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Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 1,009 records · Page 56Linked to original sources

Lipid peroxidation in cord blood at birth: a marker of fetal hypoxia during labour.

OBJECTIVE: This prospective study examined purine metabolism in relation to free oxygen radical activity, as reflected by lipid peroxide levels in umbilical cord blood at birth. SETTING: Departments of Obstetrics and Gynaecology and of Chemical Pathology, the Chinese University of Hong Kong, Hong Kong, and Purine Research Laboratory, UMDS of Guy's and St. Thomas' Hospitals, London, UK. METHODS: Umbilical cord arterial and venous blood samples were collected from 132 singleton term deliveries for determination of hypoxanthine, xanthine, inosine, uric acid, organic hydroperoxides (OHP) and malondialdehyde. Oxygen saturation, PO2, pCO2, pH, and base excess (BE) were also measured. RESULTS: There was a significant correlation between umbilical arterial and venous levels of hypoxanthine, xanthine, inosine, uric acid and all acid-base parameters (p < 0.001). Significant arteriovenous differences were observed for all parameters with the exception of inosine, uric acid and OHP. Umbilical arterial xanthine and potassium correlated significantly with OHP, but hypoxanthine, inosine and uric acid did not. In 13 babies classified as severely asphyxiated at birth (umbilical arterial pH <7.15, BE <-8), xanthine and OHP levels were significantly elevated when compared with non-asphyxiated babies. No significant differences were observed for hypoxanthine, inosine or uric acid. CONCLUSION: The findings indicate that OHP, either in cord arterial or venous blood, is the best marker of free oxygen radical activity in the fetus, and that this correlates with other evidence of cellular hypoxia-reperfusion injury. We propose OHP is a better measure of perinatal outcome than either acid-base balance or hypoxanthine.

Adult↗

Relation of LDL size to the insulin resistance syndrome and coronary heart disease in American Indians. The Strong Heart Study.

Small, dense LDL has been shown to be associated with the insulin resistance syndrome and coronary heart disease (CHD). We examined the distribution of LDL size and phenotype within a population-based sample of American Indians to determine the relationships with prevalent CHD and to examine associations with hyperinsulinemia and other components of the insulin resistance syndrome. Data were available for 4505 men and women between 45 and 74 years of age who are members of 13 American Indian communities in three geographic areas. Diabetes, CHD, and CHD risk factors were assessed by standardized techniques, and LDL size was measured by gradient gel electrophoresis. LDL size was smaller in men than in women and in individuals with diabetes than in those without diabetes. In multivariate analysis, LDL size was significantly related to several components of the insulin resistance syndrome, including triglycerides (inversely) and HDL cholesterol (positively). Although univariate relations were positive, LDL size was not significantly related to fasting insulin concentrations or body mass index in the multivariate model. LDL size also showed no relationship to apolipoprotein E phenotype. When LDL size was compared in individuals with and without CHD, no significant differences were observed, either in nondiabetic or diabetic individuals. We conclude that LDL size is most strongly related to lipoprotein components of the insulin resistance syndrome, especially plasma triglycerides. However, in this population with low LDL, it is not related to cardiovascular disease.

Aged↗

Cholecystokinin (CCK) levels are greatly reduced in the brains but not the duodenums of Cpe(fat)/Cpe(fat) mice: a regional difference in the involvement of carboxypeptidase E (Cpe) in pro-CCK processing.

In order to assess the possible role of carboxypeptidase E (Cpe) in pro-CCK processing, tissues from the Cpe(fat)/Cpe(fat) mice were analyzed for CCK content and molecular forms using specific RIAs directed against different portions of the prohormone. Levels of amidated CCK were decreased by about 74% in whole brain of Cpe(fat)/Cpe(fat) mice in comparison to control mice, while levels of amidated CCK in intestine were only reduced by about 36%. In contrast, using an antiserum specific for CCK Gly Arg Arg, Cpe(fat)/Cpe(fat) mice brain had about 13-fold higher levels of this peptide relative to controls, while levels were identical in mutant and control duodenal tissue. This study demonstrates a regional difference in the involvement of Cpe in pro-CCK processing. The accumulation of CCK Gly Arg Arg in Cpe(fat)/Cpe(fat) brains provides definitive proof that the dibasic cleavage of the carboxyl terminus of pro CCK occurs on the carboxyl terminal of the dibasic, between the Arg and Ser as well as confirming that amidated CCK 8 in brain originates from CCK 8 Gly Arg Arg rather than from larger amidated peptides like CCK 22 or CCK 33. The Cpe(fat)/Cpe(fat) mouse phenotype obviously involves multiple endocrine defects, however, it is tempting to speculate that this severe CNS deficiency in CCK 8 may be related to the adult-onset obesity seen in this mutant mouse.

