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Biomedical subjects

X Wang

Publications and source records attributed to X Wang.

At least 235 records · Page 13Linked to original sources

Mechanism-based quantitative structure-phytotoxicity relationships comparative inhibition of substituted phenols on root elongation of Cucumis sativus.

Phytotoxicity of selected substituted phenols to Cucumis sativus (log1/RC50, root elongation half inhibition concentration [mol/L] in logarithmic form) was determined by using a root elongation inhibition method and quantitative structure-activity relationships (QSARs) were developed. Hydrophobicity, described by 1-octanol/water partition coefficient in logarithmic form (log Kow) and electronic effect (characterized by the energy of the lowest unoccupied orbital, Elumo) proved to contribute mainly to the phytotoxicity of phenols in this study. Log Kow was used as a probe to classify the tested chemicals into subsets according to the modes of toxic action. The result indicated that the substituted phenols fell into two classes in general: narcotic phenols and bioreactive phenols. Most phenols elicited their toxic response via a polar narcosis mechanism and an excellent log Kow-dependent QSAR was developed (log1/RC50 = 0.94 log Kow + 2.04, n = 22, r2adj = 0.89). Selected phenols with bioreactive substructures exhibited elevated bioreactive toxicity and a strong Elumo-dependent correlation was achieved (log1/RC50 = -0.91 Elumo + 2.73, n = 6, r2adj = 0.81). This implied that their reactive toxicity involved mainly their in vivo electrophilic reactions. In an effort to model all chemicals without regard to their mechanisms, a highly predictive response-surface was developed with the phytotoxicity, hydrophobicity, and electrophilic reactivity (log1/RC50 = 0.66 log Kow - 0.57 Elumo + 2.31, n = 28, r2adj = 0.88).

Biological Availability↗

Shear stress induces caveolin-1 translocation in cultured endothelial cells.

Considering that vascular endothelial caveolae could be flow sensors converting mechanical stimuli into chemical signals transmitted into the cell, this work studied, in vitro, the change of caveolin-1 expression and distribution of cultured endothelial cells exposed to laminar flows. Experimental results showed that, in control cells, caveolin-1 were primarily localized on the cell surface, and presented some local concentrations. In cells exposed to laminar flows, caveolin-1 distribution showed a time-dependent variation. After 24 h of shear (1.0 Pa), the expression of caveolin-1 increased and a local caveolin-1 concentration was found, in most cells, at the upstream side of the cell body where the hydrostatic pressure and the spatial gradient of shear stress were at a maximum. As a comparison, tumor necrosis factor-a induced a decrease of caveolin-1 in the cells.

Caveolin 1↗

Dauer juvenile longevity and stress tolerance in natural populations of entomopathogenic nematodes: is there a relationship?

Qualitative and quantitative genetic analysis of life span in experimental adult animals predicts that resistance to stress and longevity are positively correlated, but such studies on field populations of animals are rare. We tested this hypothesis using dauer juveniles of 15 natural populations of the entomopathogenic nematode, Heterorhabditis bacteriophora, collected from diverse localities. Dauer juvenile longevity at 25 degrees C in autoclaved tap water and tolerance to major environmental stresses including heat (survival at 40 degrees C for 2 h), ultraviolet (UV) radiation (original virulence remaining after exposure to 302 nm UV for 5 min), hypoxia (survival at approximately 0% dissolved O2 at 25 degrees C for 96 h), and desiccation (survival in 25% glycerol at 25 degrees C for 72 h) differed significantly among populations. Intrinsic dauer juvenile longevity, defined as the number of weeks to 90% mortality (LT90) estimated using probit analysis of nematode survival data at 25 degrees C varied between 6 and 16 weeks among populations. Longevity was most strongly correlated with heat followed by UV and hypoxia tolerance, respectively, but showed no correlation with desiccation tolerance. The strong positive correlation of longevity with heat tolerance was further confirmed through principal components analysis which showed almost identical variance for heat and longevity. Among the stress factors, only UV tolerance was positively correlated with heat and hypoxia tolerance. Differences in longevity and stress tolerance in nematode populations isolated from a single 200 m2 grassland locality further support another hypothesis that population structure of heterorhabditid nematodes is highly fragmented, thus suggesting the existence of metapopulation dynamics.

