Biomedical subjects

X Fu

Publications and source records attributed to X Fu.

At least 37 records · Page 2Linked to original sources

PubMed2001

Reproducibility of in vivo brain measures of 5-HT2A receptors with PET and.

The test/retest reproducibility of brain measures of 5-HT2A receptors with positron emission tomography (PET) and [18F]deuteroaltanserin was examined in a group of eight healthy human subjects. PET measures of 5-HT2A receptors were obtained under an equilibrium paradigm, with a 40-min PET acquisition starting approximately at 300 min (308+/-11 min) after bolus plus constant infusion of the radiotracer. Three brain outcome measures were obtained at equilibrium, V(3) (ratio of specific brain uptake to free parent plasma concentration of radiotracer), V(3)' (ratio of specific brain uptake to total parent plasma concentration) and RT (ratio of specific to non-displaceable brain uptakes). V(3)' and RT had high test/retest reproducibility, as measured by mean intra-subject% change for cortical brain areas of 14.1 and 11.0%, respectively. They also had high reliability, as measured by mean intra-class correlation coefficients (ICC) for cortical brain areas of 0.86 and 0.88, respectively. V(3) had low test/retest reproducibility, due to high variability in the measures of free parent tracer in plasma. This study supports the feasibility of equilibrium imaging of 5-HT2A receptors with PET and [18F]deuteroaltanserin. The equilibrium imaging method with [18F]deuteroaltanserin allows a single acquisition and blood measurement to provide an image whose pixel values equal a receptor volume of distribution. Since the single image pixel values are proportional to receptor densities, the images can be used in pixel-by-pixel statistical methods, such as SPM, to assess the distribution and density of 5-HT2A receptors in neuropsychiatric disorders.

Adult↗

PubMed2001

The MinE ring required for proper placement of the division site is a mobile structure that changes its cellular location during the Escherichia coli division cycle.

Placement of the division site at midcell in Escherichia coli requires the MinE protein. MinE acts by imparting topological specificity to the MinCD division inhibitor, preventing the inhibitor from acting at the midcell site while permitting it to block division at other unwanted sites along the length of the cell. It was previously shown that MinE assembled into a ring structure that appeared to be localized near midcell, apparently explaining the ability of MinE to specifically counteract MinCD at midcell. We report here that the MinE ring is not fixed in position near midcell but is a dynamic structure that undergoes a repetitive cycle of movement first to one cell pole and then to the opposite pole. Taken together with studies of the dynamic behavior of the MinD protein, the results suggest that the topological specificity of division site placement may not involve a localized action of MinE to counteract the MinCD division inhibitor at midcell but rather the ability of MinE to move the division inhibitor away from midcell and to the cell poles.

Adenosine Triphosphatases↗

PubMed2001

Mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) variants in American and Japanese populations.

M6P/IGF2R encodes a multifunctional protein involved in lysosomal enzyme trafficking, fetal organogenesis, tumor suppression, and cytotoxic T cell-induced apoptosis. M6P/IGF2R is imprinted and expressed only from the maternally inherited allele in marsupials and rodents. In contrast, humans were initially reported to differ from the imprinted mammalian orders by not having an imprinted M6P/IGF2R; however, some studies now suggest M6P/IGF2R imprinting may be a human polymorphic trait. Mutational and functional evidence are consistent with M6P/IGF2R also being a tumor suppressor in human colon, liver, lung, breast, and ovarian cancers. M6P/IGF2R expression is also pathologically downregulated following mammalian in vitro embryo culture, resulting in fetal overgrowth and "large offspring syndrome." Therefore, the M6P/IGF2R imprint status in humans is an unresolved question that critically impacts upon biological issues ranging from human cancer predisposition to evolution. Attempts to further characterize the imprint status of human M6P/IGF2R and loss of heterozygosity at this locus in cancer have been hindered by a lack of readily usable polymorphisms. To facilitate these genetic analyses, we have screened American and Japanese populations for M6P/IGF2R single nucleotide polymorphisms (SNPs). We have identified nine novel SNPs intragenic to human M6P/IGF2R, and have described experimental conditions for their optimal use. Three identified amino-acid variants in the M6P/IGF2R ligand-binding domains may be under selection in humans.

Alleles↗

PubMed2001

Delivery of herpes simplex virus vectors through liposome formulation.

