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Biomedical subjects

F Chu

Publications and source records attributed to F Chu.

At least 19 recordsLinked to original sources
PubMed2007

Characterization of Anaplasma phagocytophilum major surface protein 5 and the extent of its cross-reactivity with A. marginale.

Major surface protein 5 (Msp5) of Anaplasma marginale is highly conserved in the genus Anaplasma and the antigen used in a commercially available competitive enzyme-linked immunosorbent assay (cELISA) for serologic identification of cattle with anaplasmosis. This study analyzes the degrees of conservation of Msp5 among various isolates of Anaplasma phagocytophilum and the extent of serologic cross-reactivity between recombinant Msp5 (rMsp5) of Anaplasma marginale and A. phagocytophilum. The msp5 genes from various isolates of A. phagocytophilum were sequenced and compared. rMsp5 proteins of A. phagocytophilum and A. marginale were used separately in an indirect ELISA to detect cross-reactivity in serum samples from humans and dogs infected with A. phagocytophilum and cattle infected with A. marginale. Serum samples were also tested with a commercially available competitive ELISA that uses monoclonal antibody ANAF16C1. There were 100% sequence identities in the msp5 genes among all of the A. phagocytophilum isolates from the United States and a horse isolate from Sweden. Sheep isolates from Norway and dog isolates from Sweden were 99% identical to one another but differed in 17 base pairs from the United States isolates and the horse isolate. Serologic cross-reactivity was identified when serum samples from cattle infected with A. marginale were reacted with rMsp5 of A. phagocytophilum and when serum samples from humans and dogs infected with A. phagocytophilum were reacted with rMsp5 of A. marginale in an indirect-ELISA format. Serum samples from dogs or humans infected with A. phagocytophilum did not cross-react with rMsp5 of A. marginale when tested with the commercially available cELISA. These results suggest that rMsp5 of A. phagocytophilum is highly conserved among United States and European isolates and that serologic distinction between A. phagocytophilum and A. marginale infections cannot be accomplished if rMsp5 from either organism is used in an indirect ELISA.

Anaplasma marginale↗
PubMed2006

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma: non-mucinous tumour associated with an improved survival.

AIMS: Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has been reported as a treatment option for patients with peritoneal carcinomatosis from colorectal carcinoma. METHODS: Thirty patients with colorectal peritoneal carcinomatosis underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy. All appendiceal cancers were excluded. All patients were followed until January 2006 or death. Univariate analysis was performed to evaluate significant prognostic factors for overall survival, defined from the time of surgery. RESULTS: There were 13 male patients. The mean age at the time of surgery was 54years. There was no hospital mortality. The mean duration of hospital stay was 27days. The overall median survival was 29months, with 1- and 2-year survival of 72% and 64%, respectively. Twenty-one patients had complete cytoreduction and their 1- and 2-year survival rates were 85% and 71%, respectively. Univariate analysis demonstrated that patients with non-mucinous colorectal adenocarcinoma, Peritoneal Cancer Index (PCI) < or =13, and complete cytoreduction were associated with an improved survival. CONCLUSIONS: This study reported on 30 patients who underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. Patients with mucinous tumour had relatively more extensive intraperitoneal disease. Non-mucinous colorectal adenocarcinoma, PCI < or =13, and complete cytoreduction were associated with an improved survival.

Adenocarcinoma↗
PubMed2006

Single centre experience of liver resection for hepatocellular carcinoma in patients outside transplant criteria.

INTRODUCTION: To report analysis of our results of liver resection for HCC outside the transplant criteria with preserved liver function. METHODS: Between January 1990 and March 2005, 279 patients with HCC were seen at our institution and entered into a prospective database. There were 51 patients who did not fulfill the transplant criteria and underwent partial hepatectomy. Survival was determined by Kaplan-Meier analysis. RESULTS: The median tumour size was 10.0 cm with a range of 3-20 cm. Twenty-nine patients had solitary tumours and 21 patients had two or more liver tumours, with four patients whose tumours were less than 5 cm in maximal diameter. Ten patients had bilobar disease. The 30-day mortality was 8%. The 1-, 3- and 5-year overall survival was 63, 40 and 33%, respectively, and the median survival was 16.6 months. Fifteen potential variables were analysed as potential predictors of adverse outcome. Multivariate analysis showed Child-Pugh classification, presence of cirrhosis, rupture on presentation and tumour histology to be independent prognostic factors on survival. CONCLUSION: Partial hepatectomy in patients with advanced HCC who are ineligible for transplantation can be performed safely and can achieve a 5-year survival of 33%.