Animals↗

Ca(2+) removal mechanisms in freshly isolated rabbit aortic endothelial cells.

Calcium removal from the cytoplasm was investigated in freshly isolated aortic endothelial cells by monitoring changes in intracellular calcium ([Ca(2+)](i)) using ratiometric fura-2 fluorimetry. Blockade of the Na(+)/Ca(2+) exchanger (NCX) by replacement of external sodium with equi-molar N-methyl-D-glutamine (0Na PSS) decreased the removal rate by 52%. Blockade of the sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) by cyclopiazonic acid (CPA) decreased the removal rate by 50%. Simultaneous application of CPA and 0Na PSS did not reduce the removal rate any further (53%). The lack of additivity of these two procedures, suggests that SERCA and the NCX function in series to lower [Ca(2+)](i). In addition, in the absence of extracellular Ca(2+), removal of external Na(+) markedly reduced the rate of loss of Ca(2+) from the ER further supporting the hypothesis that NCX is functionally linked to ER calcium release channels, and thus, plays an important role in ER calcium unloading. To investigate the mechanism for the coupling of NCX and SERCA, the same protocols as described above were repeated after treating the cells with cytochalasin D, which disrupts the cytoskeleton. This treatment uncoupled the NCX from SERCA, as evidenced by the resulting additive inhibitory effects of application of CPA and removal of extracellular Na(+) on the rate of Ca(2+) removal from the cytoplasm. These data suggest that in endothelial cells NCX and SERCA function in series to remove about half of the free Ca(2+) from the cytosol, while PMCA contributes to the other half of the Ca(2+) removal process.

Acetylcholine↗

Human brain plasticity: an emerging view of the multiple substrates and mechanisms that cause cortical changes and related sensory dysfunctions after injuries of sensory inputs from the body.

Injuries of peripheral inputs from the body cause sensory dysfunctions that are thought to be attributable to functional changes in cerebral cortical maps of the body. Prevalent theories propose that these cortical changes are explained by mechanisms that preeminently operate within cortex. This paper reviews findings from humans and other primates that point to a very different explanation, i.e. that injury triggers an immediately initiated, and subsequently continuing, progression of mechanisms that alter substrates at multiple subcortical as well as cortical locations. As part of this progression, peripheral injuries cause surprisingly rapid neurochemical/molecular, functional, and structural changes in peripheral, spinal, and brainstem substrates. Moreover, recent comparisons of extents of subcortical and cortical map changes indicate that initial subcortical changes can be more extensive than cortical changes, and that over time cortical and subcortical extents of change reach new balances. Mechanisms for these changes are ubiquitous in subcortical and cortical substrates and include neurochemical/molecular changes that cause functional alterations of normal excitation and inhibition, atrophy and degeneration of normal substrates, and sprouting of new connections. The result is that injuries that begin in the body become rapidly further embodied in reorganizational make-overs of the entire core of the somatosensory brain, from peripheral sensory neurons to cortex. We suggest that sensory dysfunctions after nerve, root, dorsal column (spinal), and amputation injuries can be viewed as diseases of reorganization in this core.

Acute Disease↗

Early treatment with lexipafant, a platelet-activating factor-receptor antagonist, is not sufficient to prevent pulmonary endothelial damage after intestinal ischaemia and reperfusion in rats.

