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Biomedical subjects

D Wang

Publications and source records attributed to D Wang.

At least 181 records · Page 10Linked to original sources
PubMed2001

Systematic review of the impact of beta blockers on mortality and hospital admissions in heart failure.

Heart failure is a common condition that carries a high burden of mortality and morbidity. Several randomised trials have evaluated the effects of beta blockers in heart failure. This paper gives a systematic overview of published randomised trials of beta blockers in heart failure using standard methods. In all, 22 randomised controlled trials were identified with a total of 10480 patients, and an average of 11 months of treatment. The average age was 61 years and 4% were female. Most studies excluded patients with severe heart failure. Death rates in patients randomised to receive beta blockers compared to controls were 458/5657 (8.0%) and 635/4951 (12.8%) respectively, odds ratio 0.63, 95% CI 0.55-0.72, P<0.00001. Similar reductions were observed for hospital admissions for worsening heart failure (11.3 vs. 17.1%, respectively, odds ratio 0.63) and for the composite outcome of death or heart-failure hospital admission (19.4 vs. 26.9%, respectively, odds ratio 0.66). These results show that beta blockers reduce the risk of mortality or the need for heart-failure hospital admission by approximately one third. Absolute reductions of 5-6% in event rates were observed over approximately 1 year of treatment period. These important benefits should be implemented as a priority, since treatment with beta blockers is inexpensive and heart failure carries a high risk of death and disability. Further information on the effect of beta blockers in elderly patients and women would be helpful.

Adrenergic beta-Antagonists↗
PubMed2001

Identification of the type II Na(+)-Pi cotransporter (Npt2) in the osteoclast and the skeletal phenotype of Npt2-/- mice.

We previously reported that a type II sodium phosphate (Na(+)-Pi) cotransporter (Npt2) protein is expressed in osteoclasts and that Pi limitation decreases osteoclast-mediated bone resorption in vitro. We also demonstrated that mice homozygous for the disrupted Npt2 gene (Npt2-/-) exhibit a unique age-dependent bone phenotype that is associated with significant hypophosphatemia. In the present study, we sought to identify the Npt2 cDNA in mouse osteoclasts and characterize the impact of Npt2 gene ablation on osteoclast function and bone histomorphometry. We demonstrate that the osteoclast Npt2 cDNA sequence is identical to that of the proximal renal tubule and, thus, not an isoform or splice variant thereof. Histomorphometric analysis revealed that, at 25 days of age, Npt2-/- mice exhibited a reduction in osteoclast number and eroded perimeters, relative to wild-type mice. Moreover, although the number of metaphyseal trabeculae was reduced in 25-day-old Npt2-/- mice, trabecular bone volume was normal due to increased trabecular width. At 115 days of age, the decrease in osteoclast index persisted in Npt2-/- mice relative to wild-type littermates. However, mineralizing and osteoblast surfaces and bone formation rates were increased, and, although trabecular number was still reduced, trabecular bone volume was higher than that of wild-type mice. These data demonstrate a link between osteoclast activity and trabecular development in young Npt2-/- mice, and suggest that an age-related adaptation to Npt2 deficiency is apparent in osteoclast and osteoblast function and bone formation.

Animals↗
PubMed2001

Fine-scale mapping using Hardy-Weinberg disequilibrium.

Hardy-Weinberg disequilibrium (HWD) among affected individuals has recently been proposed for fine-scale mapping of disease susceptibility genes. We investigate the statistical properties of several available HWD measures and develop a new HWD measure J for fine-scale mapping. It is shown both theoretically and through simulations that the available HWD measures depend not only on the genetic distance between the marker locus of interest and the disease susceptibility locus, but also on the allele frequencies at the marker locus. On the contrary, the new measure is not affected by the allele frequencies at the marker locus under the following assumptions: (a) there is initial complete linkage disequilibrium between the marker and the disease loci, (b) there are no new mutations at the marker and the disease loci, and (c) the population under study is large. We develop a novel method to estimate the location of the disease susceptibility gene based on the HWD measure J. The estimator is robust to low mutation rates at the marker and the disease loci. We compare the standard error of the estimated disease gene loci using P excess for case-control studies with the standard error using J for case-only studies under various disease models. The newly developed method is successfully applied to a data set on hereditary haemochromatosis (HH).