Viral vectors have been widely used as gene delivery vehicles for both experimental and clinical investigations. Although these vectors are capable of achieving high gene transduction efficiency in vitro, one of the major limitations facing the therapeutic viral vectors is that the preexisting host anti-vector immunity can substantially reduce their transduction efficiency in vivo. This is especially of concern when the therapeutic remedy requires repeated systemic administration. Here we report the delivery of herpes simplex virus (HSV) derived vectors through liposome formulation. In these studies, we have prepared HSV vectors in three different forms for liposome formulation: purified viral DNA (obtained from a bacterial artificial chromosome containing an infectious HSV genome), HSV capsids, and intact viral particles. All three forms of HSV were readily transfected into cultured cells and infectious virus was efficiently generated. Furthermore, introduction of HSV vectors as DNA/liposome complexes improved in vivo transduction efficiency, by effectively evading the host anti-HSV immunity during systemic administration. We conclude that viral vectors such as HSV can be systemically delivered through liposome formulation for safe and repeated administration for gene transduction or oncolytic purposes.

Alkaline Phosphatase↗

PubMed2001

Neutralization of Gro alpha and macrophage inflammatory protein-2 attenuates renal ischemia/reperfusion injury.

Previous studies have provided strong evidence for a role for neutrophils in mediating pathology during reperfusion of ischemic tissues. CXC chemokines including interleukin-8, KC/Gro alpha, and macrophage inflammatory protein (MIP)-2, direct neutrophils to tissue sites of inflammation. In the current study we tested the efficacy of antibodies to KC/Gro alpha and MIP-2 in inhibiting neutrophil infiltration into kidneys during reperfusion after 1 hour of warm ischemia using a mouse model. KC mRNA and protein were produced within 3 hours after reperfusion of the ischemic kidneys. MIP-2 mRNA and protein were twofold to fourfold lower than KC and were at low levels until 9 hours after reperfusion. Only 60% of mice subjected to ischemia/reperfusion injury survived to day 3 after reperfusion. Treatment with rabbit neutralizing antibodies to both KC and MIP-2 inhibited neutrophil infiltration into ischemic kidneys during reperfusion, restored renal function as assessed by decreased serum creatinine and urea nitrogen levels to near normal levels, and resulted in complete survival of treated animals. Finally, treatment with both antibodies significantly reduced histologically graded pathology of kidneys subjected to ischemia/reperfusion injury. Collectively, the results indicate the efficacy of neutralizing the chemokines directing neutrophils into ischemic kidneys during reperfusion to inhibit this infiltration and attenuate the resulting pathology.

Animals↗

PubMed2001

Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 genea from human fetal brain.

Short-chain dehydrogenases/reductases (SDR) constitute a large protein family of NAD(P)(H)-dependent oxidoreductase. They are defined by distinct, common sequence motifs and show a wide range of substrate specialisms. By large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a novel human SDR-type dehydrogenase/reductase gene named Dehydrogenase/reductase (SDR family) member 1 (DHRS1). The DHRS1 cDNA is 1411 base pair in length, encoding a 314-amino-acid polypeptide which has a SDR motif. Northern blot reveals two bands, of about 0.9 and 1.4 kb in size. These two forms are expressed in many tissues. The DHRS1 gene is localized on chromosome 14q21.3. It has 9 exons and spans 9.2 kb of the genomic DNA.

Amino Acid Sequence↗

PubMed2001

Substrate-induced activation of a trapped IMC-mediated protein folding intermediate.

While several unfolded proteins acquire native structures through distinct folding intermediates, the physiological relevance and importance of such states in the folding kinetics remain controversial. The intramolecular chaperone (IMC) of subtilisin was used to trap a partially folded, stable crosslinked intermediate conformer (CLIC) through a disulfide bond between mutated IMC and subtilisin. The trapped CLIC contains non-native interactions. Here we show that CLIC can be induced into a catalytically active form by incubating it with small peptide substrates. The structure and catalytic properties of the activated crosslinked intermediate conformer (A-CLIC) differ from those of the fully folded enzyme in that A-CLIC lacks any endopeptidase activity toward a large protein substrate. Our results show that a disulfide-linked partially folded protein can be induced to acquire catalytic activity with a substrate specificity that is different from completely folded subtilisin. These results also suggest that protein folding intermediates may also participate in catalytic reactions.

Binding Sites↗

PubMed2001

Expression of Arabidopsis GAI in transgenic rice represses multiple gibberellin responses.

