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Biomedical subjects

Y Du

Publications and source records attributed to Y Du.

At least 109 records · Page 6Linked to original sources
PubMed1999

[A gene analysis of familial lipoprotein lipase deficiency in China].

OBJECTIVE: To investigate the gene mutation of lipoprotein lipase(LPL) of familial LPL deficiency in China. METHODS: The DNA sequencing of LPL gene of the patients was performed with the dideoxy method based on the polymerase chain reaction amplification using the genomic DNA as a template. RESULTS: It was identified that a missense mutation in exon 6 of LPL gene (6G(979)-->A) resulted in the substitution of Glu(242) by Lys in a heterozygous state. CONCLUSION: The missense mutation of LPL may play a key role in the decrease of LPL activity. This is the first report about the gene mutation of LPL at this site in familial LPL deficiency. Moreover, it contributes to the elucidation of the pathophysiological mechanisms of atherosclerosis and some metabolic diseases.

Adult↗
PubMed1999

Oviposition responses of gravid Culex quinquefasciatus and Culex tarsalis to bulrush (Schoenoplectus acutus) infusions.

Laboratory bioassays demonstrated that fermented infusions of dried bulrushes (Schoenoplectus acutus) strongly attracted and stimulated oviposition by gravid female Culex quinquefasciatus and Culex tarsalis. The responses of the 2 species varied with the concentration and method of preparation of the infusions, with responses generally increasing with increasing concentration. No major differences were found in the responses of either species to infusions prepared with bulrushes alone, or with bulrushes plus lactalbumin hydrolysate and brewer's yeast. Infusions remained more attractive than distilled water controls to both species for up to 8 wk. Field tests corroborated the results from the laboratory bioassays. Culex quinquefasciatus, Cx. tarsalis, and Cx. stigmatosoma egg rafts were collected from water pan traps baited with bulrush infusions. A few Culiseta incidens eggs also were collected. In multiple-choice tests using gravid female or egg traps, Cx. quinquefasciatus preferred the most concentrated bulrush infusions, whereas Cx. tarsalis preferred intermediate concentrations. Female Cx. stigmatosoma and Culiseta incidens also were attracted. Overall, these results may provide new leads towards developing synthetic chemical baits to attract bloodfed mosquitoes.

Animals↗
PubMed1999

[Study on Cao Xi's medical works].

Cao Xi is a famous physician of the Wei - Jin Dynasties. His medical works had been lost since the Song Dynasty. But there are some fragments of its text retained in some extant medical literatures. Through analysing these lost remained texts, Cao Xi's medical works are systematically studied. Some errors about Cao Xi's medical works are thus corrected.

China↗
PubMed1999

[Purification and identification of pili of Vibrio cholera O139].

To provide the base of manufacturing V. cholera O139 subunit vaccine, purification and identification methods of V. cholera O139 Toxin-coregulated pili (TCP) were studied. The results showed the optimal expressing condition of TCP was in AKI or CFA medium, at 30 C for 24-36 h with stationary cultivation. The molecular weight of the TCP subunit protein measured by sodium dodecyl sulfate-poly acrylamide gel electrophoresis was about 20.5 kd. By using mouse anti-TCP monoclone antibody and sheep anti-mouse IgG-HRP antibody, the TCP was confirmed by dot blot immunoassay. Rabbit immune serum of TCP purified from O139 strain agglutinated both O139 biotype and El Tor biotype Vibrio cholera strains. These indicate that TCP may be an effective and protective antigen to conduct the preparation of V. cholera vaccine.

Animals↗
PubMed1998

The NF-kappaB/Rel family of proteins mediates Abeta-induced neurotoxicity and glial activation.