Analysis of Variance↗
PubMed2001

Analysis of glycosidically bound aroma precursors in tea leaves. 2. Changes in glycoside contents and glycosidase activities in tea leaves during the black tea manufacturing process.

Glycosides are known to be precursors of the alcoholic aroma compounds of black tea. They are hydrolyzed by endogenous glycosidases during the manufacturing process. Changes in the amounts of these glycosides during the manufacturing process were investigated by using a capillary gas chromatographic--mass spectrometric analysis after trifluoroacetyl derivatization of the tea glycosidic fractions. Primeverosides were 3-fold more abundant than glucosides in fresh leaves, but they decreased greatly during the manufacturing process, especially during the stage of rolling. After the final stage of fermentation, primeverosides had almost disappeared, whereas glucosides were substantially unchanged. These results show that hydrolysis of the glycosides mainly occurred during the stage of rolling and confirm that primeverosides are the main black tea aroma precursors. This was also supported by the changes in the glycosidase activities in tea leaves. The glycosidase activities remained at a high level during withering but decreased drastically after rolling.

Fermentation↗
PubMed2001

Analysis of glycosidically bound aroma precursors in tea leaves. 3. Change in the glycoside content of tea leaves during the oolong tea manufacturing process.

A direct qualitative and quantitative determination of the glycosides of tea aroma compounds at the four stages of the oolong tea manufacturing process (plucking, solar withering, indoor withering, and oolong tea product) was carried out by a capillary gas chromatographic-mass spectrometric analysis after trifluoroacetyl derivatization of the glycosidic fractions. Sixteen glucosides and primeverosides were identified and quantified in cv. Chin-shin-oolong and cv. Chinhsuan-oolong. A comparison of the glycosides in dried fresh leaves between the two cultivars showed significant differences. During the manufacturing process, the amounts of most of these glycosides increased from the solar-withering stage, reaching the highest level at the final stage of oolong tea production. It was noted that no glycoside decreased in its content during the manufacturing process, this being quite different from the manufacture of black tea. In addition, the contents of these alcoholic aroma compounds in the free aroma concentrate from each cultivar remained almost unchanged or slightly decreased, and they constituted only about 12 and 17% in amount of the whole oolong tea aroma compounds. However, jasmine lactone and indole were markedly higher in the final oolong tea products.

Chromatography, Gas↗
PubMed2001

A new insect neurotoxin AngP1 with analgesic effect from the scorpion Buthus martensii Karsch: purification and characterization.

An insect toxin named BmK AngP1 was purified from the venom of the scorpion Buthus martensii Karsch (BmK). It also shows an evident analgesic effect on mice, but is interestingly devoid of mammalian toxicity. Bioassay showed that the CPU value of AngP1 was 0.01 microg/body ( approximately 30 mg) for the excitatory insect toxicity and 43.0% inhibition efficiency for analgesia at a dose of 5 mg/kg. However, even at the dosage of 10 mg/kg no detectable toxicity on mice could be found. The isoelectric point (pI) value for AngP1 was 4.0, and its molecular mass analyzed by MALDI-TOF MS was 8141.0. The first 15 N-terminal residues of AngP1 were determined by Edman degradation and showed high similarity to that of other excitatory scorpion insect toxins. The circular dichroism spectroscopy measured on a JASCO J-720 system showed that there were 10.4% alpha-helix, 46.2% beta-strand and 14.1% turn structure in this peptide. Under two conditions single crystals of AngP1 were obtained.

Amino Acid Sequence↗
PubMed2001

Angiostatin enhances B7.1-mediated cancer immunotherapy independently of effects on vascular endothelial growth factor expression.

