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Y Du

Publications and source records attributed to Y Du.

At least 145 records · Page 8Linked to original sources
PubMed1997

Regulation of type 1 angiotensin II receptor in adrenal gland: role of alpha1-adrenoreceptor.

We have previously shown that sodium restriction upregulates the genes encoding angiotensin II receptor (AT1) subtypes, AT1A and AT1B, in the adrenal gland and that this upregulation is mediated by activation of the AT1 receptor. There are multiple interactions between the renin-angiotensin and the adrenergic nervous systems; thus, we conducted the present experiment to investigate whether low sodium-induced upregulation of adrenal AT1A and AT1B is modulated by the alpha1-adrenoreceptor. Seven-week-old male Wistar rats were divided into four groups and given normal sodium diet (0.5%, NS), NS+prazosin (3.5 microg x kg(-1) x min(-1) by osmotic pump), low sodium diet (0.07%, LS), or LS+prazosin. Body weight and mean arterial pressure were not modified over the 2 weeks of treatment (P>.05). Pressor responses to bolus injection of the alpha1-agonist phenylephrine were inhibited in both prazosin groups, compared with NS and LS rats (P<.05). Adrenal AT1A mRNA, determined by Northern blot analysis, was increased in LS (P<.05) but not in NS+prazosin (P>.05), compared with NS. Prazosin enhanced the LS-induced increase of AT1A mRNA (P<.05). Adrenal AT1B mRNA was increased in both LS and NS+prasozin rats, compared with NS rats (P<.05). Prazosin also enhanced the LS-induced increase in AT1B mRNA (P<.05). Therefore, blockade of alpha1-adrenoreceptor results in an enhancement of LS-induced upregulation of adrenal mRNA for AT1A and AT1B. These data suggest that the sympathetic nervous system exerts an inhibitory action, via activation of the alpha1-adrenoreceptor, on AT1A and AT1B gene expression in the adrenal gland during sodium depletion.

Adrenal Glands↗
PubMed1997

Regulation of angiotensin type 1 receptor and its gene expression: role in renal growth.

Low sodium intake has been demonstrated to upregulate the gene expression of the predominant renal type 1 angiotensin II (Ang II) receptor (AT1), the AT1A subtype. The study presented here tests the hypothesis that the upregulation of renal AT1 mRNA induced by sodium depletion occurs conjointly with an elevation of the AT1 receptor that modulates renal growth. Seven-week-old male Wistar rats were divided into four groups and treated for 2 wk with normal sodium diet, normal sodium diet plus 3 mg/kg/day losartan, low sodium diet, or low sodium diet plus losartan. Body weight and MAP were not significantly different among the four groups. Plasma renin activity was significantly elevated by losartan treatment, low salt intake, or a combination of the two, compared with the plasma renin activity of the controls. Northern blot analysis indicated that renal AT1 mRNA levels were significantly increased-183% by losartan, 212% by low salt intake, and 227% by the combination of the two-compared with their levels in controls. Radioligand binding assays revealed that AT1 receptors were significantly increased by low salt intake but were significantly decreased by losartan treatment. Renal AT1 receptor binding in the rats subjected to sodium depletion plus losartan did not differ from that in control rats. Kidney weight, kidney weight/body weight ratio, and renal DNA and protein content were not altered by sodium depletion but were significantly lowered by losartan treatment with both normal and low sodium intake, compared with those of controls. The protein/DNA ratio was not significantly different among the four groups. Blockade of renal AT1 receptors with losartan was found to retard normal renal growth, indicating that Ang II is required for normal renal development. Low sodium intake was found to increase mRNA and expression of the renal AT1 receptor but to have no effect on renal growth, suggesting that an increase in renal mass above a normal level requires the activation of multiple factors. Blockade of the AT1 receptor by losartan was found to upregulate AT1 mRNA but to down-regulate the AT1 receptor, suggesting that AT1 receptor-mediated intracellular events are necessary to sustain functional AT1 receptor expression in the kidney.

Animals↗
PubMed1997

alpha2-Macroglobulin as a beta-amyloid peptide-binding plasma protein.