Bioactive gibberellins (GAs) are essential endogenous regulators of plant growth. GA signaling is mediated via GAI, a nuclear member of the GRAS family of plant transcription factors. Previous experiments have suggested that GAI is a GA-derepressible repressor of plant growth. Here we test this hypothesis by examining the effects of the expression of Arabidopsis GAI in transgenic Basmati rice. High-level expression of GAI caused dwarfism and reduced GA responses, and the strength of this effect was correlated with the level of transgene expression. In particular, the expression of GAI abolished the GA-mediated induction of rice aleurone alpha-amylase activity, thus implicating GAI orthologs in the well-characterized cereal aleurone GA response. The GA derepressible repressor model predicts that high-level expression of GAI should confer dwarfism, and these observations are consistent with this prediction.

Arabidopsis↗

PubMed2001

Isomerization of a uniquely designed amplicon during herpes simplex virus-mediated replication.

Herpes simplex virus (HSV) type 1 DNA isomerization was studied using a uniquely designed amplicon that mimics the viral genomic structure. The results revealed that amplicon concatemers frequently contain adjacent amplicon units with their segments in opposed orientations. These unusual concatemers were generated through homologous recombination, which does not require HSV DNA as the source of homology.

Animals↗

PubMed2001

Extrahepatic expression of apolipoprotein A-II in mouse tissues: possible contribution to mouse senile amyloidosis.

Apolipoprotein A-II (apoA-II), an apolipoprotein in serum high-density lipoprotein, is a precursor of mouse senile amyloid fibrils. The liver has been considered to be the primary site of synthesis. However, we performed nonradioactive in situ hybridization analysis in tissue sections from young and old amyloidogenic (R1.P1-Apoa2C) and amyloid-resistant (SAMR1) mice and revealed that other tissues in addition to the liver synthesize apoA-II. We found a strong hybridization signal in the basal cells of the squamous epithelium and the chief cells of the fundic gland in the stomach, the crypt cells and a small portion of the absorptive epithelial cells in the small intestine, the basal cells of the tongue mucosa, and the basal cells of the epidermis and hair follicles in the skin in both mouse strains. Expression of apoA-II mRNA in those tissues was also examined by RT-PCR analysis. Immunolocalization of apoA-II protein also indicated the cellular localization of apoA-II. ApoA-II transcription was not observed in the heart. Amyloid deposition was observed around the cells expressing apoA-II mRNA in the old R1.P1-Apoa2C mice. These results demonstrate that the apoA-II mRNA is transcribed and translated in various extrahepatic tissues and suggest a possible contribution of apoA-II synthesized in these tissues to amyloid deposition.

Aging↗

PubMed2001

Loss of nm23 expression predicts distal metastases and poorer survival for breast cancer.

The nm23 gene, originally identified by differential hybridization of metastatic murine melanoma cell lines has been associated with decreased metastatic potential. In this study, we evaluated the utility of nm23 expression levels as a predictive and a prognostic biomarker for distal metastases and poor survival in a Chinese cohort of 168 breast cancer patients. Our study indicates that high nm23 expression is associated with older age (older than 35 years) and smaller tumor size. There is no statistically significant association between nm23 expression and pathologic type or axillary metastasis. High nm23 expression is associated with the absence of distal metastases. Nearly 80% of women with high nm23 expression are alive after 10 years compared to 25% with low expression; at five years the cumulative survival proportions are 86% and 46%, respectively. The Cox model for survival indicates that controlling for tumor size and presence of axillary metastases at diagnosis, the hazard for women with low nm23 expression is nearly 4 times that of women with high nm23 expression. Low nm23 expression is predictive of distal metastases and appears to be a risk factor that is independent of the presence or absence of positive axillary nodes at diagnosis.

Adult↗

PubMed2001

[Photocatalytic degradation of bromomethane on sol-gel-derived SO4(2-)/TiO2].

SO4(2-)/TiO2 photocatalysts were prepared by sol-gel method and characterized by X-ray diffraction (XRD), FTIR spectroscopy and N2 sorption analysis applying BET method. Photocatalytic decomposition of CH3Br in air stream was studied over SO4(2-)/TiO2 photocatalysts under the different reaction conditions. The results showed that the addition of SO4(2-) to TiO2 greatly enhanced its structural and photocatalytic properties. The optimum concentration of SO4(2-) on TiO2 was 9% wt and the best calcination temperature was 450 degrees C. Moreover, the sulfated TiO2(SO4(2-)/TiO2) exhibited excellent stability of activity under the moist reaction condition. When the reaction temperature was below 85 degrees C, the reactivity of bromomethane was enhanced with increasing reaction temperatures, and the apparent Arrehenius activation energy was 19.6 kJ.mol-1. In the reaction temperature range of 85 degrees C-105 degrees C, the apparent Arrehenius activation energy was zero.

