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Biomedical subjects

F Xu

Publications and source records attributed to F Xu.

At least 163 records · Page 9Linked to original sources

Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children.

We examined mRNA expression and internal tandem duplication of the Fms-like tyrosine kinase 3 (FLT3) gene in haematological malignancies by reverse transcriptase-polymerase chain reaction (RT-PCR) and genomic PCR followed by sequencing. By RT-PCR, expression of FLT3 was detected in 45/74 (61%) leukaemia cell lines and the frequency of expression of FLT3 was significantly higher in undifferentiated type (B-precursor acute lymphoblastic leukaemia; ALL) than in differentiated type cell lines (B-ALL) (P = 0.0076). Using the genomic PCR method, 194 fresh samples including 87 acute myeloid leukaemias, 60 ALLs, 32 myelodysplastic syndromes (MDSs) and 15 juvenile chronic myelogenous leukaemias (JCMLs) were examined. Tandem duplication was found in 12 (13.8%) AMLs and two (3.3%) ALLs. Sequence analyses of the 14 samples with the duplication revealed that eight showed a simple tandem duplication and six a tandem duplication with insertion. Most of these tandem duplications occurred within exon 11, and two duplications occurred from exon 11 to intron 11 and exon 12. No tandem duplications of FLT3 gene were detected in MDS or JCML. The frequency of tandem duplication of FLT3 gene in childhood AML was lower than that in adult AML so far reported. All of the 12 AML patients with the duplication died within 47 months after diagnosis, whereas two ALL patients with the duplication have survived 44 and 72 months, respectively. These two ALL patients expressed both lymphoid and myeloid antigens and were considered to have biphenotypic leukaemia. These results suggest that tandem duplication is involved in ALL in addition to AML, but not in childhood MDS or JCML, and that childhood AML patients with the tandem duplication have a poor prognosis.

Acute Disease↗

[Genetic complementation group analysis of xeroderma pigmentosum patients in China].

OBJECTIVE: To establish skin fibroblast cell strains derived from Chinese xeroderma pigmentosum(XP) patients and to analyze the genetic complementation group and distribution. METHODS: From four XP patients, skin fibroblast cell strains were derived and used for the complementation group analysis by autoradiography and cell-fusion technique. RESULTS: Of the four XP patients from apparently independent families, three were assigned to group C, and one belonged to group E. This is the first report on XP-E patient in China. CONCLUSION: Based on the data from the previous 7 cases and the present 4 cases, the distribution of complementation group in Chinese XP patients known at present is: nine XP-C, one XP-F and one XP-E. Although the number of cases is still limited, XP-C appears to be more frequent in China. This forms a marked contrast to Japanese XP patients, who are dominated by XP-A with infrequent presence of XP-C.

Adolescent↗

The outcome of heregulin-induced activation of ovarian cancer cells depends on the relative levels of HER-2 and HER-3 expression.

Members of the epidermal growth factor receptor family of tyrosine kinases, including epidermal growth factor receptor, c-erbB-2 (HER-2), c-erbB-3 (HER-3), and c-erbB-4 (HER-4), can be coexpressed at different levels in nonhematopoietic tissues. Amplification and overexpression of HER-2 is found in approximately one-third of cancers that arise in the breast and ovary. In our previous studies, heregulin (HRG) and anti-HER-2 antibodies inhibited proliferation, increased invasiveness, and enhanced tyrosine autophosphorylation of SKBr3 breast cancer cells that overexpressed HER-2. In the present report, the effects of HRG and anti-HER-2 antibody have been compared in six ovarian cancer cell lines. HRG inhibited anchorage-independent growth of SKOv3 cells that overexpressed HER-2 (10(5) receptors/cell) but stimulated the growth of OVCA420, OVCA429, OVCA432, OVCA433, and OVCAR-3 cells that expressed lower levels of the receptor (10(4) receptors/cell). Thus, cell lines with a high level of HER-2 relative to HER-3 or HER-4 were growth inhibited, whereas cell lines with lower levels of HER-2 were growth stimulated by HRG. Stimulation or inhibition of clonogenic growth did not correlate with endogenous expression of HRG or with the impact of exogenous HRG on phosphorylation of HER-2, HER-3, or HER-4. Anti-HER-2 antibodies inhibited the growth of SKOv3 cells but failed to affect the growth of the other cell lines. In OVCAR-3 cells that had been transfected with HER-2 cDNA to increase expression to 10(5) receptors/cell, HRG inhibited rather than stimulated growth. Conversely, when HER-2 expression by SKOv3 cells was downregulated by transfection of the viral E1A gene, HRG stimulated rather than inhibited growth. To evaluate the relative importance of HER-3 and HER-4, NIH 3T3 cells were cotransfected with HER-2 and HER-3 or with HER-2 and HER-4. HRG inhibited the growth of cells with a high ratio of HER-2:HER-3, whereas HRG stimulated the growth of cells with low levels of the two receptors. In cells that express only HER-2 and HER-4, HRG stimulated the growth of cells that expressed HER-4 independent of HER-2 levels. Anti-HER-2 antibodies inhibited the growth of transfectants with high levels of HER-2 expression independent of HER-3 or HER-4 expression. In ovarian cancer cells that express all three receptors, the relative levels of HER-2 and HER-3 appear to determine the response to HRG. Taken together, these studies support the concept that the level of HER-2 expression can modulate response to HRG, determining whether the response is stimulatory or inhibitory. In contrast, agonistic antibodies that bind to HER-2 alone inhibit anchorage-independent growth but fail to mimic HRG's ability to stimulate growth of cells with low HER-2: HER-3 ratios.

