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Biomedical subjects

S Fu

Publications and source records attributed to S Fu.

At least 19 recordsLinked to original sources

Kavalactones fail to inhibit alcohol dehydrogenase in vitro.

In recent years, Kava kava (Piper methysticum, Forst. f., Piperaceae), a folkloric beverage and popular herbal remedy, has been implicated in a number of liver failure cases. Many hypotheses as to the mechanism of its hepatotoxicity, for example interactions with other co-ingested medication, have been postulated. This present study investigated whether pharmacokinetic interactions between kava constituents and alcohol via alcohol dehydrogenase (ADH) inhibition by individual kavalactones might explain its claimed hepatotoxic effects. Four kavalactones, (+/-)-kavain, methysticin, yangonin and desmethoxyyangonin, fail to inhibit ADH in vitro at 1, 10 or 100 microM concentrations.

Alcohol Dehydrogenase↗

Proteomic analysis of childhood leukemia.

Childhood acute lymphoblastic and myeloid leukemias are stratified into molecular and cytogenetic subgroups important for prognosis and therapy. Studies have shown that gene expression profiles can discriminate between leukemia subtypes. Thus, proteome analysis similarly holds the potential for characterizing different subtypes of childhood leukemia. We used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze cell lysates from childhood leukemia cell lines as well as pretreatment leukemic bone marrow derived from childhood leukemia cases. Comparison of the acute myeloid leukemia (AML) cell line, Kasumi, and the biphenotypic myelomonocytic cell line, MV4;11, with the acute lymphoblastic leukemia (ALL) cell lines, 697 and REH, revealed many differentially expressed proteins. In particular, one 8.3 kDa protein has been identified as a C-terminal truncated ubiquitin. Analysis of childhood leukemia bone marrow showed differentially expressed proteins between AML and ALL, including a similar peak at 8.3 kDa, as well as several proteins that differentiate between the ALL t(12;21) and hyperdiploid subtypes. These results demonstrate the potential for proteome analysis to distinguish between various forms of childhood leukemia. Future analyses are warranted to validate these findings and to investigate the role of the C-terminal truncated ubiquitin in the etiology of ALL.

Acute Disease↗

Towards understanding language organisation in the brain using fMRI.

Functional magnetic resonance imaging (fMRI), which allows non-invasive mapping of human cognitive functions, has become an important tool for understanding language function. An understanding of component processes and sources of noise in the images is contributing to increased confidence in the reproductability of studies. This allows clinical applications, e.g., for pre-surgical lateralisation of language functions in patients with temporal lobe epilepsy. fMRI is a sensitive method for mapping regions involved in language functions. We recently have applied it to study the effect of word surface form on reading with a comparison of responses to Chinese characters or alphabetical Pinyin. Interpretation of fMRI activations must be made with caution; fMRI suggests task-associated activation, but does not independently confirm that such activity is necessary. However, complementary studies can be performed using transcranial magnetic stimulation (TMS), which can be used to interfere with brain activity in a specific region transiently for characterisation of the behavioural effects. We describe how TMS combined with fMRI has confirmed a role for the left inferior frontal cortex in semantic processing.

Asian People↗

A Controllable and Observable Protein Cystallization Facility.

A Controllable and Observable Protein Crystallization Facility (ACOP) was developed in 1999 for space experiment in the Get Away Special canister of Space Shuttle. To regulate the vapor diffusion rate, in a crystallization chamber, five cells each containing precipitant solution of different concentrations, exposed to one protein cell in turn. Five layers of chambers were overlapped coaxially. The crystallization process was observed and recorded by digital cameras. Structure of facility and result of image sequence were given.

Crystallization↗

Distinct functions of two isoforms of a homeobox gene, BP1 and DLX7, in the regulation of the beta-globin gene.