BACKGROUND: Intestinal ischaemia-reperfusion can lead to pulmonary injury characterised by increased macromolecular leakage and leukocyte sequestration. Important mediators of ischaemia-reperfusion-associated injury include polymorphonuclear granulocytes and platelet-activating factor. AIM: To investigate the potential therapeutic inhibition of platelet-activating factor in intestinal ischaemia-reperfusion associated pulmonary injury, by use of a potent platelet-activating factor-receptor antagonist, lexipafant. METHODS: Rats were subjected to 30 minutes of intestinal ischaemia followed by 3 or 12 hours reperfusion. Lexipafant or saline was given intraperitoneally after 30 minutes reperfusion. RESULTS: Increased leakage of radiolabelled human serum albumin was found in the lungs after intestinal ischaemia followed by 3 or 12 hours reperfusion. Administration of lexipafant did not significantly prevent the increased leakage. Pulmonary myeloperoxidase content increased after intestinal ischaemia-reperfusion, indicating polymorphonuclear granulocyte sequestration through the pulmonary endothelium. The increase in interleukin-1beta seen after 3 hours reperfusion was partly reversed by lexipafant. CONCLUSIONS: Pulmonary injury occurred following intestinal ischaemia-reperfusion, characterised by increased leakage of radiolabelled albumin over the endothelial barrier; correlating with increased pulmonary myeloperoxidase-content, implying involvement of polymorphonuclear granulocytes in the pathogenesis of remote organ injury after intestinal ischaemia-reperfusion. Lexipafant did not significantly decrease severity of pulmonary damage.

Animals↗

Age- and gender-related differences in bone mineral status and biochemical markers of bone metabolism in Northern Chinese men and women.

The aim of this study was to provide insight into the bone mineral status and biochemical markers of bone metabolism in a Chinese population from Shenyang, in the north of China, where hip fracture incidence is low. A total of 194 healthy men and women, aged 25-35 years and 65-75 years, were studied. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) was measured using dual-energy X-ray absorptiometry. Fasting blood and 24 h urine samples were collected for bone alkaline phosphatase (bAP), osteocalcin, calcium, phosphate, and free deoxypyridinoline (Dpd). Both older women and men had lower BMD compared with younger women and men by 27.2 +/- 3.0% (mean +/- SE) and 9.8 +/- 3.0% at the LS and 22.0 +/- 3.4% and 12.8 +/- 3.4% at the FN, respectively, after adjusting for bone and body size (p < 0.01). BMD at the two sites was lower in older women than in older men by 10.7 +/- 4.1% and 10.2 +/- 4.2%, respectively, after size correction (p < 0.05). Plasma bAP, osteocalcin, calcium, and phosphate concentrations were higher in older women than younger women by 69.3 +/- 9.7%, 77.2 +/- 11.1%, 7.5 +/- 2.3%, and 8.0 +/- 3.8%, respectively, and older men by 67.6 +/- 11.1%, 72.1 +/- 11.0%, 7.7 +/- 2.3%, and 23.8 +/- 3.8%, respectively (p < 0.01). However, plasma osteocalcin, calcium, and phosphate concentrations were lower in older men compared with their younger counterparts by 35.6 +/- 11.0%, 8.7 +/- 2.3%, and 14.1 +/- 3.8%, respectively (p < 0.05). Urinary calcium and phosphate output were lower in older men compared with younger men by 48.0 plus minus 10.3% and 27.6 +/- 6.9%, respectively (p < 0.01), whereas there were no differences between older and younger women. No differences in Dpd between older and younger groups were found. This study demonstrates that bone mineral status is lower in older people in Shenyang, as has been shown in populations elsewhere. The pronounced low bone mineral status in older women may be associated with increased bone turnover, which was not observed in older men.

Adult↗

Age-related changes in the collagen network and toughness of bone.

The hypothesis of this study is that the mechanical integrity of the collagen network in bone deteriorates with age, and such adverse changes correlate with the decreased toughness of aged bone. To test the hypothesis, 30 human cadaveric femurs from donors ranging from 19 to 89 years of age were tested to determine the age-related changes in the mechanical properties of demineralized bone and fresh bone samples. Along with bone porosity, bone density, and weight fractions of the mineral and organic phases, collagen denaturation and concentrations of collagen cross-links (HP, hydroxylysylpyridinoline; LP, lysylpyridinoline; PE, pentosidine) were determined for these bone specimens as a function age. Analysis of variance (ANOVA) showed that age-dependent changes were reflected in the decreased strength, work to fracture, and fracture toughness of bone; in the decreased strength, elastic modulus, and work to fracture of the collagen network; as well as in the increased concentration of pentosidine (a marker of nonenzymatic glycation) and increased bone porosity. Regression analyses of the measured parameters showed that the age-related decrease in work to fracture of bone (especially its postyield portion) correlated significantly with deterioration in the mechanical integrity of the collagen network. The results of this study indicate that the adverse changes in the collagen network occur as people age and such changes may lead to the decreased toughness of bone. Also, the results suggest that nonenzymatic glycation may be an important contributing factor causing changes in collagen and, consequently, leading to the age-related deterioration of bone quality.