Aged↗
PubMed2006

The role of histone acetylation versus DNA damage in drug-induced senescence and apoptosis.

The present study was undertaken to determine the significance of histone acetylation versus DNA damage in drug-induced irreversible growth arrest (senescence) and apoptosis. Cellular treatment with the DNA-damaging drugs doxorubicin and cisplatin or with the histone deacetylase inhibitor trichostatin A, led to the finding that all the three drugs induced senescence at concentrations significantly lower than those required for apoptosis. However, only doxorubicin and cisplatin induced activation of H2AX, a marker for double-strand break formation. Interestingly, this occurred mainly at apoptosis and not senescence-inducing drug concentrations, suggesting that non-DNA-damage pathways may be implicated in induction of senescence by these drugs. In agreement with this, chromatin immunoprecipitation experiments indicated that doxorubicin was able to induce acetylation of histone H3 at the promoter of p21/WAF1 only at senescence-inducing concentrations. Collectively, these findings suggest that alteration of chromatin structure by cytotoxic drugs may represent a key mediator of senescence.

Acetylation↗
PubMed2006

Siva-1 negatively regulates NF-kappaB activity: effect on T-cell receptor-mediated activation-induced cell death (AICD).

Ligation of TCRs on stimulated T cells leads to activation-induced cell death (AICD) resulting in the downregulation of immune responses, a process essential for T-cell homeostasis. In this study, using transformed T-cell lines such as Jurkat and Do11.10 as cellular models of TCR-mediated AICD, we have demonstrated that the proapoptotic protein Siva-1 is required for TCR-induced apoptosis. Knockdown of Siva-1 rendered T cells specifically resistant to anti-CD3 but not Fas-induced apoptosis. Further, we observed that in Siva-1 knockout Jurkat cells, TCR-mediated activation of the canonical and non-canonical limbs of the NF-kappaB pathway are significantly enhanced as reflected by elevated nuclear levels of p65 and RelB, respectively. In addition, loss of endogenous Siva-1 also resulted in the enhanced expression of NF-kappaB- responsive anti-apoptotic genes such as Bcl-xL and c-FLIP. Interestingly, the c-FLIP(short) was detected only in TCR-ligated Siva-1 knockdown Jurkat cells. These results demonstrate a significant role for endogenous Siva-1, through its inhibitory effect on NF-kappaB activity, in TCR-mediated AICD with implications in peripheral tolerance, T-cell homeostasis and cancer.

Apoptosis↗
PubMed2006

Metabolism and excretion of imrecoxib in rat.

The metabolism and excretion of imrecoxib, a novel and moderately selective cyclooxygenase-II inhibitor, were investigated in rat. The structures of metabolites were identified by mass spectrometry (MSn) and nuclear magnetic resonance. Metabolic profiles of imrecoxib in urine, bile and faeces were obtained by HPLC and LC/MSn, and cumulative excretion was determined by LC/MSn. Imrecoxib was extensively metabolized in rat after intravenous administration, with less than 2% of the dose excreted as parent drug in either urine or faeces. The major metabolic pathway was that the 4'-methyl group of imrecoxib was first oxidized to the 4'-hydroxymethyl metabolite (M4), followed by additional oxidation to 4'-carboxylic acid metabolite (M2). The dihydroxylated metabolite, 4'-hydroxymethyl-5-hydroxyl imrecoxib (M3), was further oxidized to 4'-hydroxymethyl-5-carbonyl metabolite (M5), and glucuronide conjugates of M2-4 were formed. After intravenous (5 mg kg-1) administration, the majority of the dose was recovered in the faeces. The dose was primarily excreted as the carboxylic acid metabolite in addition to the 4'-hydroxymethyl metabolite. The carboxylic acid metabolite was mainly excreted in faeces, while the 4'-hydroxymethyl metabolite was mainly excreted in urine.

Animals↗
PubMed2005

Persistent shedding of viable SARS-CoV in urine and stool of SARS patients during the convalescent phase.

In order to further the present knowledge of the emerging severe acute respiratory syndrome-associated coronavirus (SARS-CoV), 486 different specimens from 54 patients with a clinical diagnosis of SARS were investigated for the presence of viral RNA, and 314 plasma specimens of 73 patients were examined for IgM and IgG antibodies specific against SARS-CoV using an indirect ELISA. Viral RNA was detectable in 28 of the 54 patients tested. Cumulative data showed that 67 of the 73 SARS patients demonstrated seroconversion by week 5 of illness. In contrast, only 1 of 278 healthy subjects enrolled in the study was found to be positive for the IgG antibody. Coexistence of viral RNA in plasma and specific antibodies was simultaneously observed over three consecutive weeks in two critical cases. In three convalescent patients in particular, cultivable SARS-CoV was detected in stool or urine specimens for longer than 4 weeks (29-36 days). These findings suggest that SARS-CoV may remain viable in the excretions of convalescent patients.