Tumors must develop an adequate vascular network to meet their increasing demands for nutrition and oxygen. Angiostatin, a multiple kringle (1-4)-containing fragment of plasminogen, is an effective natural inhibitor of tumor angiogenesis. Here we show that gene transfer of angiostatin into small (0.1 cm in diameter) solid EL-4 lymphomas established in syngeneic C57BL/6 mice led to reduced tumor angiogenesis and weak inhibition of tumor growth. In contrast, when angiostatin gene therapy was preceded by in situ gene transfer of the T-cell costimulator B7.1, large (0.4 cm in diameter) tumors were rapidly and completely eradicated, whereas B7.1 and angiostatin monotherapies were ineffective. Combined gene transfer of B7.1 and angiostatin generated potent systemic antitumor immunity that was effective in eradicating a systemic challenge of 10(7) EL-4 cells. Gene transfer of angiostatin expression plasmids led to overexpression of angiostatin in tumors, increased apoptosis of tumor cells, and decreased density of tumor blood vessels, which may allow the immune system to overcome tumor immune resistance. The latter effects were not the result of a decrease in vascular endothelial growth factor expression, as tumoral vascular endothelial growth factor expression increased slightly after angiostatin gene transfer, presumably in response to increasing hypoxia. These results suggest that combining immunogene therapy with a vascular attack by angiostatin is a particularly effective approach for eliciting antitumor immunity.

Angiostatins↗
PubMed2001

Gene transfer of antisense hypoxia inducible factor-1 alpha enhances the therapeutic efficacy of cancer immunotherapy.

Solid tumors meet their demands for nascent blood vessels and increased glycolysis, to combat hypoxia, by activating multiple genes involved in angiogenesis and glucose metabolism. Hypoxia inducible factor-1 (HIF-1) is a constitutively expressed basic helix-loop-helix transcription factor, formed by the assembly of HIF-1alpha and HIF-1beta (Arnt), that is stablized in response to hypoxia, and rapidly degraded under normoxic conditions. It activates the transcription of genes important for maintaining oxygen homeostasis. Here, we demonstrate that engineered down-regulation of HIF-1alpha by intratumoral gene transfer of an antisense HIF-1alpha plasmid leads to the down-regulation of VEGF, and decreased tumor microvessel density. Antisense HIF-1alpha monotherapy resulted in the complete and permanent rejection of small (0.1 cm in diameter) EL-4 tumors, which is unusual for an anti-angiogenic agent where transient suppression of tumor growth is the norm. It induced NK cell-dependent rejection of tumors, but failed to stimulate systemic T cell-mediated anti-tumor immunity, and synergized with B7-1-mediated immunotherapy to cause the NK cell and CD8 T cell-dependent rejection of larger EL-4 tumors (0.4 cm in diameter) that were refractory to monotherapies. Mice cured of their tumors by combination therapy resisted a rechallenge with parental tumor cells, indicating systemic antitumor immunity had been achieved. In summary, whilst intensive investigations are in progress to target the many HIF-1 effectors, the results herein indicate that blocking hypoxia-inducible pathways and enhancing NK-mediated antitumor immunity by targeting HIF-1 itself may be advantageous, especially when combined with cancer immunotherapy.

Animals↗
PubMed2001

Development of an analytical technique and stability evaluation of 143 C3-C12 volatile organic compounds in Summa canisters by gas chromatography-mass spectrometry.

A technique using Summa canisters with cryogenic preconcentration and gas chromatographic-mass spectrometric (GC-MS) detection was developed to determine 143 C3-C12 volatile organic compounds (VOCs) including alkanes, alkenes, aromatics and halohydrocarbons in ambient and indoor air. The method detection limits and practical quantification limits were sensitive at 0.02 and 0.10 ppbv, respectively, and the method precision and accuracy were also satisfactory. The stability of C3-C12 VOC standards at ppbv levels under elevated pressure in canisters was assessed over various time intervals (from 1 week to 4 months after preparation) and most of the compounds were found to be acceptably stable with a mean recovery of 85.6 +/- 9.9% during the course of a 4-month study. However, a small fraction (approximately 6%) of the compounds, including two halohydrocarbons (bromotrichloromethane and benzyl chloride) and six alkenes (2-methylbuta-1,3-diene (isoprene), cis-4-methylpent-2-ene, cis-3-methylpent-2-ene, hept-1-ene, oct-1-ene and styrene) displayed relatively low recoveries in the range 34.6-67.9%. The loss of these compounds is most probably caused by their physical adherence to the active sites of the canister surface, chemical decomposition and/or reactions with other species. The results indicated that one must be cautious in attempting to measure these compounds owing to their instability in canisters. Overall, this analytical technique, which has been used for the determination of the VOCs under study in the toxic air pollutant monitoring network administered by the HKSAR Government, was amenable to the measurement of airborne VOCs collected both outside and inside a semi-confined car park in the present study.

