animals↗

[Image analysis of airway remodeling and responsiveness in asthmatic guinea pig].

OBJECTIVE: To observe the mechanism of airway remodeling and changes of airway responsiveness in guinea pig model of asthma. METHODS: 40 guinea pigs were randomly divided into two groups: control (20) and asthmatic group (20). After incubating with different stimulus, bilateral lung tissue section were stained with HE. Using image analysis system to measure the airway internal perimeter, wall area, external perimeter, etc. and calculate percentage of muscle shortening (PMS) according to formula. RESULTS: (1) The airway wall thickness (WA/Pi) in asthmatic group and control group were (10.0 +/- 2.0) and (7.9 +/- 2.1) micrometer(2)/micrometer, respectively. The bronchial smooth muscle thickness in asthmatic group and control group were (4.8 +/- 1.5) and (3.1 +/- 2.0) micrometer(2)/micrometer, respectively. Both were statistically significant (P < 0.01). The number of bronchial smooth muscle nucleus in asthmatic group (0.012 3 +/- 0.002 7/micrometer) was higher compared with control (0.010 +/- 0.003/micrometer) (P < 0.05). (2) Responsiveness of airway smooth muscle to adenosine (represented by PMS) in asthmatic group and control were 0.34 +/- 0.07 and 0.29 +/- 0.08, respectively (P < 0.05). When combined with aminophyline, PMS in asthmatic group was 0.26 +/- 0.07. There was statistically significant difference when compared with adenosine alone (0.34 +/- 0.07) (P < 0.01). (3) PMS to acetylcholine in asthmatic group and control were 0.24 +/- 0.04 and 0.19 +/- 0.06, respectively (P < 0.05). When combined with heparin, PMS in asthmatic group was 0.20 +/- 0.04. There was statistically significant difference when compared with acetylcholine alone (0.24 +/- 0.04) (P < 0.05). CONCLUSIONS: The main reason of airway remodeling in asthma is due to bronchial smooth muscle hyperplasia. Aminophylline and heparin may inhibit the responsiveness of airway to adenosine and acetylcholine respectively.

Acetylcholine↗

[Study on the muscarinic receptor and its subtypes in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the M receptor and its subtypes in the lung tissue of patients with chronic obstructive pulmonary disease (COPD). METHODS: Muscarinic cholinergic receptors have been identified and characterized by radioligand binding assay in the lung tissue specimens of patients with COPD. Competitive binding experiments with pirenzepine and methoctramine were used to characterize muscarinic subtypes. RESULTS: The contents of M-receptor were (64 +/- 10), (42 +/- 18) fmol/mg. protein in normal group and COPD patients respectively. No significant difference was observed in antagonist affinity (K(D)) among normal group and COPD patients. The ratio of subtype M(1) was higher in COPD patients (67.2 +/- 2.7)% than in normal group (74.2 +/- 4.8)%, M(2) was lower [(29.3 +/- 1.7)% vs (16.8 +/- 4.4)%] and M(3) was higher [(3.6 +/- 2.9) % vs (9.3 +/- 4.1)%] respectively. CONCLUSION: The number of muscarinic cholinergic receptors is decreased in COPD patients, but the ratios of subtype M(1) and M(3) are increased and the subtype M(2) is decreased. The changes of the distribution of the subtypes of M-receptors is an important pathophysiologic change of COPD.

Female↗

[The development of cerebral circulation analyzer].

In this paper a new cerebral circulation analyzer is introduced, inducing the main structure, the operating principle, the software program and its clinical applications. We can get the cerebrovascular hemodynamics indexes such as resistance, compensatorg blood flow etc., from the blood velocity, pressure waveform, and arterial diameter detected in carotid and vertebral arteries.

Algorithms↗

[Development and clinical application of the full automatic animal rearing cabin of low oxygen and high carbon dioxide].

This paper introduces a kind of automatic animal rearing cabin of low oxygen and high carbon dioxide. It can mimic the environment of low oxygen and high carbon dioxide at atmospheric pressure and automatically measure and control the concentrations of oxygen and carbon dioxide as well as temperature and humidity in the cabin. The system may provide the equipment support for clinical COPD study. The clinical applications show that the cabin with accurate measurement and control is practical and reliable.

Air Conditioning↗

Urotensin II receptor in the rat airway smooth muscle and its effect on the rat airway smooth muscle cells proliferation.

OBJECTIVE: To investigate the characteristics of urotensin II (U-II) receptor in the rat airway smooth muscle and the effect and signal transduction pathway of U-II on the proliferation of airway smooth muscle cells. METHODS: Using 125I-UII binding assay to measure the Bmax and Kd of U-II receptor. Using the 3H-TdR incorporation to determine the effect of U-II on the proliferation of airway smooth muscle cells and its signal transduction pathway. Using Fura-2/AM to measure the effect of U-1I on the cytosolic free calcium concentration. RESULTS: 1. 125I-UII binding increased with the time and reached saturation at 45 min. The B(max0 was (11.36 +/- 0.37)fmol/mg pr and Kd was (4.46 +/- 0.61) nmol/L. 2. U-II increased 3H-TdR incorporation of the airway smooth muscle cells in a dose-dependent manner. 3. H7, PD98059 and nicardipine, inhibitors of PKC, MAPK, calcium channel, respectively, significantly inhibited U-II-stimulated 3H-TdR incorporation of airway smooth muscle cells. W7, inhibitor of CaM-PK, had no effect. 4. Cyclosporin A, inhibitor of CaN, inhibited 3H-TdR incorporation of the airway smooth muscle cells induced by U-II in a dose-dependent manner. 5. U-II promoted cytosolic free calcium concentration increase by 18%. CONCLUSIONS: 1. There was U-II receptor in the rat airway smooth muscle. 2. The effect of U-II-stimulated 3H-TdR incorporation of airway smooth muscle cells was mediated by such signal transduction pathway as Ca2+, PKC, MAPK and CaN, etc.