Antibodies, Monoclonal↗

Reciprocal actions of acupoints on gastrointestinal peristalsis during electroacupuncture in mice.

Orthogonal design was used to observe the gastrointestinal peristalsis in normal and atropine-treated mice after electroacupuncture was applied, singly or in combination, at Neiguan (P 6), Pishu (UB 20) and Zusanli (St 36). The results showed that: 1) electroacupuncture has no significant effect on the gastrointestinal peristalsis in normal mice; 2) Pishu (UB 20) was significantly antagonistic to Zusanli (St 36) in normal mice; 3) the decreased gastrointestinal peristalsis in atropine-treated mice was markedly promoted by electroacupuncture at Zusanli (St 36); and 4) Neiguan (P 6) was significantly antagonistic to Pishu (UB 20) in atropine-treated mice. The results indicated that the reciprocal actions among acupoints should be taken into consideration for point prescription.

Acupuncture Points↗

[Intersection point rule for the retention value with mobile phase composition and boiling point of the homologues and chlorobenzenes in soil leaching column chromatography].

Based on the linear retention equation of the logarithm of the capacity factor (logk') vs. the methanol volume fraction (psi) of aqueous binary mobile phase in soil leaching column chromatography, the intersection point rule for the logk' of homologues and weak polar chlorobenzenes, with psi, as well as with boiling point, has been derived due to existence of the similar interactions among solutes of the same series, stationary phase (soil) and eluent (methanol-water). These rules were testified by experimental data of homologues (n-alkylbenzenes, methylbenzenes) and weak polar chlorobenzenes.

English Abstract↗

[Study on adsorption of atrazine by soil leaching column chromatography].

A recently developed soil leaching column chromatography was applied to study the adsorption of pesticide in water-soil system. Soil was filled directly into a liquid chromatographic column and pesticide solution was applied as an eluant, and the adsorption equilibrium was monitored by a UV detector. The herbicide atrazine, i. e. 2-chloro-4-ethylamino-6-isopropylamino-s-triazine, was chosen as an example. Its mass concentration ranged from 19.73 mg/L to 29.60 g/L. After the soil phase was rinsed with methanol, the amount of atrazine adsorbed was calculated from the difference between the atrazine totally rinsed and that in solution in the column. The low content atrazine sample was determined by enrichment on an ODS column and step-gradient method. It shows that the adsorption of atrazine on a sandy loam soil is in accordance with Freundlich isotherm. The adsorption coefficient Kf is 842.6 mL/kg and the normalized organic carbon adsorption coefficient log Koc is 1.832.

Adsorption↗

[Detection of circulating antigen in serum and cerebrospinal fluid for diagnosis of cerebral cysticercosis].

AIM: To detect circulating antigen(CAg) in serum and cerebrospinal fluid(CSF) from patients with cerebral cysticercosis with specific antiserum by sandwich ELISA. METHODS: Antisera were prepared from rabbits immunized respectively with 3 antigens with molecule weights of 64 kDa, 53 kDa, 32 kDa-30 kDa extracted from Cysticercus cellulosae and purified by SDS-PAGE. RESULTS: When samples from patients were tested with antiserum against 53 kDa antigen, the CAg positive rate was 93.8% in serum and 91.7% in CSF of 32 patients with active cysticercosis, whereas only one positive was found in CSF in 16 patients with inactive cysticercosis. The detection rate of CAg was significantly higher with anti-53 kDa antiserum than with anti-64 kDa and anti-32 kDa-30 kDa antiserum. CONCLUSION: Sandwich-ELISA using antiserum against 53 kDa antigen to detect CAg was found to be a promising assay for diagnosis and evaluation of treatment efficacy of active cerebral cysticercosis in terms of its high sensitivity and specificity.

Animals↗

Molecular cloning of a lobster Gbeta subunit and Gbeta expression in olfactory receptor neuron dendrites and brain neuropil.

