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Y Fu

Publications and source records attributed to Y Fu.

At least 127 records · Page 7Linked to original sources
PubMed1999

A new potent antigen from Echinococcus granulosus associated with muscles and tegument.

An immunoscreening of a cDNA library derived from the adult stage of the parasitic platyhelminth Echinococcus granulosus has been carried out with sera from infected dogs. The EgA31 clone encodes a fibrous protein which shares some sequence elements with paramyosins. The corresponding gene is present as a single copy in the genome. As revealed by an antibody obtained against a fusion protein produced in bacteria, the polypeptide has a molecular weight of 66 kDa. This polypeptide is present at all developmental stages studied and is a potent antigen during an infection by the adult stage in the dog and during cyst growth in human patients. By immunohistology, it was shown that it is present in the tegument and subtegumental parenchyma of the adult with a main location in the region of the suckers where it rapidly accumulates at the time of the head evagination. It is also present in the germinal layer of the cyst and on the protoscolex.

Amino Acid Sequence↗
PubMed1999

Notochord-dependent expression of MFH1 and PAX1 cooperates to maintain the proliferation of sclerotome cells during the vertebral column development.

During axial skeleton development, the notochord is essential for the induction of the sclerotome and for the subsequent differentiation of cartilage forming the vertebral bodies and intervertebral discs. These functions are mainly mediated by the diffusible signaling molecule Sonic hedgehog. The products of the paired-box-containing Pax1 and the mesenchyme forkhead-1 (Mfh1) genes are expressed in the developing sclerotome and are essential for the normal development of the vertebral column. Here, we demonstrate that Mfh1 like Pax1 expression is dependent on Sonic hedgehog signals from the notochord, and Mfh1 and Pax1 act synergistically to generate the vertebral column. In Mfh1/Pax1 double mutants, dorsomedial structures of the vertebrae are missing, resulting in extreme spina bifida accompanied by subcutaneous myelomeningocoele, and the vertebral bodies and intervertebral discs are missing. The morphological defects in Mfh1/Pax1 double mutants strongly correlate with the reduction of the mitotic rate of sclerotome cells. Thus, both the Mfh1 and the Pax1 gene products cooperate to mediate Sonic hedgehog-dependent proliferation of sclerotome cells.

Animals↗
PubMed1999

Inhibition of nicotine-induced hippocampal norepinephrine release in rats by alpha-conotoxins MII and AuIB microinjected into the locus coeruleus.

Hippocampal norepinephrine (NE) is secreted by neurons projecting from the locus coeruleus (LC) to the hippocampus; LC nicotinic receptors (NAchRs) are involved in the effects of systemic nicotine on this pathway. To clarify the NAchR subtypes, NAchR antagonists, termed alpha-conotoxins, were microinjected into the LC before nicotine; MII and AuIB were used to assess the potential involvement of alpha3beta2 and alpha3beta4 subunit-containing NAchRs, respectively. Nicotine dose-dependently stimulated hippocampal NE release (P < 0.01). MII (>0.25 pmol) reduced the NE response to nicotine (67% decrease; P < 0.05), as did AuIB (44% reduction by 25 pmol; P < 0.05). Administered together, however, MII and AuIB were no more effective than MII. Thus, MII and AuIB are capable of interacting with NAchR subtypes other than those previously defined as alpha3beta2 and alpha3beta4, respectively. NAchRs containing both beta2 and beta4-subunits may be involved.

Animals↗
PubMed1999

TOM1 genes map to human chromosome 22q13.1 and mouse chromosome 8C1 and encode proteins similar to the endosomal proteins HGS and STAM.

The avian tom1 (target of myb 1) gene has been previously characterized from v-myb-transformed cells. We report here cloning of the human and mouse tom1 orthologs. Both genes are expressed ubiquitously, with the highest levels in skeletal muscle, brain, and intestines, as assessed by Northern blot and mRNA in situ hybridization. The N-terminal domain of the TOM1 protein shares similarity with HGS (hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (signal-transducing adaptor molecule), which are associated with vesicular trafficking at the endosome. A putative coiled-coil domain was also detected in the central part of the TOM1 protein. This domain structure suggests that TOM1 is another member of a family of genes implicated in the trafficking regulation of growth-factor-receptor complexes that are destined for degradation in the lysosome. We also show that a human paralog of TOM1 (TOM1-like gene 1) exists. Furthermore, we provide a transcription map over a 190-kb contig of the TOM1 region. This map includes its distal neighbors HMOX1 and MCM5 and two proximal novel genes, one of which is a HMG-box-containing gene (HMG2L1), and the other of unknown function. Using a genomic PAC clone, we demonstrate that the mouse Tom1 and Hmox1 genes are part of an as yet undescribed syntenic group between mouse chromosome 8C1 and human chromosome 22q13.1.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Heat stability of the potato tuber ADP-glucose pyrophosphorylase: role of Cys residue 12 in the small subunit.