The beta-amyloid peptide (A beta) is a normal proteolytic processing product of the amyloid precursor protein, which is constitutively expressed by many, if not most, cells. For reasons that are still unclear, A beta is deposited in an aggregated fibrillar form in both diffuse and senile plaques in the brains of patients with Alzheimer's disease (AD). The factor(s) responsible for the clearance of soluble A beta from biological fluids or tissues are poorly understood. We now report that human alpha2-macroglobulin (alpha2M), a major circulating endoproteinase inhibitor, which has recently been shown to be present in senile plaques in AD, binds 125I-A beta(1-42) with high affinity (apparent dissociation constant of 3.8 x 10(-10) M). Approximately 1 mol of A beta is bound per mole of alpha2M. Both native and methylamine-activated alpha2M bind 125I-A beta(1-42). The binding of 125I-A beta(1-42) to alpha2M is enhanced by micromolar concentrations of Zn2+ (but not Ca2+) and is inhibited by noniodinated A beta(1-42) and A beta(1-40) but not by the reverse peptide A beta(40-1) or the cytokines interleukin 1beta or interleukin 2. alpha1-Antichymotrypsin, another plaque-associated protein, inhibits both the binding of 125I-A beta(1-42) to alpha2M as well as the degradation of 125I-A beta(1-42) by proteinase-activated alpha2M. Moreover, the binding of 125I-A beta(1-42) to alpha2M protects the peptide from proteolysis by exogenous trypsin. These data suggest that alpha2M may function as a carrier protein for A beta and could serve to either facilitate or impede clearance of A beta from tissues such as the brain.

Amyloid beta-Peptides↗
PubMed1996

Genetic maps of polymorphic DNA loci on rat chromosome 1.

Genetic linkage maps of loci defined by polymorphic DNA markers on rat chromosome 1 were constructed by genotyping F2 progeny of F344/N x LEW/N, BN/SsN x LEW/N, and DA/Bkl x F344/Hsd inbred rat strains. In total, 43 markers were mapped, of which 3 were restriction fragment length polymorphisms and the others were simple sequence length polymorphisms. Nineteen of these markers were associated with genes. Six markers for five genes, gamma-aminobutyric acid receptor beta3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor beta1 (Adrb1), carcinoembryonic antigen gene family member 1 (Cgm1), and lipogenic protein S14 (Lpgp), and 20 anonymous loci were not previously reported. Thirteen gene loci (Myl2, Aldoa, Tnt, Igf2, Prkcg, Cgm4, Calm3, Cgm3, Psbp1, Sa, Hbb, Ins1, and Tcp1) were previously mapped. Comparative mapping analysis indicated that a large portion of rat chromosome 1 is homologous to mouse chromosome 7, although the homologs of two rat genes are located on mouse chromosomes 17 and 19. Homologs of the rat chromosome 1 genes that we mapped are located on human chromosomes 6, 10, 11, 12, 15, 16, and 19.

Animals↗
PubMed1996

Assessment of chromatographic peak purity by means of artificial neural networks.

An improved chemometric approach is proposed for assessing chromatographic peak purity by means of artificial neural networks. A non-linear transformation function with a back-propagation algorithm was used to describe and predict the chromatographic data. The Mann-Whitney U-test was used for the concluding the purity of the chromatographic peak. Simulation data and practical analytical data for both pure and mixture samples were analysed with satisfactory results. A prior knowledge of the impurity and the related compound is unnecessary when a slight difference between their chromatogram and spectrum exists. The performance on simulated data sets by this approach was compared with the results from principal component analysis.

Algorithms↗
PubMed1996

Linkage maps of rat chromosomes 15, 16, 17, 19, and X.

Linkage maps of rat chromosomes 15, 16, 17, 19, and X were constructed by multipoint genetic linkage analysis of 22 polymorphic markers in 40 F2 progeny of Fischer (F344/N) and Lewis (LEW/N) inbred rat strains. These markers are associated with eight genes (angiotensin receptor A, M3 muscarinic acetylcholine receptor, heme oxygenase, endothelin receptor A, haptoglobin, tyrosine aminotransferase, phosphoribosylpyrophosphate synthetase subunit II, and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase) and 14 anonymous loci. Linkage analysis placed the markers into five linkage groups covering 11.7,7.9,11.6,42.5, and 5.1cM. These linkage groups were assigned to rat chromosomes 15, 16, 17, 19, and X, respectively, either by mouse x rat somatic cell hybrid analysis or based on previously identified locations of severalloci. In polymorphism analysis, these markers exhibited two to nine different alleles in 16 inbred rat strains.