Adult↗
PubMed2005

Recurrent acute heart failure caused by sliding hiatus hernia.

The case is reported of a 75 year old woman who presented with recurrent nocturnal episodes of acute pulmonary oedema. The cause was uncertain as she had normal cardiothoracic ratio on chest radiography and normal left ventricular systolic and diastolic function by transthoracic echocardiogram. Another transthoracic echocardiogram was repeated when she was recumbent for an hour and had a full stomach. It showed a striking finding of severe left atrial compression by an external structure. Computed tomography of the thorax showed an intrathoracic mass behind the left atrium causing external compression of the left atrium suggestive of a sliding hiatus hernia. Cardiac catheterisation confirmed the diagnosis by showing a pronounced rise of pulmonary capillary wedge pressure in the recumbent position compared with the sitting up position.

Aged↗
PubMed2004

The Siva-1 putative amphipathic helical region (SAH) is sufficient to bind to BCL-XL and sensitize cells to UV radiation induced apoptosis.

The human Siva gene is localized to chromosome 14q32-33 and gives rise to the full-length predominant form, Siva-1 and a minor alternate form, Siva-2 that appears to lack the proapoptotic properties of Siva-1. Our recent work has shown that the missing region in Siva-2 encodes a unique twenty amino acid putative amphipathic helical region (SAH, residues 36-55 in Siva-1). Despite the fact that Siva-1 does not belong to the BCL-2 family, it specifically interacts with the anti-apoptotic protein BCL-XL and sensitizes MCF7 breast cancer cells expressing BCL-XL to UV radiation induced apoptosis. Deletion mutagenesis has mapped the necessary region to the SAH in Siva-1. In this paper we demonstrate that the SAH region in Siva-1 is sufficient to specifically interact with the anti-apoptotic members of the BCL2 family such as BCL-XL and BCL-2 but not its apoptotic member BAX. Using transient transfections and direct microinjection of synthetic SAH peptides, we also demonstrate that the SAH region is sufficient to inhibit the BCL-XL mediated cell survival and render MDA-MB-231 and MCF7 breast cancer cells expressing BCL-XL highly susceptible to UV radiation induced apoptosis. The underlying mechanism of action of SAH mediated inhibition of BCL-XL (and/or BCL2) cell survival appears to be due to loss of mitochondrial integrity as reflected in enhanced cytochrome c release leading to the activation of caspase 9 and finally caspase 3.

Actins↗
PubMed2001

Prospects for targeting protein kinase C isozymes in the therapy of drug-resistant cancer--an evolving story.

The seminal discovery in 1988 that selective protein kinase C (PKC) activators induce multidrug resistance (MDR) in human cancer cells spawned several years of intensive investigations; these studies were primarily directed at the question of whether isozyme-selective PKC antagonism could reverse MDR phenotypes produced in cancer cells by P-glycoprotein and other ATP-binding cassette (ABC) transporters. The first section of this commentary provides a succinct overview of those studies. In the second section, we evaluate why the enthusiasm for studies of the involvement of PKC in transport-related drug resistance is currently diminished, and we offer an assessment of whether the PKC/MDR field should be revisited. The final section of the commentary highlights recent developments in studies of PKC targeting in experimental cancer therapeutics, which continues to be a vibrant field. Highlights include the sensitization of cancer cells to radiation- and drug-induced apoptosis by PKC inhibition.

Antineoplastic Agents↗
PubMed2001

Potent inactivation of representative members of each PKC isozyme subfamily and PKD via S-thiolation by the tumor-promotion/progression antagonist glutathione but not by its precursor cysteine.