Air Pollutants↗
PubMed2001

Artificial ion channels formed by a synthetic cyclic peptide.

A new cyclic peptide 1 having an (LLLD)3 configuration pattern was designed that is capable of forming artificial transmembrane ion channels by self-assembly of planar peptide rings, with hydrophilic groups arrayed in the interior of the channel. Ion permeability in the presence of the synthetic peptide 1, cyclo[-Trp-Dap-Leu-D-Ala-Trp-Ser-Val-D-Ala-Trp-Ser-Ile-Gly-] (Dap: L-diaminopropionic acid), was observed in lipid bilayer membranes. The pH dependence of ionic conductance showed that the beta-amino group of Dap may play a role in the conductance of the peptide channels. Fourier-transform infrared and circular dichroism data imply that, in a membrane, a stack of cyclic peptides is formed in which the inter peptide H bonds form a kind of beta-structure analogous to that in the gramicidin A dimer and distinct from the H-bonding pattern of the beta-barrels.

Circular Dichroism↗
PubMed2001

The lung is the major site that produces nitric oxide to induce acute pulmonary oedema in endotoxin shock.

1. The present study was undertaken to determine the locus of nitric oxide (NO) production that is toxic to the lung and produces acute pulmonary oedema in endotoxin shock, to examine and compare the effects of changes in lung perfusate on endotoxin-induced pulmonary oedema (EPE) and to evaluate the involvement of constitutive and inducible NO synthase (cNOS and iNOS, respectively). 2. Experiments were designed to induce septic shock in anaesthetized rats with the administration of Escherichia coli lipopolysaccharide (LPS). Exhaled NO, lung weight (LW)/bodyweight (BW) ratio, LW gain (LWG) and lung histology were measured and observed to determine the degree of EPE 4 h following LPS. The EPE was compared between groups in which LPS had been injected either into the systemic circulation or into the isolated perfused lung. The lung perfusate was altered from whole blood to physiological saline solution (PSS) with 6% albumin to test whether different lung perfusions affected EPE. Pretreatment with various NOS inhibitors was undertaken 10 min before LPS to investigate the contribution of cNOS and iNOS to the observed effects. 3. Endotoxin caused profound systemic hypotension, but little change in pulmonary arterial pressure. The extent of EPE was not different between that induced by systemic injection and that following administration to isolated lungs preparations. Replacement of whole blood with PSS greatly attenuated (P < 0.05) EPE. In blood-perfused lungs, pretreatment with NOS inhibitors, such as Nomega-nitro-L-arginine methyl ester, aminoguanidine and dexamethasone, significantly prevented EPE (P < 0.05). 4. The major site of NO production through the whole blood is in the lung. The NO production mediated by the iNOS system is toxic to the endothelium in the pulmonary microvasculature. Inhalation of NO for patients with sepsis may be used with clinical caution. Therapeutic consideration of lung extracorporeal perfusion with PSS and pharmacological pretreatment with iNOS inhibitors may be warranted.

Animals↗
PubMed2001

Inverse agonists and neutral antagonists at mu opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence.

The mu opioid receptor, MOR, displays spontaneous agonist-independent (basal) G protein coupling in vitro. To determine whether basal MOR signaling contributes to narcotic dependence, antagonists were tested for intrinsic effects on basal MOR signaling in vitro and in vivo, before and after morphine pretreatment. Intrinsic effects of MOR ligands were tested by measuring GTPgammaS binding to cell membranes and cAMP levels in intact cells. beta-CNA, C-CAM, BNTX, and nalmefene were identified as inverse agonists (suppressing basal MOR signaling). Naloxone and naltrexone were neutral antagonists (not affecting basal signaling) in untreated cells, whereas inverse agonistic effects became apparent only after morphine pretreatment. In contrast, 6alpha- and 6beta-naltrexol and -naloxol, and 6beta-naltrexamine were neutral antagonists regardless of morphine pretreatment. In an acute and chronic mouse model of morphine-induced dependence, 6beta-naltrexol caused significantly reduced withdrawal jumping compared to naloxone and naltrexone, at doses effective in blocking morphine antinociception. This supports the hypothesis that naloxone-induced withdrawal symptoms result at least in part from suppression of basal signaling activity of MOR in morphine-dependent animals. Neutral antagonists have promise in treatment of narcotic addiction.