We have isolated from the olfactory organ of the American lobster (Homarus americanus) two cDNA clones with homology to beta subunits of G proteins. LobGbeta1 contained a complete open reading frame that predicted an amino acid sequence with >80% identity to Gbeta sequences from other species. LobGbeta2 was a fragment of an open reading frame whose predicted amino acid sequence had 65-69% identity to other Gbeta sequences. LobGbeta2 mRNA was not detectable in the brain, eye plus eyestalk, leg, dactyl, olfactory organ, or tail muscle. In contrast, lobGbeta1 was expressed in all these tissues as a single mRNA species of 6.4 kb and a protein of 37 kD. In the brain and olfactory organ, Gbeta immunoreactivity was almost exclusively confined to neurites: the neuropil regions of the brain and the outer dendrites of the olfactory receptor neurons. Coimmunoprecipitation revealed that lobster Gbeta interacted with both Galpha s and Galpha q. LobGbeta1 is likely to be involved in a wide range of signaling events including olfactory transduction and synaptic transmission in the brain.

Amino Acid Sequence↗

Site-directed mutations in fungal laccase: effect on redox potential, activity and pH profile.

A Myceliophthora thermophila laccase and a Rhizoctonia solani laccase were mutated on a pentapeptide segment believed to be near the type-1 Cu site. The mutation L513F in Myceliophthora laccase and the mutation L470F in Rhizoctonia laccase took place at a position corresponding to the type-1 Cu axial methionine (M517) ligand in Zucchini ascorbate oxidase. The triple mutations V509L,S510E,G511A in Myceliophthora laccase and L466V,E467S,A468G in Rhizoctonia laccase involved a sequence segment whose homologue in ascorbate oxidase is flanked by the M517 and a type-1 Cu-ligating histidine (H512). The single mutation did not yield significant changes in the enzymic properties (including any significant increase in the redox potential of the type-1 Cu). In contrast, the triple mutation resulted in several significant changes. In comparison with the wild type, the Rhizoctonia and Myceliophthora laccase triple mutants had a phenol-oxidase activity whose pH optimum shifted 1 unit lower and higher, respectively. Although the redox potentials were not significantly altered, the Km, kcat and fluoride inhibition of the laccases were greatly changed by the mutations. The observed effects are interpreted as possible mutation-induced structural perturbations on the molecular recognition between the reducing substrate and laccase and on the electron transfer from the substrate to the type-1 Cu centre.

Amino Acid Sequence↗

Ecotropic C-type retrovirus of B16 melanoma and malignant transformation of normal melanocytes.

We reported previously that B16,JB/RH and JB/MS melanomas of C57BL/6 mice express the common melanoma-associated antigen (MAA) recognized by MM2-9B6 monoclonal antibody (MAb). This MAA is encoded by the env gene of an ecotropic MuLV-type retrovirus that somatically emerged in melanomas of C57BL/6 mice. The potential role of this melanoma-associated retrovirus (MelARV) in melanoma formation remains unknown and has not been previously investigated. To test this, normal melanocyte lines (melan-a and C57M) of C57BL/6 mice were infected with the MelARV produced by B16BL6 melanoma. Infection of these melanocytes with the MelARV was associated with the appearance of the MAA recognized by MM2-9B6 MAb. Most of the infected melanocyte sublines were able to grow only in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA). Two infected melanocyte sublines showed morphological changes, were able to grow in the absence of TPA and, after inoculation into C57BL/6 mice, produced rapidly growing, highly pigmented tumors. These new melanomas, derived from the MelARV-infected melan-a and C57M melanocytes, were termed Meli-A1 and Meli-BL, respectively. Southern blot analysis of EcoRI- and HindIII-digested DNAs from these melanomas showed several retroviral insertion sites. One copy of MeIARV was found to be inserted at the end of the 6th leucine domain of the c-maf proto-oncogene, which encodes a basic region/leucine zipper transcription factor related to the AP-1 family that is able to form homodimers or heterodimers with Fos and Jun transcription factors. Our data indicate that c-maf is a common insertion site of MelARV in BL6, Meli-A1 and Meli-BL melanomas, whereas no such insertion site was found in the melanocytes infected with MelARV but not malignantly transformed. Thus, our data imply that the ecotropic MelARV that somatically emerged in B16 and other melanomas of C57BL/6 mice may play a role in malignant transformation.

Animals↗

In vivo Bcl-2 oncogene neuronal expression in the rat spinal cord.