Adult↗

Genistein, a soybean isoflavone, affects bone marrow lymphopoiesis and prevents bone loss in castrated male mice.

Soybean isoflavones exhibit selective effects on bone metabolism in postmenopausal women as well as in ovariectomized animals. Recently, the role of estrogen in bone metabolism in men has also received attention, because a man with a mutated estrogen receptor-alpha (ER(alpha)) gene will exhibit osteoporotic phenotypes. To examine the possible role of genistein, a soybean isoflavone, in bone marrow hemopoiesis and bone metabolism in men, male mice were orchidectomized (orx) and treated with genistein (0.4-0.8 mg/day) or 17beta-estradiol (E(2); 0.03 microg/day) subcutaneously for 3 weeks. In orx mice, seminal vesicle weight decreased markedly, and it was not affected by the administration of genistein or E(2). The number of bone marrow cells was markedly increased after orx, and the majority was B-220 weakly positive pre-B cells. Increased B-lymphopoiesis was restored completely by E(2) or genistein administration. In orx mice, bone mineral density of the femur decreased markedly, and this bone loss was prevented to a significant extent by treatment with genistein as well as E(2). Histomorphometry showed that the trabecular bone volume in the femoral distal metaphysis decreased markedly after orx, and genistein and E(2) prevented this bone loss. These results suggest that soybean isoflavones prevent bone loss due to androgen deficiency in males.

Animals↗

Molecular analysis of multiple cytochrome P450 genes from the malaria vector, Anopheles gambiae.

Cytochrome P450s are a superfamily of haemoproteins, important in the metabolism of endogenous compounds and xenobiotics. As a first step to elucidating the role of this family in insecticide resistance in the malaria mosquito, Anopheles gambiae, we have cloned and mapped multiple P450 genes. Sixteen cDNAs encoding full-length P450s were cloned and physically mapped to the mosquito's polytene chromosomes. Fourteen of these encode putative CYP6 proteins and two encode P450s belonging to the CYP9 class. Eighteen new A. gambiae Cyp4 P450 genes were identified using degenerate PCR primers, cDNAs were detected for ten and in situ locations for thirteen members of this gene family.

Amino Acid Sequence↗

Manipulation of colonic bacteria and volatile fatty acid production by dietary high amylose maize (amylomaize) starch granules.

AIMS: To study the effects of amylomaize starch and modified (carboxymethylated and acetylated) amylomaize starches on the composition of colonic bacteria and the production of volatile fatty acids, in mice. METHODS AND RESULTS: Balb/c mice were fed with experimental diets containing various amount of amylomaize and modified amylomaize starches. Colonic bacterial populations and short-chain fatty acids were monitored. Results showed that the increases in indigenous bifidobacteria were detected in mice fed all starches tested; however, the highest numbers were observed in the group fed with 40% unmodified amylomaize starch. The starch type influenced the populations of indigenous Lactobacillus, Bacteroides and coliforms. High Lactobacillus numbers were achieved in the colon of mice fed with high concentration of amylomaize starch. Acetylated amylomaize starch significantly reduced the population of coliforms. In addition, orally dosed amylomaize utilizing bifidobacteria reached their highest levels when fed together with amylomaize or carboxymethylated amylomaize starch and in both cases butyrate levels were markedly increased. CONCLUSIONS: These results indicate that different amylomaize starches could generate desirable variation in gut microflora and that particular starches may be used to selectively modify gut function. SIGNIFICANCE AND IMPACT OF STUDY: Amylomaize starch appeared to enhance the desirable composition of colonic bacteria in mice, and suggested it possessed the potential prebiotic properties. Therefore, resistant starch and its chemical derivatives may exert beneficial impacts to the human colon.

Amylose↗

A 20% dose reduction of the original CISCA/VB regimen allows better tolerance and similar survival rate in disseminated testicular non-seminomatous germ-cell tumors: final results of a phase III randomized trial.