Catalysis↗

PubMed2001

Bringing a family practice model of health to the People's Republic of China.

The health care system in the People's Republic of China (PRC) is undergoing a major transition that has made the government revise its approach to how medicine is taught and practiced. Family medicine, which provides a generalist approach to medical care, is at the forefront of this transition. This article reviews the recent history of medical education in the PRC, including the establishment of the discipline of family medicine in the mid 1980s, and factors promoting development of family medicine. These include the movement away from government-subsidized health care in hospital settings, the aging population, increased urbanization, increasing incidence of infectious diseases, and rising health care costs. We conclude from observations made in the PRC and from a review of secondary sources that family medicine in China is in its infancy. The value of understanding the role that family medicine plays within China's changing health care system is that we gain a broader perspective of the variety and growing international importance of family practice as a profession.

Delivery of Health Care↗

PubMed2001

[mRNA and protein expression of three growth-related factors and their possible signal transduction pathways in wound healing].

OBJECTIVE: To observe the time course and tissue distribution of c-fos, c-myc and basic fibroblast growth factor(bFGF) genes and their proteins in burned skin, and explore the possible network regulation mechanisms of c-fos, c-myc and bFGF in wound healing and the role of the protein kinase C pathway involved in signal transduction among these growth-related factors. METHODS: The study was carried out on 188 Wistar rats. Animal model with 30% partial thickness scald injury was made and all rats were randomly divided into several groups: normal control (n = 8), injured control (n = 36), anti-c-fos (n = 36), bFGF (n = 36), 1-5-Isoquinolinyl-sulfony-2methylpiperazine (H7), and 2, 3-Butanedione monoxime (BDM) (n = 36). In situ hybridization, reverse transcription polymerase chain reaction (RT-PCR) and streptavidin peroxidase (SP) immunohistochemistry methods were used to detect the gene and protein expression of c-fos, c-myc and bFGF in the wounded tissues. RESULTS: (1) The first appeared induction of growth-related gene was c-fos, the second bFGF, and the last c-myc. They were peaked at 3 h, 1 d and 3 d postburn with values of 14.5 +/- 1.3, t = 13.306; 0.15 +/- 0.04, t = 3.460 and 0.11 +/- 0.05, t = 2.292, respectively (P < 0.05). (2) Treatment with c-fos antibody decreased the expression of these three growth-related factors when compared with that in the controls. There were a 80% decrease in c-myc and a 85% decrease in bFGF. (3) Treatment with H7 inhibited the gene and protein expression of c-fos and bFGF. The peak times of c-myc gene and protein were delayed to 6 hours post injury. Treatment with BDM induced an earlier expression of c-myc mRNA at 6 hours, and increased the gene and protein expressions of c-fos and bFGF. The total amount of their values was increased to 0.23 +/- 0.07, t = 2.942 and 0.69 +/- 0.07, t = 5.134 (P < 0.01). CONCLUSIONS: Thermal injury can induce a series of growth-related gene expression showing a phasic control and regional distribution. c-fos plays an important role in wound healing process. Protein kinase C pathway may repair wound.

Animals↗

PubMed2001

Expression of oncoproteins c-fos and c-jun in hypertrophic scars and chronic dermal ulcers and their regulation of basic fibroblast growth factor.

OBJECTIVE: To explore the characteristics of oncoprotein expression of c-fos and c-jun in hypertrophic scars and chronic dermal ulcers and their regulation of basic fibroblast growth factor (bFGF). METHODS: Tissues of hypertrophic scars (n = 8), chronic dermal ulcers (n = 8) and normal skin (n = 5) were taken from 21 patients with burns and chronic dermal ulcers in operation. The ABC immunohistochemical method was used to characterize the gene product expression of c-fos, c-jun and bFGF in the above tissues. RESULTS: In normal skin, both c-fos and c-jun protein expression and bFGF protein expression were observed. The signals of both oncoproteins were localized mainly in subcutaneous fibroblasts, but, positive expression of the bFGF protein was mainly in keratinocytes. In hypertrophic scars, positive expression of both oncoproteins could be found mainly in fibroblasts, but bFGF was mainly in fibroblasts and endothelial cells. In chronic dermal ulcers, endothelial cells, some of inflammatory cells and fibroblasts were positive for both of oncoproteins, but the expression of bFGF was only seen in fibroblasts and endothelial cells. CONCLUSIONS: The results indicate that the interaction between both oncoproteins and bFGF exists, and the regulating action between protooncogenes and bFGF is a major course in wound healing. The different expressions of c-fos and c-jun gene products play an important role in regulate bFGF action, thus affecting wound healing.