We recently established that S-glutathiolation of cPKCalpha fully inactivates the isozyme, at a stoichiometry of approximately 1 mol GSH/mol cPKCalpha. In this report we demonstrate that, in addition to cPKCalpha, six other PKC isozymes that are representative of the three subfamilies within the PKC family (cPKCbeta1, cPKCbeta2 and cPKCgamma, nPKCdelta and nPKCepsilon and aPKC-zeta) are subject to inactivation by S-glutathiolation induced by the thiol-specific oxidant diamide, which induces disulfide bridge formation. Among PKD and the seven PKC isozymes examined in this report only nPKCdelta has been directly implicated as an antagonist of tumor promotion/progression, while several of the kinases have been implicated in the mediation of tumor promotion/progression. We report that of the kinases examined nPKCdelta was the most resistant to inactivation by diamide-induced S-glutathiolation. In the absence of GSH only nPKCdelta activity exhibited a biphasic response to diamide, with low diamide concentrations oxidatively enhancing nPKCdelta activity and higher concentrations inactivating the isozyme; the other seven kinases were subject to monophasic, concentration-dependent, oxidative inactivation by diamide to various extents. The results provide evidence that at least some pro-oxidant environments may support the potent inactivation of nPKCepsilon and other PKC isozymes implicated in tumor promotion/progression by the mechanisms of S-glutathiolation and, in some cases, disulfide bridge formation among the isozyme thiols, without inducing substantial nPKCdelta inactivation. The results also show that neither the seven PKC isozymes examined nor PKD are inactivated by S-cysteinylation under conditions that support potent inactivation by S-glutathiolation. This indicates that the protection that the tumor promotion/progression antagonist GSH may afford against oxidative tumor promotion/progression mechanisms by S-thiolating and inactivating PKC isozymes and PKD cannot be afforded by the metabolic GSH precursor cysteine. These observations support a role for PKC inactivation via S-glutathiolation in the mechanism of tumor promotion/progression antagonism by GSH in pro-oxidant environments.

Cysteine↗
PubMed2001

[Study on using colloidal gold immuno-dot assay to detect special antibody of hemorrhagic fever renal syndrome].

OBJECTIVE: To seek for a simple, sensitive and rapid assay to detect specific antibody of patients suffering from hemorrhagic fever renal syndrome (HFRS). METHODS: Serum anti-HFRS IgM (sIgM) and IgG (sIgG) antibody were detected in 186 patients with HFRS using colloidal gold immuno-dot assay (CGIDA), and compared with those detected with enzyme linked immunosorbant assay (ELISA) and indirect fluorescent antibody test (IFAT). Kuhuang Shenmai injection (KHSM) combined Astragalus decoction (AD) treatment was applied to 101 HFRS patients in a treated group (n = 50), and the effect of therapy was compared with that in a control group (n = 51) treated with ribarvirin and ganlixin injection. RESULTS: CGIDA showed positive sIgM antibody in 132 cases (70.9%) and positive sIgG antibody in 163 (87.1%) of the 186 HFRS patients. As compared the two groups in crossing stage, the rate of crossing shock stage in the treated group was higher than that in the control (P < 0.05). As for rate of crossing oliguria stage and from febrile stage directly developed into diuretic stage, the difference between the two groups was insignificant (P < 0.05). CONCLUSION: CGIDA shows the merits of quick, simple and convenient in detecting sIgM and sIgG antibody in HFRS patients. The effect of KHSM combined AD treatment was not significantly different from that of ribarvirin and ganlixin injection.

Adolescent↗
PubMed2000

A comparative map of the zebrafish genome.

Zebrafish mutations define the functions of hundreds of essential genes in the vertebrate genome. To accelerate the molecular analysis of zebrafish mutations and to facilitate comparisons among the genomes of zebrafish and other vertebrates, we used a homozygous diploid meiotic mapping panel to localize polymorphisms in 691 previously unmapped genes and expressed sequence tags (ESTs). Together with earlier efforts, this work raises the total number of markers scored in the mapping panel to 2119, including 1503 genes and ESTs and 616 previously characterized simple-sequence length polymorphisms. Sequence analysis of zebrafish genes mapped in this study and in prior work identified putative human orthologs for 804 zebrafish genes and ESTs. Map comparisons revealed 139 new conserved syntenies, in which two or more genes are on the same chromosome in zebrafish and human. Although some conserved syntenies are quite large, there were changes in gene order within conserved groups, apparently reflecting the relatively frequent occurrence of inversions and other intrachromosomal rearrangements since the divergence of teleost and tetrapod ancestors. Comparative mapping also shows that there is not a one-to-one correspondence between zebrafish and human chromosomes. Mapping of duplicate gene pairs identified segments of 20 linkage groups that may have arisen during a genome duplication that occurred early in the evolution of teleosts after the divergence of teleost and mammalian ancestors. This comparative map will accelerate the molecular analysis of zebrafish mutations and enhance the understanding of the evolution of the vertebrate genome.

Animals↗
PubMed2000

Genetic linkage mapping of zebrafish genes and ESTs.