Most of the ADP-glucose pyrophosphorylases from different sources are stable to a heat treatment. We found that in the potato (Solanum tuberosum L.) tuber enzyme, the intermolecular disulfide bridge located between Cys12 of the small subunits is responsible for the stability at 60 degrees C. When this unique disulfide bond is cleaved the enzyme is stable up to 40 degrees C. Mutation of Cys12 in the small subunit into either Ala or Ser yielded enzymes with stability similar to the reduced form of the wild type. Concurrently, the enzyme with a truncated small subunit on the N-terminal was stable only up to 40 degrees C. Thus, the N-terminal is important for the stability of the enzyme because of the presence of a disulfide bond.

Adenosine Diphosphate Glucose↗
PubMed1999

Discovery of a regulatory motif that controls the exposure of specific upstream cyclin-dependent kinase sites that determine both conformation and growth suppressing activity of pRb.

The conformation and activity of pRb, the product of the retinoblastoma susceptibility gene, is dependent on the phosphorylation status of one or more of its 16 potential cyclin-dependent kinase (cdk) sites. However, it is not clear whether the phosphorylation status of one or more of these sites contributes to the determination of the various conformations and activity of pRb. Moreover, whether and how the conformation of pRb may regulate the phosphorylation of the cdk sites is also unclear. In the process of analyzing the function and regulation of pRb, we uncovered the existence of an unusual structural motif, m89 (amino acids 880-900), the mutation of which confers upon pRb a hypophosphorylated conformation. Mutation of this structural domain activates, rather than inactivates, the growth suppressor function of pRb. In order to understand the effect of the mutation of m89 on the phosphorylation of cdk sites, we identified all the cdk sites (Thr-356, Ser-807/Ser-811, and Thr821) the phosphorylation of which drastically modify the conformation of pRb. Mutation of each of these four sites alone or in combinations results in the different conformations of pRb, the migration pattern of which, on SDS-polyacrylamide gel electrophoresis, resembles various in vivo hypophosphorylated forms. Each of these hypophosphorylated forms of pRb has enhanced growth suppressing activity relative to the wild type. Our data revealed that the m89 structural motif controls the exposure of the cdk sites Ser-807/Ser-811 in vitro and in vivo. Moreover, the m89 mutant has enhanced growth suppressing activity, similar to a mutant with alanine substitutions at Ser-807/Ser-811. Our recent finding, that the m89 region is part of a structural domain, p5, conserved antigenically and functionally between pRb and p53, suggests that the evolutionarily conserved p5 domain may play a role in the coordinated regulation of the activity of these two tumor suppressors, under certain growth conditions.

Amino Acid Sequence↗
PubMed1999

Determination of trace elements in tissue of human uterine cancer by instrumental neutron activation analysis.

In this article, the low-temperature freeze-drying pretreated technique and instrumental neutron activation analysis were used to determine 29 trace elements in samples of human uterine cancer tissue. The content of these trace elements in uterine cancer tissue was compared with that in cervicitis tissue and in healthy tissue, respectively. Preliminary results indicated that significant differences in contents of Au, I, and Se were observed in these tissues.

Female↗
PubMed1999

Genetic susceptibility to pre-eclampsia and chromosome 7q36.