Alleles↗
PubMed1996

Pancreatic microcirculation in the monkey with special reference to the blood drainage system of Langerhans islets: light and scanning electron microscopic study.

The microcirculation of the pancreas in 20 monkeys (Macaca mulatta) was further studied by scanning electron microscopy (SEM) of vascular corrosion casts and light microscopy (LM) of Chinese ink-injected/cleared tissues. The results revealed that 91% of islets observed received arterial blood from the terminal branches of the intralobular arteries--the afferent arterioles, and 9% received no arterial blood, being entirely supplied by the efferent vessels of the intermediate or large islets. Some islets received blood from the translobular afferent arterioles of the adjacent lobule. Two patterns of islet drainage channels with different features in the monkey were demonstrated in our study. These patterns might be termed as continuous or convergent portal vessels. All islets possessed continuous portal vessels, 7-8 microns in diameter, which ran a short distance (approximately 100 microns) and then drained into the peri-islet acinar region, forming a typical continuous insulo-acinar portal system. About 21% of the islets possessed one or two convergent portal vessels, occasionally more. This was first observed in the monkey. These vessels were relatively long and/or thick and drained into different regions: (1) the acinar region far from the islet in the lobule, forming a convergent insulo-acinar portal system, (2) crossed the interlobular septum into an adjacent lobule where sometimes no islet existed and then drained into the exocrine acinar region, forming a translobar convergent insulo-acinar portal system, (3) drained into an adjacent small islet through the insulo-insular drainage vessels--one part of the drainage system of the islets. Translobular vascular anastomoses observed between the microcirculation of pancreatic lobules in the monkey formed a new arrangement of pancreatic microcirculation-translobular pancreatic microcirculation. The functional and clinical significance of the pancreatic portal circulation and translobular circulation is discussed in this report.

Animals↗
PubMed1996

Localization of the gene responsible for the op (osteopetrotic) defect in rats on chromosome 10.

Osteopetrosis, a skeletal disorder of inadequate bone resorption with an abnormal increase in skeletal mass, results from a variety of independent single gene mutations that affect osteoclast differentiation and/or function. The osteopetrotic defect, op, is one of four spontaneous, nonallelic mutations in rats that result in osteopetrosis. In intercross progeny of (BN/SsN x LEW/SsN. +/op) F1 carriers, we mapped this locus by linkage analysis with microsatellite markers to rat chromosome 10. The linkage group contained, as well as op, 15 anonymous DNA loci and 9 DNA loci associated with genes (interleukin-3, myosin heavy chain [skeletal, embryonic], asialoglycoprotein receptor [hepatic lectin]-1, vesicle-associated membrane protein [synaptobrevin-2], sex hormone binding globulin, aldolase C, nitric oxide synthase [inducible], erythroblastic leukemia avian viral oncogene homolog-2, and proline-rich protein). The markers for these loci include nine not previously reported. The op locus mapped to the end of the chromosome 10 linkage group, within 1 cM of the anonymous DNA locus, D10Mit6. Based on its location, the op gene is likely to be distinct from seven described mutations in mice as well as three other mutations in rats. These results may permit a positional cloning strategy to be undertaken to identify the gene and mutation underlying the op defect.

Animals↗
PubMed1996

Single molecule detection of RNA reporter probes by amplification with Q beta replicase.

The addition of target-specific probe sequences within MDV RNA, an otherwise efficient template for Q beta replicase, generally resulted in RNA molecules with inferior replication properties, including reduced replication rates and poor sensitivities. We have discovered that the replication characteristics of MDV RNA molecules with internally placed probe sequences are dramatically affected by short RNA sequences (spacer elements) at the 5' and 3' ends of the probe sequence. For a given probe sequence, the sequences of the flanking spacer elements effected replication sensitivity by six orders of magnitude and replication rate by three fold. By taking advantage of spacer elements, internal MDV probes were developed that permitted the reproducible, real time, fluorescence detection of a single RNA molecule in less than 25 min through amplification with Q beta replicase. RNA structural analysis of such probes suggested that the spacer elements functioned by allowing the RNA to fold in a way which substantially maintained the tertiary structure of the MDV domain. MDV reporter probes with suitable replication properties were obtained from libraries of RNA molecules in which the probe sequence was flanked by many different spacer elements (generated by random nucleotide synthesis). We demonstrated that this is a general method for developing RNA reporter molecules which are rapidly and reproducibly amplified by Q beta replicase, even from a single molecule.