STUDY DESIGN: An acute mechanical rat spinal cord injury model was used to investigate in vivo Bcl-2 oncogene overexpression in neuronal tissue. OBJECTIVES: To introduce the Bcl-2 oncogene in vivo by a recombinant adenovirus vector into rat spinal cord tissue, and to investigate any potential protective effect on neural tissue in the zone of injury in a rat spinal cord model. SUMMARY OF BACKGROUND DATA: The Bcl-2 oncogene inhibits apoptotic and necrotic neural cell death in vitro by regulating an antioxidant pathway at sites of free radical generation. Thus, overexpression of the Bcl-2 oncogene may have a role in limiting the secondary injury cascade of spinal cord injury through its regulation of antioxidants. METHODS: After confirmation of Bcl-2 gene expression in vitro and in vivo in the rat spinal cord, a weight-drop spinal cord injury model was performed on seven rats with prior Bcl-2 inoculation, and on seven rats with prior B-gal inoculation (controls). RESULTS: In vivo Bcl-2 expression was documented by immunostaining. After spinal cord harvest, quantification of percentage preserved tissue at the spinal cord injury site suggested that Bcl-2 overexpression confers neuroprotection. CONCLUSIONS: In vivo Bcl-2 oncogene overexpression was successfully induced in neuronal tissue. After Bcl-2 oncogene expression in the rat spinal cord, the zone of microscopic injury was diminished. Further investigation of the Bcl-2 oncogene for potentially enhancing neuronal survival after spinal cord injury appears indicated.

Adenoviridae↗

BCL-X expression in multiple myeloma: possible indicator of chemoresistance.

Because murine myeloma plasma cells and normal human lymph node plasma cells express BCL-X, we evaluated BCL-X expression in malignant human plasma cells. BCL-X expression was detected in several human myeloma cell lines, as well as in CD38-sorted bone marrow cells obtained from some patients. Only the antiapoptotic long form of BCL-X (BCL-X-L), was detected. Because BCL-X-L expression can protect tumor cells from apoptotic death induced by chemotherapeutic agents, we tested the clinical relevance of expression in 55 archival bone marrow biopsies. The biopsies were stained by immunohistochemistry, and BCL-X expression was correlated with the subsequent response to treatment. BCL-X expression in malignant plasma cells strongly correlated with decreased response rates in patient groups treated with either melphalan and prednisone or vincristine, Adriamycin, and dexamethasone. Response rates were 83-87% in non-BCL-X-expressing cases and 20-31% in BCL-X-expressing cases. In addition, BCL-X expression was more frequent in specimens taken from patients at relapse (77%), when compared to those at initial diagnosis (29%). Further support for the association of drug resistance with BCL-X-L expression came from studies of the 8226 dox-40 cell line. This line, which expresses p-glycoprotein and serves as a model of multidrug resistance in multiple myeloma cells, demonstrated an up-regulated expression of BCL-X-L, which was relatively specific, in that BCL-2 or BAX expression was not altered. In addition, dox-40 cells demonstrated a generalized resistance to apoptosis that was induced by several different agents. These results indicate that malignant plasma cells can express BCL-X-L and that such expression may be a marker of chemoresistant disease.

Antineoplastic Combined Chemotherapy Protocols↗

Evidence of shallow fault zone strengthening after the 1992 M7.5 landers, california, earthquake

Repeated seismic surveys of the Landers, California, fault zone that ruptured in the magnitude (M) 7.5 earthquake of 1992 reveal an increase in seismic velocity with time. P, S, and fault zone trapped waves were excited by near-surface explosions in two locations in 1994 and 1996, and were recorded on two linear, three-component seismic arrays deployed across the Johnson Valley fault trace. The travel times of P and S waves for identical shot-receiver pairs decreased by 0.5 to 1.5 percent from 1994 to 1996, with the larger changes at stations located within the fault zone. These observations indicate that the shallow Johnson Valley fault is strengthening after the main shock, most likely because of closure of cracks that were opened by the 1992 earthquake. The increase in velocity is consistent with the prevalence of dry over wet cracks and with a reduction in the apparent crack density near the fault zone by approximately 1.0 percent from 1994 to 1996.

Journal Article↗

Expression of p16 induces transcriptional downregulation of the RB gene.

The RB and p16(INK4A) tumor suppressor genes function in the same pathway of cell cycle control. Previous evidence indicates that the p16(INK4A) gene is transcriptionally repressed by the RB gene product, pRB. In this study using human ovarian cancer cell lines, we found that RB protein and mRNA were expressed at higher levels in cell lines lacking p16 than in those with normal p16. Since this suggests a potential role of p16 in regulating the cellular level of pRB, we studied the effect of wild-type p16(INK4A) on expression of the RB gene. Introduction of p16(INK4A), carried by an adenovirus vector, into p16-negative cell lines dramatically decreased expression of RB protein and mRNA. Nuclei run-off assays demonstrated that p16 expression induced transcriptional downregulation of the RB gene. These results indicate that expression of RB is inversely regulated by p16. The findings reveal a new dimension of pRB-p16 interaction and should have implications for p16(INK4A)-mediated gene therapy.

Adenoviridae↗