Animals↗

Altered expression of the alpha7beta1 integrin in human and murine muscular dystrophies.

The alpha7beta1 integrin is the primary laminin receptor on skeletal myoblasts and adult myofibers. It has distinct functions during muscle development and contributes to muscle structural integrity. We have studied this integrin in cases where expression of dystrophin or laminin are compromised. Immunofluorescence demonstrates an increase in alpha7beta1 in patients with Duchenne muscular dystrophy and in mdx mice that lack dystrophin. Analysis of RNA from mdx mice and from patients with Duchenne and Becker muscular dystrophies indicates that the increase in the alpha7beta1 integrin is regulated at the level of alpha7 gene transcription. In contrast, the levels of alpha7beta1 integrin are severely diminished in patients with laminin alpha2 chain congenital dystrophy muscular dystrophy and in dy/dy mice that also do not make the alpha2 laminin chain. Analysis of RNA from the hindlimbs of dy/dy mice demonstrated that in the absence of laminin alpha7 gene transcription is inhibited and limited to specific alternatively spliced isoforms. We suggest that the increased expression of alpha7beta1 integrin in the absence of dystrophin compensates for the reduced dystrophin-mediated linkage of fibers with the basal lamina and modulates the development of pathology associated with these diseases. The decrease in alpha7beta1 integrin and its transcripts in the absence of laminin likely contributes to the severe myopathy that results from laminin alpha2 chain deficiency and suggests that laminin-2 regulates expression of the alpha7 integrin gene. The role of the alpha7beta1 integrin in muscle integrity also suggests that compromised expression of this receptor may underlie as yet undefined myopathies.

Adult↗

Interaction of arenastatin A with porcine brain tubulin.

Arenastatin A, isolated from the Okinawan marine sponge Dysidea arenaria, is an antimitotic depsipeptide containing a 16-membered ring. Interaction of the compound with tubulin was investigated by the use of [3H]arenastatin A and other microtubule disruptors. Scatchard analysis indicated the presence of one binding site for arenastatin A per tubulin heterodimer with a dissociation constant (Kd) of 1.8 x 10(-6) M. Rhizoxin was a competitive inhibitor of arenastatin A binding, and vinblastine also inhibited arenastatin A binding in a partially competitive manner. Arenastatin A had no inhibitory effect on colchicine binding to tubulin.

Animals↗

Biomaterial particle phagocytosis by bone-resorbing osteoclasts.

Abundant implant-derived biomaterial wear particles are generated in aseptic loosening and are deposited in periprosthetic tissues in which they are phagocytosed by mononuclear and multinucleated macrophage-like cells. It has been stated that the multinucleated cells which contain wear particles are not bone-resorbing osteoclasts. To investigate the validity of this claim we isolated human osteoclasts from giant-cell tumours of bone and rat osteoclasts from long bones. These were cultured on glass coverslips and on cortical bone slices in the presence of particles of latex, PMMA and titanium. Osteoclast phagocytosis of these particle types was shown by light microscopy, energy-dispersive X-ray analysis and SEM. Giant cells containing phagocytosed particles were seen to be associated with the formation of resorption lacunae. Osteoclasts containing particles were also calcitonin-receptor-positive and showed an inhibitory response to calcitonin. Our findings demonstrate that osteoclasts are capable of phagocytosing particles of a wide range of size, including particles of polymeric and metallic biomaterials found in periprosthetic tissues, and that after particle phagocytosis, they remain fully functional, hormone-responsive, bone-resorbing cells.

Bone Resorption↗

Dicistronic LacZ and alkaline phosphatase reporter constructs permit simultaneous histological analysis of expression from multiple transgenes.

We report here the development of convenient dicistronic transgenic markers for the rapid and efficient simultaneous analysis of transgene activity in transgenic mice. Two sensitive histological markers, the beta-galactosidase (beta-gal)-encoding lacZ gene and the human placental alkaline phosphatase (hpAP) gene, have been fused to the internal ribosome entry sequence (IRES) from the encephalomyocarditis virus, which directs efficient mRNA cap-independent entry of the translation apparatus in mammalian cells. The IRES permits efficient translation of either lacZ or hpAP when placed anywhere within transgene exonic sequences, including both 5' and 3' untranslated regions. In addition, the production of constructs for transgenic analysis of DNA regulatory elements is greatly facilitated with IRES-lacZ or IRES-hpAP, since the IRES relieves the need for complicated in frame transgene protein fusions to produce a functional beta-gal or hpAP protein.