Pre-eclampsia is the most common serious medical disorder of human pregnancy. The human endothelial cell nitric oxide synthase (eNOS) gene is a candidate for pre-eclampsia/eclampsia (PE/E) susceptibility. A linkage study was performed on Australian PE/E families using 25 microsatellite markers from chromosome 7, one of which (eNOS-CA) resides within the eNOS gene. No significant linkage was found for the eNOS-CA marker using either parametric or non-parametric analysis. However, D7S 1805 from the eNOS gene region on 7q36, gave a suggestion of linkage using parametric analysis (maximum LOD score =2.143 at theta=0.14) and non-parametric APM analysis (T1/sqrt(p)=3.53; P=0.002). Further, an association study was performed on unrelated PE/E cases and controls from both Chinese and Australian populations to test for a relationship between the eNOS gene and PE/E. No association was found between the eNOS-CA marker and PE/E in either population. However, there was a significant difference in the allelic distribution of eNOS-CA between the two ethnic groups. The linkage results support the possibility that a susceptibility locus for pre-eclampsia resides in the 7q36 region, however, there is no definitive evidence to support the notion that the eNOS gene itself is responsible for susceptibility to pre-eclampsia.

Asian People↗
PubMed1999

Inhibitory effect of methylene blue-induced photooxidation on intimal thickening of vein graft.

BACKGROUND: We have previously speculated that methylene blue-induced photooxidation of adventitial surface for 5 minutes can completely inhibit the intimal and medial growth of surgically prepared saphenous vein in vitro. In this study, inhibitory effect of methylene blue-induced photooxidation on intimal thickening of vein graft in vivo was investigated. METHODS: Jugular vein grafts were photooxidized in 0.01% methylene blue solution for 5 minutes, and interposed into arterial circulation for 4 weeks in rabbits. Vein grafts were studied by morphometry and immunohistochemistry. RESULTS: The intimal thickening of photooxidized vein grafts were suppressed significantly compared with those in the nonphotooxidized group. Proliferated cell nuclear antigen (PCNA) index (total PCNA-positive cells/total cell count x 100%) of vein graft was significantly higher in the nonphotooxidized group than those in the photooxidized group. CONCLUSIONS: Methylene blue-induced photooxidation is effective in the inhibition of intimal thickening of vein graft interposed in the arterial circulation for 4 weeks in vivo.

Animals↗
PubMed1999

Association of K-ras mutations with p16 methylation in human colon cancer.

BACKGROUND & AIMS: K-ras mutations are early genetic changes in colon cancer. p16, a tumor-suppressor gene, is inactivated in neoplasms by mutation, deletion, or methylation. The aims of this study were to determine p16 methylation status and its possible association with K-ras mutations in human colon cancer. METHODS: DNA isolated from 8 colon cancer cell lines and 41 microdissected human colon tissue samples was analyzed. p16 methylation status was determined using two analytical methods. The level of p16 expression was determined by reverse-transcription polymerase chain reaction and Northern blot. K-ras mutations were determined by DNA sequence analysis. The DNA methyltransferase activity was determined by microassay. Parental and K-ras-transformed IEC-18 cells were used to determine the potential association between K-ras mutations and p16 methylation. RESULTS: Methylated p16 was found in 100% of colon cancer cell lines, 55% of colon cancers, 54% of adenomas, and 25% of transitional mucosa but not in normal colonic epithelium. Forty-five percent of cancers and 38% of adenomas showed both K-ras mutations and p16 methylation. Of 11 cancers and adenomas with K-ras mutation, 10 specimens showed methylated p16. In contrast, of 13 adenomas and cancers with wild-type K-ras, only 3 specimens showed methylated p16 (P = 0.001). Stable transformation of IEC-18 cells with K-ras increased the DNA methyltransferase activity, methylated the p16 gene, and suppressed the expression of p16. Treatment with a DNA methylation inhibitor (azadeoxycytidine) resulted in reexpression of p16 in K-ras-transformed IEC-18 cells, suggesting that the expression of p16 was suppressed by DNA methylation. CONCLUSIONS: p16 methylation occurs frequently in human colonic adenomas and cancers and is closely associated with K-ras mutations.

Azacitidine↗
PubMed1999

Knockout of cellular glutathione peroxidase gene renders mice susceptible to diquat-induced oxidative stress.