Animals↗

Overview: animal models of osteopenia and osteoporosis.

Prior to initiating a clinical trial in a post-menopausal osteoporosis study, it is reasonable to recommence the evaluation of treatment in the 9-month-old ovariectomized female rat. A female rat of this age has reached peak bone mass and can be manipulated to simulate clinical findings of post-menopausal osteoporosis. Ample time exists for experimental protocols that either prevent estrogen depletion osteopenia or restore bone loss after estrogen depletion. More time can be saved by acceleration of the development of the osteopenia by combining ovariectomized (OVX) plus immobilization (IM) models. Methods like serum biochemistry, histomorphometry and densitometry used in humans are applicable in rats. Like most animal models of osteopenia, the rat develops no fragility fractures, but mechanical testing of rat bones substitutes as a predictor of bone fragility. Recent studies have shown that the prevailing activity in cancellous and cortical bone of the sampling sites in rats is remodeling. The problems of dealing with a growing skeleton, the site specificity of the OVX and IM models, the lack of trabecular and Haversian remodeling and the slow developing cortical bone loss have been and can be overcome by adding beginning and pre-treatment controls and muscle mass measurements in all experimental designs, selecting cancellous bone sampling sites that are remodeling, concentrating the analysis of cortical bone loss to the peri-medullary bone and combining OVX and IM in a model to accelerate the development of both cancellous and cortical bone osteopenia. Not to be forgotten is the distal tibia site, an adult bone site with growth plate closure at 3 months and low trabecular bone turnover and architecture similar to human spongiosa. This site would be most challenging to the action of bone anabolic agents. Data about estrogen-deplete mice are encouraging, but the ovariectomized rat model suggests that developing an ovariectomized mouse model as an alternative is not urgent. Nevertheless, the mouse model has a place in drug development and skeletal research. In dealing with drug development, it could be a useful model because it is a much smaller animal requiring fewer drugs for screening. In skeletal research mice are useful in revealing genetic markers for peak bone mass and gene manipulations that affect bone mass, structure and strength. When the exciting mouse glucocorticoid-induced bone loss model of Weinstein and Manolagas is confirmed by others, it could be a significant breakthrough for that area of research. Lastly, we find that the information generated from skeletal studies of nonhuman primates has been most disappointing and recommend that these expensive skeletal studies be curtailed unless it is required by a regulatory agency for safety studies.

Journal Article↗

A novel method to 'exercise' rats: making rats rise to erect bipedal stance for feeding - raised cage model.

We employed a novel method to exercise rats: making them rise to bipedal stance for feeding using raised cages. We studied its effects on the skeletons of 6 and 10-month-old intact or orchidectomized (ORX) rats. Body and hindlimb muscle weights, tibial BMC and periosteal cortical bone formation increased after housing in raised cages, but more so in 6-month-old animals than in 10-month-old ones. In 6-month-old orchidectomized rats, raised cages partially prevented ORX-induced bone loss by stimulating periosteal cortical bone (TX) formation and decreased bone resorption next to marrow. In 10-month-old male orchidectomized rats, raised cages also decreased the endosteal and trabecular bone resorption, but not enough to prevent completely ORX-induced net bone losses. Because the osteogenic effects of raised cages alone were only partial, we also studied the interaction between raised cage and prostaglandin E(2) (PGE(2)) in 10-month-old retired female breeders. When treated with combined raised cage and PGE(2), both cortical (TX) and trabecular bone mass of the proximal tibial metaphysis and lumbar vertebral body increased over either raised cages or PGE(2) treatment alone, that was accompanied by dramatic increased bone formation at periosteal and endosteal surfaces. Thus making rats rise to erect bipedal stance for feeding helps to prevent bone loss after orchidectomy; it amplifies the anabolic effects of PGE(2), and it provides an inexpensive, non-invasive and reliable way to increase mechanical loading of certain bones of the rat skeleton.

Journal Article↗

Inactivation of germline mutant APC alleles by attenuated somatic mutations: a molecular genetic mechanism for attenuated familial adenomatous polyposis.

Germline mutations of the adenomatous polyposis coli (APC) tumor-suppressor gene result in familial adenomatous polyposis (FAP). Patients with FAP typically develop hundreds to thousands of benign colorectal tumors and early-onset colorectal cancer. A subset of germline APC mutations results in an attenuated FAP (AFAP) phenotype, in which patients develop fewer tumors and develop them at an older age. Although a genotype-phenotype correlation between the locations of APC germline mutations and the development of AFAP has been well documented, the mechanism for AFAP has not been well defined. We investigated the mechanism for AFAP in patients carrying a mutant APC allele (APC(AS9)) that has a mutation in the alternatively spliced region of exon 9. APC(AS9) was found to down-regulate beta-catenin-regulated transcription, the major tumor-suppressor function of APC, as did the wild-type APC. Mutation analysis showed that both APC(AS9) and the wild-type APC alleles were somatically mutated in most colorectal tumors from these patients. Functional analysis showed that 4666insA, a common somatic mutation in APC(AS9) in these tumors, did not inactivate the wild-type APC. Our results indicate that carriers of APC(AS9) develop fewer colorectal tumors than do typical patients with FAP because somatic inactivation of both APC alleles is necessary for colorectal tumorigenesis. However, these patients develop colorectal tumors more frequently than does the general population because APC(AS9) is inactivated by mutations that do not inactivate the wild-type APC.

Adenomatous Polyposis Coli↗