Alkaline Phosphatase↗

Oxygen free radical activity in the second stage of labor.

OBJECTIVE: To assess fetal cellular injury arising from oxygen free radical activity in relation to the duration of the second stage of labor. PATIENTS AND METHODS: Cord arterial pH, malondialdehyde and organic hydroperoxides levels were determined following vaginal delivery of 326 term singleton pregnancies. Of these, 35 (11%) received epidural analgesia. The length of the second stage was recorded from the time of full dilatation to delivery. RESULTS: Arterial cord pH, malondialdehyde and organic hydroperoxides were significantly correlated with duration of second stage of labor (r=-0.4492; r=0.2542; r=0.2244; respectively, p<0.001). The association of lipid peroxidation products with second stage duration was independent of cord pH. This correlation was unchanged when cases of operative delivery were excluded. However, the relationship lost statistical significance amongst cases who received epidurals. CONCLUSIONS: The duration of the second stage is correlated with raised reactive oxygen species-derived lipid peroxidation products. Caution should be exercised in the management of prolonged second stage of labor.

Adolescent↗

Expression of c-Myc, TGF-alpha and EGF-receptor in sporadic medullary thyroid carcinoma.

In 20 patients with sporadic medullary thyroid carcinoma (MTC), immuno-histochemistry was used to localize the expression of the c-Myc oncoprotein, transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) and these three markers were analysed regarding their relation to histopathological and histochemical variables of the tumours. The detection rates of c-Myc, TGF-alpha and EGFR were 90%, 90% and 95% respectively. Concomitant demonstration of the markers was reflected in significant associations (correlation factor between TGF-alpha and EGFR was 0.93, p < 0.001). The markers were almost invariably located within the cytoplasm, which might suggest their crucial role in growth regulation and cell differentiation; this seems especially true of TGF-alpha and EGFR. The different markers showed no relation to either histopathological or histochemical variables (tumour behaviour, tumour size, tumour cell type). The prominent co-expression of c-Myc, TGF-alpha and EGFR proteins indicates that in MTC these factors might be of importance for tumour cell proliferation via autocrine growth stimulation.

Adolescent↗

Kidney extracts from spontaneously hypertensive rats (SHR) have greater dopamine 1A receptor RNA-binding activity than extracts from normotensive Wistar-Kyoto (WKY) rats.

Rat kidney extracts contain a 52 kDa protein that binds to the 3' untranslated region of the dopamine 1A (D1A) receptor mRNA at a 243 base-long cis element starting at the stop codon and ending approximately 220 bases upstream of an AUUUA-rich region. The D1A receptor RNA-binding protein (D1A-BP) is redox-sensitive; free sulfhydryl groups on the protein are required for binding. Kidney extracts from SHR have significantly more D1A-BP activity than extracts from WKY rats. When kidney extracts were tested for binding to an 80-base RNA containing four AUUUA repeats, there was also greater binding activity in extracts from SHR. These increases are at least partly specific because there was no difference in catalase RNA-binding protein activity between the two rat strains. These data suggest D1A-BP and AUUUA-binding protein may play a role in posttranscriptional regulation of the D1A receptor in the hypertensive rat.

Animals↗

Effects of anastomoses on solute transcapillary exchange in countercurrent systems.

OBJECTIVE: To investigate effects of anastomoses between the descending vasa recta (DVR) and the ascending vasa recta (AVR) on the distribution of small solutes in the interstitial fluid of the renal medulla. METHODS: Countercurrent capillary loops, surrounded by a secretory epithelium, were used to model microvessels in the renal medulla. Anastomoses between the DVR and AVR were modeled as a decrease in cross-sectional area of the vessels and a decrease in flow velocity from the base to the tip of the capillary loop. When experimental data were used to evaluate parameters of the model, it was seen that diffusive transport of solute in the axial direction of the capillary was negligible, and the equations could be greatly simplified. RESULTS: General formulae of the solute concentration distribution were derived for different degrees of shunting between the two limbs of the capillary loop. Analytical solutions for the steady-state solute distribution were obtained when the sizes of capillaries and flows in them were assumed to decrease linearly with the distance from the base to the tip of the capillary loop. When the effects of reduction in the size of the limbs were compared with the effects of reduction of flow velocities on solute distribution, it was found that, in the presence of anastomoses, change in flow velocity increases the axial gradient of the solute concentration more than change in the cross-sectional area. The combined effects of a decrease in flow velocity and cross-sectional area can easily double the axial gradient of the solute concentration for a modest degree of anastomotic shunting. CONCLUSIONS: In this study, we separated effects of anastomotic flow between the DVR and AVR from other factors affecting the complicated countercurrent solute exchanges in the renal medulla. Results from the model show that anastomoses increase the solute concentration in the medullary interstitium and also the axial gradient of the solute concentration there.