The beta-amyloid peptide (Abeta) is deposited in neuritic plaques which are characteristic features of Alzheimer's disease (AD). Prominent neurodegeneration and glial activation occurs around these plaques leading to the hypothesis that Abeta may play a causative role in the neuronal loss and the inflammatory response associated with AD. Here we show that Abeta-induced toxicity of cultured fetal rat cortical neurons is associated with internucleosomal DNA fragmentation beginning just 6 h after neurons are exposed to Abeta. Additionally, constitutive NF-kappaB activity readily measured in fetal rat cortical neurons decreases in a concentration- and time-dependent fashion following exposure to Abeta, but there is no corresponding decrease in NF-kappaB mRNA or protein (p65). An upregulation of both IkappaB alpha protein and mRNA which occurs in cortical neurons exposed to Abeta may be responsible for retaining NF-kappaB in the cytoplasm accounting for the observed decrease in activated NF-kappaB. The latter is supported by the observation that pretreatment of cortical cultures with an antisense oligonucleotide to IkappaBalpha mRNA is neuroprotective. In contrast to cortical neurons, exposure of rat primary astroglial cultures to Abeta results in a concentration- and time-dependent activation of NF-kappaB with subsequent upregulation of IL-1beta and IL-6. Our data suggest that Abeta-induced neurotoxicity as well as astrocyte activation may be medicated by the NF-kappaB/Rel family of proteins, and thus alterations in NF-kappaB-directed gene expression may contribute to both the neurodegeneration and inflammatory response which occur in AD.

Alzheimer Disease↗
PubMed1998

C/EBPepsilon is a myeloid-specific activator of cytokine, chemokine, and macrophage-colony-stimulating factor receptor genes.

C/EBPepsilon is a member of the CCAAT/enhancer binding protein family of basic region/leucine zipper transcriptional activators. The C/EBPepsilon protein is highly conserved between rodents and humans, and its domain structure is very similar to C/EBPalpha. In mice C/EBPepsilon mRNA is only detected in hematopoietic tissues, including embryonic liver and adult bone marrow and spleen. Within the hematopoietic system, C/EBPepsilon is expressed primarily in myeloid cells, including promyelocytes, myelomonocytes, and their differentiated progeny. To identify potential functions of C/EBPepsilon, cell lines over-expressing the C/EBPepsilon protein were generated in the P388 lymphoblastic cell line. In contrast to the parental cell line, C/EBPepsilon-expressing cell lines displayed lipopolysaccharide-inducible expression of the interleukin-6 and monocyte chemoattractant protein 1 (MCP-1) genes as well as elevated basal expression of the MIP-1alpha and MIP-1beta chemokine genes. In the EML-C1 hematopoietic stem cell line, C/EBPepsilon mRNA levels increased as the cells progressed along the myeloid lineage, just preceding activation of the gene encoding the receptor for macrophage-colony-stimulating factor (M-CSFR). M-CSFR expression was stimulated in C/EBPepsilon-expressing P388 cell lines, when compared with either the parental P388 cells or P388 cell lines expressing either C/EBPalpha or C/EBPbeta. These results suggest that C/EBPepsilon may be an important regulator of differentiation of a subset of myeloid cell types and may also participate in the regulation of cytokine gene expression in mature cells.

Amino Acid Sequence↗
PubMed1998

Superoxide anion from the adventitia of the rat thoracic aorta inactivates nitric oxide.