Two experiments were conducted to determine the protection and the underlying mechanisms of cellular glutathione peroxidase (GPX1) against lethal, acute oxidative stress induced by an intraperitoneal injection of 24 mg diquat/kg body weight. In experiment 1, mortality and survival times were compared among selenium (Se)-adequate or deficient GPX1 knockout mice [GPX1(-/-)] and wild-type mice (WT). In experiment 2, mice from these four groups were euthanized at 0, 1, 2, and 3 h after the injection of diquat to elucidate the time course of oxidative events. The stress produced 100% mortality in all of the groups except for the Se-adequate WT, which were euthanized on day 7 for analysis. The Se-deficient WT and the Se-adequate GPX1(-/-) had similar survival times (4.1 and 3.9 h), which were longer (p < .05) than that of the Se-deficient GPX1(-/-) (2.4 h). However, these three GPX1-deficient groups had higher levels (p < .05) of hepatic F2-isoprostanes and carbonyl contents and/or plasma alanine aminotransferase activities than those of the Se-adequate WT. The diquat-induced formations of hepatic F2-isoprostanes in these animals peaked at 1 h and preceded the rise of plasma alanine aminotransferase in the Se-adequate GPX1(-/-). Responses of hepatic superoxide dismutase activities to the diquat treatment were affected by the GPX1 level. In conclusion, GPX1 is the major selenoprotein to protect mice against the lethal oxidative stress induced by diquat.

Alanine Transaminase↗
PubMed1999

Cellular glutathione peroxidase protects mice against lethal oxidative stress induced by various doses of diquat.

This study was to determine if cellular glutathione peroxidase (GPX1) protects against acute oxidative stress induced by diquat. Lethality and hepatic biochemical indicators in GPX1 knockout mice [GPX1(-/-)] were compared with those of wild-type mice (WT) after an intraperitoneal injection of diquat at 6, 12, 24, or 48 mg/kg of body weight. Although the WT survived all the doses, the GPX1(-/-) survived only 6 mg diquat/kg and were killed by 12, 24, and 48 mg diquat/kg at 52, 4.4 and 3.9 hr, respectively. Compared with those of surviving mice that were sacrificed on Day 7, the dead GPX1(-/-) had diquat dose-dependent increases (P < 0.05) in plasma alanine aminotransferase (ALT) activities. The GPX1(-/-) also had higher (P < 0.05) liver carbonyl contents than those of the WT, but the differences were irrespective of diquat doses. Whereas hepatic total GPX and phospholipid hydroperoxide glutathione peroxidase activities or hepatic GPX1 protein was not significantly affected by the diquat treatment, liver thioredoxin reductase and catalase activities were lower (P < 0.05) in the GPX1(-/-) injected with 12 mg diquat/kg than those of other groups. In conclusion, normal GPX1 expression is necessary to protect mice against the lethality, hepatic protein oxidation, and elevation of plasma ALT activity induced by 12-48 mg diquat/kg.

Animals↗
PubMed1999

Dietary intrinsic phytate protects colon from lipid peroxidation in pigs with a moderately high dietary iron intake.

High iron consumption has been proposed to relate to an increase in the risk of colon cancer, whereas high levels of supplemental sodium phytate effectively reduce iron-induced oxidative injury and reverse iron-dependent augmentation of colorectal tumorigenesis. However, the protective role of intrinsic dietary phytate has not been determined. In this study, we examined the impact of removing phytate present in a corn-soy diet by supplemental microbial phytase on susceptibility of pigs to the oxidative stress caused by a moderately high dietary iron intake. Thirty-two weanling pigs were fed the corn-soy diets containing two levels of iron (as ferrous sulfate, 80 or 750 mg/kg diet) and microbial phytase (as Natuphos, BASF, Mt. Olive, NJ, 0 or 1200 units/kg). Pigs fed the phytase-supplemented diets did not receive any inorganic phosphorus to ensure adequate degradation of phytate. After 4 months of feeding, liver, colon, and colon mucosal scrapings were collected from four pigs in each of the four dietary groups. Colonic lipid peroxidation, measured as thiobarbituric acid reacting substances (TBARS), was increased by both the high iron (P< 0.0008) and phytase (P< 0.04) supplementation. Both TBARS and F2-isoprostanes, an in vivo marker of lipid peroxidation, in colonic mucosa were affected by dietary levels of iron (P< 0.03). Mean hepatic TBARS in pigs fed the phytase-supplemented, high iron diet was 43%-65% higher than that of other groups although the differences were nonsignificant. Moderately high dietary iron induced hepatic glutathione peroxidase activity (P= 0.06) and protein expression, but decreased catalase (P< 0.05) in the colonic mucosa. In conclusion, intrinsic phytate in corn and soy was protective against lipid peroxidation in the colon associated with a moderately high level of dietary iron.