BACKGROUND: This prospective randomized clinical trial was designed to compare the efficacy of a low-dose regimen of cisplatin, doxorubicin and cyclophosphamide alternated with vinblastine and bleomycin (CISCA/VB) with the original CISCA/VB regimen in patients with disseminated nonseminomatous germ-cell tumors (NSGCT) and a predicted favorable outcome. PATIENTS AND METHODS: One hundred and twenty-five patients with disseminated NSGCT and a predicted favorable outcome according to the M.D. Anderson Cancer Center classification [testicular primary and human chorionic gonadotropin (hCG) serum level <50000 mIU/ml] were randomized to receive the original CISCA/VB regimen (100% dose) or a low-dose CISCA/VB regimen (80% dose). RESULTS: Among the 124 eligible patients, there was no significant difference in the number of patients in the two treatment arms who achieved a complete response to therapy: 53 of 65 patients (82%) on the original CISCA/VB regimen and 53 of 59 patients (90%) on the low-dose CISCA/VB regimen (P = 0.29). Overall, the original CISCA/VB regimen resulted in a significantly higher relative dose intensity (P <0.0001). After a median follow-up of 6.8 years (range 0.37 to 12.94 years), there was no significant difference in disease-free survival (P = 0.87) or in overall survival (P = 0.88) between the two treatment arms. The 5-year overall survival rate was 93.7% [95% confidence interval (CI) 88% to 100%] and 94.1% (95% CI 84% to 100%) in the original CISCA/VB arm and the low-dose CISCA/VB arm, respectively. The 5-year overall survival rate for the entire study population was 98% (95% CI 94% to 100%) and 88% (95% CI 76% to 100%) in the good- and intermediate-prognosis groups, respectively, as defined by the International Germ Cell Consensus Classification Group (IGCCCG). The low-dose CISCA/VB regimen resulted in significantly less neutropenic fever (P <0.001), grade 4 thrombocytopenia (P <0.03) and severe mucositis (P <0.01) than the original CISCA/VB regimen. CONCLUSIONS: CISCA/VB is highly efficient in patients with good or intermediate prognosis NSGCT according to the IGCCCG criteria. Although equivalent antitumor efficacy cannot be claimed, the low-dose CISCA/VB regimen appears to be a better mode of delivery than the original CISCA/VB regimen with respect to toxicity, since survival is comparable.

Adolescent↗

Collagen X expression in oviduct tissue during the different stages of the egg laying cycle.

The purpose of this investigation was to study the expression of type X collagen in the hen's oviduct. Type X collagen is a short-chain collagen that is present in the fibers of eggshell membranes, and there is evidence to suggest that it contributes to structural integrity. In situ hybridization and Northern blot analysis were used to study the expression of this important matrix constituent. The results demonstrated that gene expression was predominantly in the tubular gland cells of the isthmus segment of the oviduct. In contrast to observations with other matrix proteins, such as parathyroid hormone-related peptide and osteopontin, gene expression did not fluctuate with the position of the egg in the oviduct.

Animals↗

Epidemiology survey of rhegmatogenous retinal detachment in Beixinjing District, Shanghai, China.

PURPOSE: To investigate the recent incidence and related risk factors of rhegmatogenous retinal detachment (RRD) in Chinese people. METHODS: This study was an incidence survey based on data for 108,132 persons in Beixinjing District, Shanghai, China. Patients with RRD were inpatients, outpatients, and patients from the local health network. Patients with RRD were compared with control subjects who were matched by sex, age, and block of residence. Previous population data were used to estimate the whole and specific incidence of RRD. Some factors relevant to the incidence of RRD were found by comparing the patients with RRD with the control subjects. RESULTS: Between January 1996 and December 1999, 61 cases of RRD occurred. The annual incidence of RRD was 11.3 cases per 100,000 population in 1996, 14.1 cases per 100,000 population in 1997, 14.1 cases per 100,000 population in 1998, and 17.9 cases per 100,000 population in 1999. The average annual incidence was 14.4 cases per 100,000 population (95% confidence interval, 10.0-18.6). There were 29 males and 32 females with RRD. The incidence of RRD among persons older than 40 years was high, especially among those between 40 and 59 years of age. The proportion of individuals with high myopia (more than -6 diopters) was significantly higher in the patient group than in the control group (P < 0.001). CONCLUSION: The annual incidence of RRD among a local Chinese population increased over 4 years. This disease is strongly associated with high myopia and age.