The purpose of this study was to determine whether superoxide anion is produced endogenously in the rat aortic adventitia and whether sufficient superoxide anion is produced to interfere with the response of the rat aorta to nitric oxide. Relaxation was measured in rings of the rat thoracic aorta, which were oriented so that the adventitial or luminal surface could be preferentially exposed to nitric oxide or sodium nitroprusside. To accomplish this, the rings were mounted (1) with the adventitia facing outward, (2) with the adventitia facing inward after inverting, or (3) with the adventitia facing outward after inverting twice (to control for the inverting procedure). The relaxation to nitric oxide, but not to sodium nitroprusside, was less in rings with the adventitia facing outward compared with those in which it faced inward. In contrast, the response to nitric oxide via either surface was similar when extracellular superoxide anion was scavenged with superoxide dismutase. Incubation of rings with nitro blue tetrazolium (NBT) resulted in blue formazan staining of the adventitia, and lucigenin chemiluminescence was significantly greater when detected from the adventitial compared with the intimal aspect of the artery. The reduction of NBT in intact aortic rings was 30+/-2 pmol x min(-1) x mg(-1) and was significantly decreased by superoxide dismutase to 19+/-2 pmol x min(-1) x mg(-1) and by a synthetic superoxide dismutase mimic, Euk-8, to 11+/-2 pmol x min(-1) x mg(-1). The NADPH oxidase inhibitor, diphenyleneiodonium, decreased NBT reduction to 9+/-1 pmol x min(-1) x mg(-1), whereas inhibitors of xanthine oxidase, mitochondrial oxidases, and nitric oxide synthase were ineffective. Immunohistochemical staining indicated the localization of NADPH oxidase proteins gp91phox, p22phox, p47phox, and p67phox almost exclusively in the adventitia of the rat aorta with no substantial staining in the media. These results indicate that NADPH oxidase located in the adventitia of rat thoracic aorta generates sufficient extracellular superoxide anion to constitute a barrier capable of inactivating nitric oxide. This study suggests that adventitial superoxide anion can play a role in the pathophysiology of the arterial wall.

Acridines↗
PubMed1998

In vitro metabolism of 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naphthyridin-5(7H)- one, a topical antipsoriatic agent. Use of precision-cut rat, dog, monkey and human liver slices, and chemical synthesis of metabolites.

The metabolism of SCH 40120, which is the clinically effective antipsoriatic drug 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzol[b][1,8]naphthyrid in-5(7H)-one, was determined in vitro. Rat, dog, cynomolgus monkey, and human liver slices hydroxylated the aliphatic, cyclohexenyl ring of the drug and conjugated the resulting carbinol. The identified metabolites comprised the corresponding 6-, 7-, and 9-carbinols, the glucuronide of the 6-carbinol, and the 6-ketone derived from the parent drug. Although the three carbinols appeared in the liver isolates of all species studied, the relative amounts of these metabolites varied across species. With a high, non-physiological ratio of substrate to liver, the 6-carbinol and its glucuronide were the major metabolites in human and monkey, whereas the 6-ketone was a minor metabolite in dog. Containing a stereogenic axis and center, the 6-carbinol existed as diastereomeric atropisomers. Its structure was established by 13C and 1H NMR spectroscopy, mass spectrometry, and comparison to an authentic sample.

Animals↗
PubMed1998

Peptide inhibitors of caspase-3-like proteases attenuate 1-methyl-4-phenylpyridinum-induced toxicity of cultured fetal rat mesencephalic dopamine neurons.

Multiple aspartate-specific cysteine proteases have been identified and specific members of this family have been implicated in the apoptotic death of many mammalian cell types. Caspase-3-like proteases seem to play a pivotal role in neuronal apoptosis since mice with germline inactivation of the caspase-3 gene manifest profound alterations in neurogenesis. Moreover, inhibitors of caspase-3-related proteases have been shown to inhibit neuronal apoptosis. Here we extend recent work from our laboratory on the mechanisms mediating the neurotoxic actions of 1-methyl-4-phenylpyridinium using ventral mesencephalon cultures containing dopamine neurons. We demonstrate that low concentrations of 1-methyl-4-phenylpyridinium induce apoptosis in dopamine neurons by morphological and biochemical criteria. Moreover, pretreatment of ventral mesencephalon cultures with the tetrapeptide inhibitors of the caspase-3-like proteases zVAD-FMK or Ac-DEVD-CHO specifically inhibit death of dopamine neurons induced by low concentrations of 1-methyl-4-phenylpyridinium, whereas the caspase-1-like inhibitor Ac-YVAD-CHO was without effect. Our data indicate that exposure of cultured ventral mesencephalon dopamine neurons to low concentrations of 1-methyl-4-phenylpyridinium results in apoptotic death and that caspase-3-like proteases may mediate the neurotoxic apoptotic actions of 1-methyl-4-phenylpyridinium.