Animals↗
PubMed1999

Unanticipated heterogeneity in growth rate and virulence among Candida albicans AAF1 null mutants.

The disruption of a specific gene in Candida albicans is commonly used to determine the function of the gene product. We disrupted AAF1, a gene of C. albicans that causes Saccharomyces cerevisiae to flocculate and adhere to endothelial cells. We then characterized multiple heterozygous and homozygous mutants. These null mutants adhered to endothelial cells to the same extent as did the parent organism. However, mutants with presumably the same genotype revealed significant heterogeneity in their growth rates in vitro. This heterogeneity was not the result of the transformation procedure per se, nor was it caused by differences in the expression or function of URA3, a marker used in the process of gene disruption. The growth rate among the different heterozygous and homozygous null mutants was positively correlated with in vivo virulence in mice. It is possible that the variable phenotypes of C. albicans were due to mutations outside of the AAF1 coding region that were introduced during the gene disruption process. These results indicate that careful phenotypic characterization of mutants of C. albicans generated through targeted gene disruption should be performed to exclude the introduction of unexpected mutations that may influence pathogenicity in mice.

Alleles↗
PubMed1999

High incidence of persistent primitive arteries in moyamoya and quasi-moyamoya diseases.

This study investigated the incidences of persistent primitive arteries in patients with moyamoya disease, unilateral moyamoya disease, and quasi-moyamoya disease. Cerebral angiograms of 50 patients (39 moyamoya disease patients, 6 unilateral moyamoya disease patients, and 5 quasi-moyamoya disease patients) were retrospectively reviewed. There were 35 females and 15 males, aged from 3 to 63 years (mean 27.4 years). Persistent primitive carotid-basilar artery anastomoses were observed in three patients: primitive hypoglossal artery in one moyamoya disease patient, primitive trigeminal artery variant in one unilateral moyamoya disease patient, and an anastomosis between the accessory meningeal artery and the anterosuperior cerebellar artery in one quasi-moyamoya disease patient. The ophthalmic artery originated from the middle meningeal artery in three moyamoya and two quasi-moyamoya disease patients. The incidence of the persistent primitive arteries is significantly higher in patients with moyamoya disease (10.7%) and quasi-moyamoya disease (60%) than in patients with other disease (0.67%) (p < 0.001), so congenital factors may be important in the pathogenesis of moyamoya disease.

Adolescent↗
PubMed1999

Local alpha-bungarotoxin-sensitive nicotinic receptors modulate hippocampal norepinephrine release by systemic nicotine.

Previous studies have shown that nicotinic receptors (NAChRs) accessible from the cerebral aqueduct of the brainstem mediate the hippocampal norepinephrine (NE) release induced by i.v. nicotine. The present study was designed to investigate the role of hippocampal NAChRs in this process. Nicotinic antagonists were microinjected or microdialyzed into the hippocampus (HP) before administering nicotine (0.09 mg/kg over 60 s, i.v.) to freely moving rats. alpha-Bungarotoxin (0.3 nmol by microinjection) blocked nicotine-induced hippocampal NE release by 47% (p <.05) and abolished the effect of 0.065 mg/kg nicotine. Methyllycaconitine (1.4-5.6 mM in the dialysate) inhibited the stimulatory effect of nicotine 0.09 mg/kg by 48 to 75% (p <.05). In contrast, mecamylamine (2.9-5.8 mM) and dihydro-beta-erythroidine (7-14 mM) were completely ineffective. The role of hippocampal NAChRs was demonstrated further by selectively desensitizing these receptors before the systemic infusion of nicotine. To do so, the HP was pretreated with nicotine (0.1 mM) delivered through the microdialysis probe; this concentration was calculated to yield tissue concentrations similar to those produced by the systemic infusions of nicotine. Dialyzing this concentration of nicotine into the HP inhibited the NE response to i.v. nicotine by 34% (p <.05), and 1.0 mM nicotine reduced the response by 40%. These studies indicate that alpha-bungarotoxin-sensitive hippocampal NAChRs, probably containing alpha7 subunits, modulate hippocampal NE release because of systemic nicotine.

Animals↗