Analgesics, Opioid↗
PubMed2001

Changes in the inferior alveolar nerve after mandibular lengthening with different rates of distraction.

PURPOSE: This study investigated the changes in the inferior alveolar nerve after mandibular lengthening with different rates of distraction. MATERIALS AND METHODS: Bilateral mandibular corticotomies were performed in 8 goats. The mandibles in 6 goats were lengthened 10 mm using a custom-made distractor with 2 different rates of distraction (1 mm/d [n = 3] and 2 mm/d [n = 3]); the other 2 nondistracted mandibles served as a control. The goats with distracted mandibles were killed at 2 weeks after completion of distraction. The inferior alveolar nerve specimens from all animals were harvested and processed for histologic and ultrastructural evaluation. RESULTS: The mandibles were lengthened successfully in the distracted animals. Morphologic changes in the inferior alveolar nerves were observed when compared with the nondistracted controls. Moreover, signs of nerve degeneration, such as demyelination, axonal swelling, axoplasmic darking, and decrease in the number of axons, were more extensive and prominent in those nerves distracted at a rate of 2 mm/d. CONCLUSIONS: Degenerative changes in the inferior alveolar nerve occur after mandibular lengthening by distraction osteogenesis. The distraction rate of 1 mm/d appears to be tolerable and safe for the inferior alveolar nerve, but rapid distraction may cause serious degeneration.

Animals↗
PubMed2001

Oestrogen receptor beta expression and depth of myometrial invasion in human endometrial cancer.

We assessed the relative expression of oestrogen receptor (ER)alpha and oestrogen receptor (ER)beta mRNAs in 36 human endometrial cancers using a multiplex polymerase chain reaction (PCR). To determine whether or not the expression of ER subtypes in endometrial cancers is associated with clinicopathological parameters, we examined correlations between ER subtypes and age, tumour grade and depth of myometrial invasion. Using multiple regression analysis, myometrial invasion showed a significant correlation with ER-beta: ER-alpha ratio (r = 0.54, P = 0.0007). The ER-beta:ER-alpha ratio was high in advanced invasive carcinoma. Western blotting analysis showed that ER-beta proteins were highly expressed in comparison with ER-alpha proteins in endometrial cancer with severe myometrial invasion. Our results suggest that ER-beta is important in the progression of myometrial invasion.

Adult↗
PubMed2001

Association of the mitochondrial DNA 5178A/C polymorphism with maternal inheritance and onset of type 2 diabetes in Japanese patients.

The mitochondrial DNA 5178A/C (mt5178A/C) polymorphism is associated with longevity and adult onset diseases. We investigated an association of the mt5178A/C polymorphism with the occurrence and clinical features of type 2 diabetes. Two hundred and seventy Japanese patients with type 2 diabetes (181 men and 89 women) and 254 control subjects without diabetes were studied. Patients with mutations at position 3243 in the mitochondrial DNA were excluded. Genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism method. Various clinical features including age at disease onset were compared between the patients with the mt5178A and mt5178C alleles. Mt5178C was observed more frequently in patients with type 2 diabetes than in control subjects (65.9% vs 57.9%, P = 0.058). Clear information about the maternal history of diabetes was obtained from 233 diabetic patients. Patients with a maternal history of diabetes carried the mt5178C allele (58/75, 77.3%) more frequently than did patients without a maternal history of diabetes (100/158, 63.3%; P = 0.032) and control subjects (57.9%; P = 0.002). The mean age at onset of diabetes was significantly lower in patients with mt5178C (47.6 +/- 11.4 years) than in patients with mt5178A (51.5 +/- 10.0 years; P = 0.0073). The mt5178A/C polymorphism may be associated with maternal inheritance of type 2 diabetes and may influence the age at onset through deterioration of mitochondrial function.

Adolescent↗
PubMed2001

Osteoblastic proliferation stimulating activity of Psoralea corylifolia extracts and two of its flavonoids.

Psoralea corylifolia L. fruit extracts exhibited osteoblastic proliferation stimulating activity in UMR106 cell line cultured in vitro. The flavonoids of corylin and bavachin were isolated and identified as active principles by activity-guided fractionation. The results suggested that Psoralea corylifolia L. fruit extracts and corylin and bavachin might stimulate bone formation or have potential activity against osteoporosis.

Cell Division↗