1-Methyl-4-phenylpyridinium↗
PubMed1998

Alpha2-macroglobulin attenuates beta-amyloid peptide 1-40 fibril formation and associated neurotoxicity of cultured fetal rat cortical neurons.

Beta-amyloid peptides (A beta) are deposited in an aggregated fibrillar form in both diffuse and senile plaques in the brains of patients with Alzheimer's disease. The neurotoxicity of A beta in cultured neurons is dependent on its aggregation state, but the factors contributing to aggregation and fibril formation are poorly understood. In the present study, we investigated whether alpha2-macroglobulin (alpha2M), a protein present in neuritic plaques and elevated in Alzheimer's disease brain, is a potential regulatory factor for A beta fibril formation. Previous studies in our laboratory have shown that alpha2M is an A beta binding protein. We now report that, in contrast to another plaque-associated protein, alpha1-antichymotrypsin, alpha2M coincubated with A beta significantly reduces aggregation and fibril formation in vitro. Additionally, cultured fetal rat cortical neurons are less vulnerable to the toxic actions of aged A beta following pretreatment with alpha2M. We postulate that alpha2M is able to maintain A beta in a soluble state, preventing fibril formation and associated neurotoxicity.

Alzheimer Disease↗
PubMed1998

Regulation of vascular type 1 angiotensin II receptor in hypertension and sodium loading: role of angiotensin II.

OBJECTIVE: To test the hypotheses that a high sodium intake increases steady state messenger RNA levels of the type 1 angiotensin II receptor in the aorta and mesenteric resistance arteries, and that this increase is mediated by suppression of production of angiotensin II induced by a high sodium intake; and to test the hypotheses that angiotensin II administered at a pressor dose increases steady state messenger RNA levels of the angiotensin II type 1 receptor in the aorta and mesenteric resistance arteries, and that this increase is mediated by activation of angiotensin II type 1 receptors in these vessels. METHODS: In experiment 1, male Wistar rats were divided into four groups and treated for 2 weeks with a (0.5%) normal sodium diet, a normal-sodium diet plus angiotensin II, a high (4%) sodium diet, or a high-sodium plus angiotensin II. We infused 25 ng/kg per min angiotensin II subcutaneously by using osmotic pumps. In experiment 2, male Wistar rats were divided into four groups and treated for 2 weeks with vehicle, 1 mg/kg per day losartan by oral gavage, 250 ng/kg per min angiotensin II by using an osmotic pump), and losartan plus angiotensin II. Angiotensin II type 1 messenger mRNA was measured with the use of quantitative reverse transcriptase-polymerase chain reaction in the presence of an angiotensin II type 1 receptor mutant complementary RNA as internal standard. RESULTS: Results from experiment 1 show that body weight and systolic tail-cuff blood pressures did not differ among our four groups (P > 0.05). Angiotensin II type 1 messenger RNA levels of rats in high-salt diet group were 73% (aorta) and 171% (mesenteric resistance arteries) greater than those of rats in normal-salt diet group (P < 0.05). In contrast, angiotensin II type 1 messenger RNA levels both in aorta and in mesenteric resistance arteries of rats in normal-salt diet plus angiotensin II and high-salt diet plus angiotensin II groups did not differ from those of rats in normal-salt diet group. Results from experiment 2 show that systolic blood pressures in rats treated with angiotensin II and with losartan plus angiotensin II were higher than those in rats administered vehicle (P < 0.05). Mean response of arterial pressure to bolus injection of angiotensin II was suppressed in losartan-treated rats compared with that in rats administered vehicle and in rats treated with losartan plus angiotensin II compared with that in rats treated with angiotensin II (P < 0.05). Angiotensin II type 1 messenger RNA levels were higher by 73% (in aorta) and 63% (in mesenteric resistance arteries) in rats treated with angiotensin II than they were in rats administered vehicle (P < 0.05), but not in both aorta and mesenteric resistance arteries in rats treated with losartan and losartan plus angiotensin II versus rats administered vehicle. CONCLUSION: A high-salt diet increases angiotensin II type 1 messenger RNA levels both in aorta and in mesenteric resistance arteries. This increase is completely suppressed by simultaneous nonpressor infusion of angiotensin II, suggesting that angiotensin II negatively regulates vascular angiotensin II type 1 messenger RNA in normotensive rats. Hypertension induced by pressor infusion of angiotensin II increases angiotensin II type 1 messenger RNA levels both in aorta and in mesenteric resistance arteries. This increase can be prevented by administration of losartan at a nondepressor dose, suggesting that angiotensin II positively regulates vascular angiotensin II type 1 messenger RNA via activation of the angiotensin II type 1 receptor during hypertension.