Base Sequence↗
PubMed1996

Solid-state NMR investigation of acid sites in dealuminated HZSM-5 zeolite.

The acid sites and the hydration behaviors of dealuminated HZSM-5 zeolites (calcined at 550, 600, 650, and 700 degrees C) were characterized by high-resolution 1H MAS, 1H{27A1} spin-echo double resonance in combination with 27A1 MAS NMR. Apart from the usually observed peaks for dealuminated zeolite HZSM-5, a narrow plus a broad peak simultaneously appears at ca. 6.9 ppm in the 1H spectra and they exhibit different decay behavior in the 1H [27A1] double-resonance experiments. The existence of the former signal indicates that Lewis acid sites may'be formed in the zeolites after calcination. By means of the spin echo double resonance technique, we observed for the first time a previously unexpected narrow signal at 5.2 ppm, which resonates on the downfield side of Bronsted acid signal (4.3 ppm) and cannot be resolved in the 1H MAS spectra. This new signal is probably due to another kind of Bronsted acid site, locating in the small cages bounded by four- and five-membered rings. Three narrow peaks at 50 ppm, 30 ppm, and 0 ppm are superimposed on a very broad signal in the 27A1 MAS NMR spectra of dried HZSM-5. The intensity of the line at 50 ppm is significantly reduced compared with that of the rehydrated sample. 27A1 MAS NMR suggests that most part of the four-coordinated framework A1 turns into a intermediate case between four- and three-coordinated A1 after the dehydration and this process is reversible upon dehydration/rehydration. While some framework A1 atoms are transformed into three-coordinated A1 species and Lewis acid sites are, thus, generated in the dealuminated zeolites. For the signal at 30 ppm, the hydration leads to a dispersion in the chemical shift or the quadrupole interaction, which broadens its linewidth in hydrated samples.

Magnetic Resonance Spectroscopy↗
PubMed1996

A genome scan localizes five non-MHC loci controlling collagen-induced arthritis in rats.

Identification of specific genetic loci that contribute to susceptibility to rheumatoid arthritis (RA) in humans has been hampered by several factors, including: i) multiple interacting genetic loci contributing to susceptibility; ii) complex interactions of environmental and genetic factors; iii) genetic heterogeneity; and iv) low penetrance. We have, therefore, mapped quantitative trait loci (QTLs) that control inflammatory arthritis susceptibility and/or severity in progeny of two inbred rat strains with significantly different susceptibilities to collagen-induced arthritis (CIA), an animal model for RA. Not surprisingly, we identified a major susceptibility factor, Cia1, on chromosome 20 in the vicinity of the rat major histocompatibility complex (MHC). However, by limiting the analysis to animals with arthritis-susceptible MHC genotypes and using genome-wide QTL analytic techniques, we also found four non-MHC QTLs-Cia2, 3, 4 and 5-on chromosomes 1, 4, 7 and 10, that contributed to disease severity. In addition, a QTL on chromosome 8 was suggestive for linkage. Characterization of the genes underlying these QTLs will facilitate the identification of key biochemical pathways regulating experimental autoimmune arthritis in rats and may provide insights into RA and other human autoimmune diseases. These genes may also represent novel targets for therapy.

Animals↗
PubMed1996

Molecular cloning, expression, and chromosomal localization of a human brain-specific Na(+)-dependent inorganic phosphate cotransporter.

We describe the molecular cloning of a cDNA encoding a human brain Na(+)-dependent inorganic phosphate (P(i)) cotransporter (hBNPI). The nucleotide and deduced amino acid sequences of hBNPI reveal a protein of 560 amino acids with six to eight putative transmembrane segments. hBNPI shares a high degree of homology with other Na(+)-dependent inorganic P(i) cotransporters, including those found in rat brain and human and rabbit kidney. Expression of hBNPI in COS-1 cells results in Na(+)-dependent P(i) uptake. Northern blot analysis demonstrates that hBNPI mRNA is expressed predominantly in brain and most abundantly in neuron-enriched regions such as the amygdala and hippocampus. Moderate levels of expression are also observed in glia-enriched areas such as the corpus callosum, and low levels are observed in the substantia nigra, subthalamic nuclei, and thalamus. In situ hybridization histochemistry reveals relatively high levels of hBNPI mRNA in pyramidal neurons of the cerebral cortex and hippocampus and in granule neurons of dentate gyrus. The level of hBNPI mRNA is quite low in fetal compared with adult human brain, suggesting developmental regulation of hBNPI gene expression. Southern analyses of nine eukaryotic genomic DNAs probed under stringent conditions with hBNPI cDNA revealed that the hBNPI gene is highly conserved during vertebrate evolution and that each gene is most likely present as a single copy. Using fluorescent in situ hybridization, we localized hBNPI to the long arm of chromosome 19 (19q13) in close proximity to the late-onset familial Alzheimer's disease locus.