Animals↗

[Efficacy of prostaglandin E1 in treatment of cor pulmonale patients with heart failure].

OBJECTIVE: To investigate the effects of prostaglandin E1 (PGE1) by intravenous drip in cor pulmonale patients with heart failure. METHODS: Thirty caseas of cor pulmonale with heart failure were treated with PGE1 at a dose of 200 micrograms.d-1 for 5 days and in 30 patients with cor pulmonale heart failure (no PGE1) and in 20 healthy subjects as controls. The level of serum endogenous digoxin-like factor (EDF), serum lipoid superoxide (LPO), serum superoxide dismutase (SOD) and blood PaO2, PaCO2 were determined. Their symptoms and signs were observed before and after treatment. RESULTS: The level of serum EDF, LPO were significantly increased (P < 0.001) and serum SOD was significantly decreased (P < 0.001) in PGE1 group and controls group (no PGE1) as compared with healthy subjects. In PGE1 group the level of serum EDF, LPO were markedly decreased (P < 0.001), and serum SOD was markedly elevated (P < 0.001), and their symptoms, signs and blood gas parameters had noteworthyly improved (P < 0.01-0.001). But in the control group (no PGE1) the level of serum EDF, LPO, SOD, blood gas parameters and their symptoms and signs, showed no significant difference (P > 0.05). CONCLUSIONS: PGE1 is effective in therapy of cor pulmonale with heart failure. Treatment with PGE1 shows more significant benefits in cor pulmonale patients with heart failure.

Aged↗

Molecular modeling of voltage-gated potassium channel pore.

AIM: To build a structure model for the pore of voltage-gated Shaker potassium channel and examine its validity. METHODS: (1) Structural restraints were derived from experimental and theoretical studies; (2) An initial structural motif satisfying the derived restraints was first constructed, and further refined by restrained molecular mechanics; (3) The quality of the model was judged by the criterion that whether it could clarify molecular mechanisms of channel functions and explain the known experimental facts. RESULTS: (1) A computer pore structure was proposed, in which the residues within signature sequence (corresponding to Shaker 439-446) dipped into the membrane and formed the narrow part of the pore in a non-periodic conformation, while the other residues in the P region constituted the outer mouth of the pore; (2) The ion selectivity was achieved through cation-pi orbital interaction mechanism at position 445 and oxygen cage mechanism at position 447; (3) Different binding modes led to different affinity of CTX and AgTx2 to channel; and (4) The inside of pore was dominated by negative electrostatic potential. CONCLUSION: The model proposed was consistent with the derived restraints from the experimental results.

Amino Acid Sequence↗

[Clinical application of highly selected embolotherapy via external carotid artery in craniofacial diseases].

Forty-three cases of hypervascularized tumors and vascular lesions supplied by external carotid artery were treated by endovascular embolization. The results showed that hypervascularized tumor's bleeding markedly reduced and its volume diminished during operation; vascular lesions were cured or improved after embolization. The choice of embolic materials and technical essentials were discussed.

Adolescent↗

[Clinical evaluation on parenteral nutrition in neonatal disease].

Thirty cases of neonatal disease were treated with parenteral nutrition (PN) as an adjuvant treatment and compared with the control group (n = 30). The body weight and plasma albumin increased remarkably in the PN group (P < 0.01, P < 0.05). No significant metabolic complication was occurred (P > 0.05). PN proved to be a safe and effective approach for neonatal patients, in which nutritional admixture components were adjusted day by day according to gestational age, body weight, disease course and monitor indexes to match the actual gastric intestinal tract function.

Humans↗

[Study on effects of Codonopsis eupolyphaga anti-obesity powder in mice with nutritive obesity].

OBJECTIVE: To observe the effects of Codonopsis Eupolyphaga anti-obesity powder(CEAOP) in mice with nutritive obesity. METHODS: CEAOP 0.5-2.5 g/kg was given to mice for 4 weeks and its effect was observed. RESULTS: CEAOP could significantly reduce the Lee's index, weight of fat cushion and fat index, lower the blood levels of total cholesterol, triglyceride and blood glucose, but influence neither the calories and quantity of food intake, nor the endurance against anoxia and fatigue, the property of stool was not changed at all. CONCLUSIONS: The anti-obesity effect of CEAOP was similar to Fenfluramini but without influence on appetite and bowel movement, tolerance against anoxia and fatigue. The mechanism of the anti-obesity might be related with its metabolism regulating actions on lipids and glucose.

Animals↗