Angiotensin II↗
PubMed1998

Identification of a novel cortactin SH3 domain-binding protein and its localization to growth cones of cultured neurons.

Cortactin is an actin-binding protein that contains several potential signaling motifs including a Src homology 3 (SH3) domain at the distal C terminus. Translocation of cortactin to specific cortical actin structures and hyperphosphorylation of cortactin on tyrosine have been associated with the cortical cytoskeleton reorganization induced by a variety of cellular stimuli. The function of cortactin in these processes is largely unknown in part due to the lack of information about cellular binding partners for cortactin. Here we report the identification of a novel cortactin-binding protein of approximately 180 kDa by yeast two-hybrid interaction screening. The interaction of cortactin with this 180-kDa protein was confirmed by both in vitro and in vivo methods, and the SH3 domain of cortactin was found to direct this interaction. Since this protein represents the first reported natural ligand for the cortactin SH3 domain, we designated it CortBP1 for cortactin-binding protein 1. CortBP1 contains two recognizable sequence motifs within its C-terminal region, including a consensus sequence for cortactin SH3 domain-binding peptides and a sterile alpha motif. Northern and Western blot analysis indicated that CortBP1 is expressed predominately in brain tissue. Immunofluorescence studies revealed colocalization of CortBP1 with cortactin and cortical actin filaments in lamellipodia and membrane ruffles in fibroblasts expressing CortBP1. Colocalization of endogenous CortBP1 and cortactin was also observed in growth cones of developing hippocampal neurons, implicating CortBP1 and cortactin in cytoskeleton reorganization during neurite outgrowth.

3T3 Cells↗
PubMed1998

Alpha1-adrenergic plus angiotensin receptor blockade reduces atherosclerosis in apolipoprotein E-deficient mice.

-We have used the apolipoprotein E (apoE)-deficient mouse model to determine whether both the angiotensin II type 1 (AT1) and the alpha1-adrenergic receptors influence arteriosclerotic changes in this hyperlipidemic animal model. Mice were treated with antihypertensive drugs beginning at 9 weeks of age, and aortic atherosclerosis was measured after 12 weeks of treatment. Systolic blood pressure in the untreated apoE-deficient mouse averaged 104 mm Hg throughout the treatment period. Prazosin at a dose of 7.5 mg. kg-1. d-1 was ineffective in attenuating atherosclerosis and did not significantly reduce blood pressure. Losartan, at dosages of either 20 or 30 mg. kg-1. d-1, also did not influence atherosclerosis and had only a slight blood pressure-lowering effect. However, combined treatment with both prazosin and losartan markedly reduced atherosclerotic lesion development from an average lesion size per section of 2.6 to 1.5x10(5) microm2 (P<0.001) and significantly reduced blood pressure to 85+/-5 mm Hg. Treatment with NG-nitro-L-arginine methyl ester (40 mg. kg-1. d-1) produced significant elevations of blood pressure (127+/-3.8 mm Hg) but had no effect on the development of atherosclerosis. None of the treatments used affected plasma cholesterol throughout the 12-week period. These studies suggest that the vascular changes associated with atherosclerosis are influenced by a combination of AT1 and alpha1-adrenergic receptor activation.