Adolescent↗

Structural changes and molecular interactions of hydrophobin SC3 in solution and on a hydrophobic surface.

The hydrophobin SC3 belongs to a class of small proteins functioning in the growth and development of fungi. Its unique amphipathic property and remarkable surface activity make it interesting not only for biological studies but also for medical and industrial applications. Biophysical studies have revealed that SC3 possesses at least three distinct conformations, named "soluble-state SC3" for the protein in solution, and "alpha-helical-state SC3" and "beta-sheet-state SC3" for the different states of the protein associated at a hydrophobic-water interface. The present fluorescence study shows that the microenvironment of the dansyl-labeled N terminus of soluble-state SC3 is relatively hydrophobic, whereas it is hydrophilic for alpha-helical-state and beta-sheet-state SC3. Fluorescence collisional quenching indicates that the N terminus of soluble-state SC3 is more solvent-accessible than those of alpha-helical-state and beta-sheet-state SC3, with Stern-Volmer constants for acrylamide of 4.63, 0.02, and 0.2 M(-1) for the different states, respectively. Fluorescence resonance energy transfer measurements show that soluble-state SC3 tends to associate in solution but dissociates in TFA. Fluorescence energy transfer was eliminated by conversion of soluble-state SC3 to alpha-helical-state SC3 on a hydrophobic surface, indicating a spatial separation of the molecules in this state. By inducing the beta-sheet state, structural changes were observed, both by CD and by fluorescence, that could be fit to two exponentials with lifetimes of about 10 min and 4 h. Molecules in the beta-sheet state also underwent a slow change in spatial proximity on the hydrophobic surface, as revealed by the reappearance of fluorescence resonance energy transfer in time.

Circular Dichroism↗

Inhibition of improgan antinociception by the cannabinoid (CB)(1) antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A): lack of obligatory role for endocannabinoids acting at CB(1) receptors.

Improgan, a nonopioid antinociceptive agent, activates descending, pain-relieving mechanisms in the brain stem, but the receptor for this compound has not been identified. Because cannabinoids also activate nonopioid analgesia by a brain stem action, experiments were performed to assess the significance of cannabinoid mechanisms in improgan antinociception. The cannabinoid CB(1) antagonist N-(piperidin-1-yl)-5-(4-chloro phenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A) induced dose-dependent inhibition of improgan antinociception on the tail-flick test after i.c.v. administration in rats. The same treatments yielded comparable inhibition of cannabinoid [R-(+)-(2,3-dihydro-5-methyl-3-[(4-mor pholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl)methanone monomethanesulfonate, WIN 55,212-2] analgesia. Inhibition of improgan and WIN 55,212-2 antinociception by SR141716A was also observed in Swiss-Webster mice. Radioligand binding studies showed no appreciable affinity of improgan on rat brain, mouse brain, and human recombinant CB(1) receptors, ruling out a direct action at these sites. To test the hypothesis that CB(1) receptors indirectly participate in improgan signaling, the effects of improgan were assessed in mice with a null mutation of the CB(1) gene with and without SR141716A pretreatment. Surprisingly, improgan induced complete antinociception in both CB(1) (-/-) and wild-type control [CB(1) (+/+)] mice. Furthermore, SR141716A inhibited improgan antinociception in CB(1) (+/+) mice, but not in CB(1) (-/-) mice. Taken together, the results show that SR141716A reduces improgan antinociception, but neither cannabinoids nor CB(1) receptors seem to play an obligatory role in improgan signaling. Present and previous studies suggest that Delta(9)-tetrahydrocannabinol may act at both CB(1) and other receptors to relieve pain, but no evidence was found indicating that improgan uses either of these mechanisms. SR141716A will facilitate the study of improgan-like analgesics.

Analgesics↗