Animals↗
PubMed1996

Regulation of type 1 angiotensin II receptor and its subtype gene expression in kidney by sodium loading and angiotensin II infusion.

OBJECTIVE: To test the hypothesis that a high salt intake decreases gene expression of both type 1 angiotensin receptor subtypes 1A and 1B (AT1A and AT1B) and diminishes AT1 receptor density in the kidney through an angiotensin II (Ang II)-independent mechanism. METHODS: Wistar rats were divided into four groups and fed a normal-sodium diet (0.5%, NSD), NSD + 25 ng/kg per min Ang II infusion, a high-sodium diet (4%, HSD), or HSD + Ang II infusion for 2 weeks. Quantitative reverse transcriptase-polymerase chain reaction was used for analysis of changes in renal AT1A and AT1B messenger RNA (mRNA) levels. Radioligand binding assays were used for measurement of Ang II receptor density. RESULTS: Body weight and mean arterial pressure did not differ among the four groups. Renal AT1A and AT1B mRNA levels were decreased significantly in NSD + Ang II and HSD + Ang II groups compared with those in the NSD group. Renal AT1B mRNA was also decreased significantly in HSD versus NSD. The renal AT1 receptor density was decreased significantly in NSD + Ang II and HSD + Ang II, but was not changed in HSD compared with NSD. CONCLUSION: A high salt intake downregulates the AT1B mRNA expression but does not change the AT1A mRNA expression and AT1 receptor density in the kidney, suggesting that differential regulation occurs in the kidney. Infusion of a nonpressor dose of Ang II, either alone or in conjunction with a high salt intake, downregulates the AT1 receptor and its subtype gene expression in the kidney, suggesting that Ang II regulates these responses through a negative feedback mechanism.

Angiotensin II↗
PubMed1996

Regulation of ANG II-receptor subtype and its gene expression in adrenal gland.

We have previously demonstrated that two isoforms (AT1A and AT1B) of the angiotensin II (ANG II) type 1 (AT1) receptor exist in the rat kidney and are differentially regulated by a low-sodium diet. The present experiment was designed to test the hypothesis that sodium deficiency upregulates AT1A and AT1B gene expression in the adrenal gland by activating the AT1 receptor. Wistar rats (7 wk old) were divided into four groups (n = 10 each) and fed normal sodium (0.5%; NS), NS plus 3 mg.kg-1.day-1 losartan (DUP-753; i.e., DUP), low sodium (0.07%; LS), and LS plus DUP. After 2 wks, body weight and mean arterial pressure were not different (P > 0.05). Northern blot analysis showed that the ratio of AT1A: glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA in the adrenal gland was increased (P < 0.001) by 172% in LS but was unchanged in NS + DUP and LS + DUP vs. NS. The ratio of adrenal AT1B:GAPDH mRNA was increased (P < 0.001) by 245% in LS and unchanged in NS + DUP and LS + DUP vs. NS. Radioligand binding indicated that AT1 receptors (fmol/mg protein) in the adrenal gland were increased in LS (141 +/- 17; P < 0.001) vs. NS (54 +/- 3), NS + DUP (43 +/- 5), and LS + DUP (56 +/- 6). We conclude that sodium deficiency increases both AT1A and AT1B gene expression and elevates the AT1 receptor density in the adrenal gland. Blockade of the binding of ANG II to the AT1 receptor by losartan prevents the increases in AT1A and AT1B mRNA expression and the AT1 receptor density induced by sodium depletion, suggesting that these changes in the adrenal gland are mediated by activation of the AT1 receptor. These results will provide a basis for future experiments to further elucidate transcriptional regulation or functional activity of each of the receptor subtypes.

Adrenal Glands↗