Genetic screens in zebrafish (Danio rerio) have isolated mutations in hundreds of genes essential for vertebrate development, physiology, and behavior. We have constructed a genetic linkage map that will facilitate the identification of candidate genes for these mutations and allow comparisons among the genomes of zebrafish and other vertebrates. On this map, we have localized 771 zebrafish genes and expressed sequence tags (ESTs) by scoring single-stranded conformational polymorphisms (SSCPs) in a meiotic mapping panel. Of these sequences, 642 represent previously unmapped genes and ESTs. The mapping panel was comprised of 42 homozygous diploid individuals produced by heat shock treatment of haploid embryos at the one-cell stage (HS diploids). This "doubled haploid" strategy combines the advantages of mapping in haploid and standard diploid systems, because heat shock diploid individuals have only one allele at each locus and can survive to adulthood, enabling a relatively large quantity of genomic DNA to be prepared from each individual in the mapping panel. To integrate this map with others, we also scored 593 previously mapped simple-sequence length polymorphisms (SSLPs) in the mapping panel. This map will accelerate the molecular analysis of zebrafish mutations and facilitate comparative analysis of vertebrate genomes.

Animals↗
PubMed2000

Zebrafish comparative genomics and the origins of vertebrate chromosomes.

To help understand mechanisms of vertebrate genome evolution, we have compared zebrafish and tetrapod gene maps. It has been suggested that translocations are fixed more frequently than inversions in mammals. Gene maps showed that blocks of conserved syntenies between zebrafish and humans were large, but gene orders were frequently inverted and transposed. This shows that intrachromosomal rearrangements have been fixed more frequently than translocations. Duplicated chromosome segments suggest that a genome duplication occurred in ray-fin phylogeny, and comparative studies suggest that this event happened deep in the ancestry of teleost fish. Consideration of duplicate chromosome segments shows that at least 20% of duplicated gene pairs may be retained from this event. Despite genome duplication, zebrafish and humans have about the same number of chromosomes, and zebrafish chromosomes are mosaically orthologous to several human chromosomes. Is this because of an excess of chromosome fissions in the human lineage or an excess of chromosome fusions in the zebrafish lineage? Comparative analysis suggests that an excess of chromosome fissions in the tetrapod lineage may account for chromosome numbers and provides histories for several human chromosomes.

Animals↗
PubMed2000

Structural phase transitions of HfV2 at low temperatures.

We report a high-resolution synchrotron X-ray powder diffraction study on HfV(2), hafnium divanadium, at low temperatures. In this work we show, for the first time, a complete sequence of structural phase transitions of HfV(2) from cubic (Fd3m) to tetragonal (I4(1)/amd) to orthorhombic (Imma) in succession as temperature decreases. Peak splitting and extra diffraction peaks owing to lattice distortion can be clearly distinguished for the low-symmetry phases. The atomic positions and lattice parameters were obtained by Rietveld refinement. The bond lengths and angles of the HfV(2) crystal structure at the low-symmetry phases were correctly determined from the structure refinement. The face-centered cubic (Fd3m) unit cell (Z = 24) transforms to a body-centered tetragonal (I4(1)/amd) phase with a 45 degrees rotation relative to the cubic cell and with a reduced number of atoms (Z = 12) in the unit cell at a temperature of T = 112 K. The orthorhombic phase occurs at T = 102 K and it keeps the body-centered symmetry (Imma) and Z = 12 in the unit cell. The refinement results indicate that there may be a small amount of untransformed cubic phase left over in the lower symmetry phases. The abnormal thermal contraction of both tetragonal phase and orthorhombic phase marks the significance of structural change in HfV(2).

Journal Article↗
PubMed2000

[Effect of inflammatory factor and yishen huoxue xiezhuo decoction on growth of glomerular mesangial cells in rats].

OBJECTIVE: To explore the part of inflammatory factors (cytokines) and Yishen Huoxue Xiezhuo (YSHXXZ) Decoction on the proliferation of extracorporeal cultured mesangial cells (MCs) in rats. METHODS: The effects of lipopolysaccharide (LPS) and interleukin-6 (IL-6) as stimulating factors, its action on the proliferation of rat MCs were investigated by using the technique of 3H-TdR incorporation. Meanwhile, adopting serum pharmacology assay, the medicated serum of rat, containing YSHXXZ decoction was extracted and its effects on the growth of MCs were also studied. RESULTS: LPS and IL-6, in a dose-dependent and time-dependent manner, could markedly stimulate the MCS proliferation, while this stimulatory effects could be strongly antagonized by the serum containing YSHXXZ decoction. CONCLUSION: Mesangial cell is the main target cell of the action of YSHXXZ decoction, and the inhibition on MCs might be one of the mechanisms of the YSHXXZ decoction in preventing the progression of chronic glomerulonephritis.

Animals↗