Adrenergic alpha-Antagonists↗
PubMed1998

Molecular characterization of pyruvate carboxylase deficiency in two consanguineous families.

Pyruvate carboxylase (PC) is a biotinylated mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate. Children with inborn errors of PC metabolism have lactic acidosis, hypoglycemia, and mental retardation. The variable severity of the clinical phenotype is dependent on both genetic and environmental factors. Two consanguineous families with moderate forms of PC deficiency were characterized at the biochemical and molecular levels. In both families, the probands were found to have low PC activity (range, 2-25% of control) in blood lymphocytes and skin fibroblasts associated with either diminished or normal protein levels. In the first case, sequencing of patient-specific PC cDNA demonstrated a T to C substitution at nucleotide 434, which causes a valine to alanine change at amino acid residue 145. Direct sequencing of the parents showed that they are heterozygous for this mutation. In the second family, a brother and sister had mental retardation and episodes of severe lactic/ketoacidosis in early childhood. In these cases, a C to T substitution at nucleotide 1351 results in a cysteine for arginine substitution at amino acid residue 451; the parents were also found to be heterozygous for this mutation. In both families, no other mutations were found, and both substitutions occurred in relatively conserved amino acid residues. These mutations, located in the biotin carboxylase domain, provide a unique opportunity to analyze how natural occurring mutations affect PC function.

Base Sequence↗
PubMed1998

Translocation of cortactin to the cell periphery is mediated by the small GTPase Rac1.

Small GTPases of the Rho family regulate signaling pathways that control actin cytoskeletal structures. In Swiss 3T3 cells, RhoA activation leads to stress fiber and focal adhesion formation, Rac1 to lamellipoda and membrane ruffles, and Cdc42 to microspikes and filopodia. Several downstream molecules mediating these effects have been recently identified. In this report we provide evidence that the intracellular localization of the actin binding protein cortactin, a Src kinase substrate, is regulated by the activation of Rac1. Cortactin redistributes from the cytoplasm into membrane ruffles as a result of growth factor-induced Rac1 activation, and this translocation is blocked by expression of dominant negative Rac1N17. Expression of constitutively active Rac1L61 evoked the translocation of cortactin from cytoplasmic pools into peripheral membrane ruffles. Expression of mutant forms of the serine/threonine kinase PAK1, a downstream effector of Rac1 and Cdc42 recently demonstrated to trigger cortical actin polymerization and membrane ruffling, also led to the translocation of cortactin to the cell cortex, although this was effectively blocked by coexpression of Rac1N17. Collectively these data provide evidence for cortactin as a putative target of Rac1-induced signal transduction events involved in membrane ruffling and lamellipodia formation.

3T3 Cells↗
PubMed1998

Velocity difference measurement with a fiber-optic coupler.

Two single-mode fibers collect light with the same scattered wave vector from two spatially separated regions in a sample. These regions are illuminated by a single coherent laser beam, so that the collected signals interfere when combined by means of a fiber-optic coupler, before they are directed to a photomultiplier tube. The fibers and the coupler are polarization preserving to guarantee a high signal-to-noise ratio. The measured intensity fluctuations are used to determine the velocity difference omega v(L) for spatial separations L in the sample. Specifically, an intensity autocorrelation function is calculated theoretically for rigid body rotation and is tested experimentally. Experimental results span two orders of magnitude in L and agree with theoretical predictions with an error of less than 5%. This new technique will be very useful in the study of turbulent flow and particle settling dynamics.

Fiber Optic Technology↗