Chronic Disease↗

PubMed2001

Expression characteristics of c-fos, c-myc and bFGF in early burn tissue.

OBJECTIVE: To investigate the sequence and characteristics of expression of proto-oncogenes, c-fos, c-myc and endogenous basic fibroblast growth factor (bFGF), in burn tissue from rats. METHODS: A partial thickness burn of 30% TBSA was created on the backs of Wistar rats. Immunohistochemistry was used to detect the expression of these proteins in normal and burned skin at 3 hours, 6 hours, 1 day, 3 days, 7 days and 14 days postburn. RESULTS: Expression of c-fos, c-myc and bFGF was induced by the burn, but these three proteins showed different expression levels in sequence and distribution. Expression of c-fos increased and peaked at 3 hours postburn. Stain positive granules were distributed mainly in the cytoplasm of basal cells and the nuclei of fibroblasts. The expression of bFGF protein increased at 6 hours and peaked at 1 day postburn; it was distributed in the cytoplasm of fibroblasts. c-myc protein peaked at 3 days postburn and was also distributed in the cytoplasm of fibroblasts. CONCLUSIONS: Thermal injury can induce c-fos, c-myc and bFGF expression and show phasic control and regional distribution. The phasic expression of these three proteins indicates that there maybe a regulatory relationship between proto-oncogenes and growth factors in early burn. This may play an important role in late tissue repair.

Animals↗

PubMed2001

[Expression of nm23 in breast cancer: correlation with distant metastasis and prognosis].

OBJECTIVE: To investigate the relationship between expression of nm23 gene and distant metastasis and prognosis in breast cancer. METHODS: To detect nm23 protein expression in 101 patients with breast cancer by means of immunohistochemistry and nm23 mRNA expression in 68 patients with breast cancer by RT-PCR. RESULTS: Expression of nm23 gene was inversely correlated with distant metastasis and lymph node metastasis. Among 9 patients with negative node but with distant metastasis, 7 had low expression of nm23. In 29 patients with positive nodes but without distant metastasis, 24 had high expression of nm23, while 6 of 6 patients with positive nodes and distant metastasis expressed high levels of nm23 mRNA. CONCLUSION: Expression of nm23 gene, tumor size and status of axillary lymph node are independent prognostic indicators to breast cancer prognosis.

Adult↗

PubMed2001

[Clinical and pathologic analysis of Sjögren's syndrome with renal impairment: a report of 84 cases].

OBJECTIVE: To further study the renal damage of Sjögren's syndrome (SS) and its clinical and pathologic characteristics with biopsy and recent technology. METHODS: 84 patients of SS with renal impairment from 1993 to 1999 were analyzed by routine, immunoassay, tubular function and biopsy examination. RESULTS: 55 of the 84 cases presented with renal tubular acidosis (RTA), 5 with diabetes insipidus and 3 with hypokalemic paralysis. Glomerulopathy occurred in 22 cases (nephrotic syndrome 12, glomerulonephritis 10) and mild renal failure (RF) was found in 14. 69.1% of the patients had hypergamma-globulinemia. 64.3% and 44.1% of the patients showed positive anti SS-A and anti SS-B. In 37 renal biopsy specimens 21 showed chronic interstitial nephritis (CIN) with extensive lymphoplasmic cell infiltration and tubular atrophy. 10 of the 37 specimens revealed lupus nephritis (LN, type III and IV) and 5 mesangial proliferative glomerulonephritis (MsPGN). With immunofluorescence tests, no positive findings were seen in most of the specimens, but deposition of IgA, IgM or C(3) was seen in some patients. IgG deposits in the interstitial lymphoplasmic cells were found in 1 patient. 25 patients were treated with prednisone combined with cytoxan (CTX). In 14 patients with renal failure, serum creatinine level returned to normal after treatment. CONCLUSION: Renal impairment may be the presenting or predominant feature in SS. The major clinical manifestations are RTA and GN. Treatment with prednisone may decrease the infiltration of lymphoplasmic cells in the interstitium, improve the renal function and correct RTA.

Adolescent↗