Homeotic proteins are transcription factors that regulate the expression of multiple genes involved in development and differentiation. We previously isolated a cDNA encoding such a protein from the human leukemia cell line K562, termed Beta Protein 1 (BP1), which is involved in negative regulation of the human beta-globin gene. Sequence comparison revealed that BP1 is a member of the distal-less (DLX) family of homeobox genes and that it shares its homeodomain and 3' sequences with another DLX cDNA, DLX7. BP1 and DLX7 exhibit unique 5' regions, diverging at nucleotide 565 of BP1. We mapped this new distal-less family member BP1 to chromosome 17q21-22 by FISH and PCR, which is the same locus to which DLX7 has been mapped. These results strongly suggest that BP1 and DLX7 are isoforms (derived from the same gene). Since our previous data demonstrated that BP1 and DLX7 are frequently co-expressed, we determined whether DLX7 is also involved in the negative regulation of the beta-globin gene. Mobility shift assays demonstrated that both BP1 and DLX7 proteins, synthesized in vitro, bind to the same BP1 binding site. However, using transient assays, we showed that although BP1 represses activity of a reporter gene through either of two silencer DNA sequences upstream of the beta-globin gene, DLX7 did not show repressor activity against the beta-globin promoter. Further characterization of these apparent isoforms is of significance since they are jointly expressed in acute myeloid leukemia and in many leukemia cell lines.

Base Sequence↗

Identification of TNF-alpha-sensitive sites in HCMVie1 promoter.

Viral vectors using the human cytomegalovirus immediate-early promoter (HCMVie1 promoter) are potentially efficient tools for gene delivery in vivo to diverse cell types. We previously demonstrated that two cytokines, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (INF-gamma), inhibited transgene expression from this promoter in skeletal and cardiac myocytes. In this study, electrophoretic mobility shift assays (EMSAs) were performed to identify the TNF-alpha response elements from the HCMVie1 promoter. The results show that TNF-alpha enhances the interaction of nuclear proteins from the C2C12 myocyte line with a single restricted segment of the HCMVie1 promoter. In vitro DNase I footprinting defined precisely the sites of interaction to two elements: nucleotides -1 to 0 and +24 to +36 relative to a transcription initiation cap homologous in the HCMVie1 promoter. These sites contain homologous sequences for cap initiation site (82%) and NFkappaB (62%) sites, respectively. Specificity was further ascertained by competitive EMSAs with wild-type and mutant oligonucleotide probes. Southwestern blotting showed that three proteins (45, 30, and 20 kDa) bound to this TNF-alpha-sensitive element, separately. However, EMSAs failed to prove a role for Yin Yang-1 (YY-1), NFkappaB (p65), or NFkappaB (p50) in binding to these sites. Our results provide evidence for two novel sites in the HCMVie1 promoter that are targets for TNF-alpha enhanced binding of transcription factors.

Antigens, Viral↗

The attentional effects of peripheral cueing as revealed by two event-related potential studies.

OBJECTIVE: The mechanism of visual spatial attention elicited by peripheral cueing was investigated in two studies. METHOD: Event-related potentials (ERPs) were recorded when the subjects were performing a spatial frequency discrimination task and a location discrimination task. Stimuli were randomly flashed in the left or right visual field. Prior to each stimulus a peripheral cue was presented with a validity of 75%. RESULTS: The subjects responded faster to valid trials than to invalid trials. The earliest visual ERP component, C1, was not modulated by the cue validity, suggesting that visual spatial attention elicited by peripheral cueing does not involve striate cortex. Valid trials elicited larger contralateral P1 but a smaller contralateral N1 than invalid trials. The early onsets of these attentional effects show that spatial attention affects stimulus processing at early sensory/perceptual stages. The latencies of contralateral P1 and contralateral N1 were shorter for invalid trials, however. The ipsilateral N1 was enhanced by valid trials in the spatial frequency discrimination task but was not in the location discrimination task, whereas the contralateral N1 was larger for invalid trials than for valid trials in both tasks. CONCLUSION: The results indicate that involuntary allocation of attention involves different mechanisms from voluntary allocation of attention.

Adult↗

[Expression of tumor suppressor genes p16, p21 and p53 in a pair of lung adenocarcinoma cell lines with different metastasis potentials: Anip973 and AGZY83-a].

OBJECTIVE: In order to investigate the suppression effect of tumor suppressor genes in lung adenocarcinoma. METHODS: p16 and p21 expression vectors were transfected into a pair of lung adenocarcinoma cell lines with different metastasis potentials: Anip973(high metastasis potential)and AGZY83-a (low metastasis potential). In the mean time, AGZY83-a, Anip973, AGZY83-ap16 and Anip973p16 were infected with recombinant adenovirus encoding wild- type p53 gene. The suppression effects of these genes were evaluated by cell growth curve, MTT, cloning efficiency assay, flow cytometric analysis and TUNEL technique. RESULTS: Overexpression of p16 gene in Anip973 and AGZY83-a could only lengthen the G(1) phase while increased expression of p21 in both of the cell lines was associated with significant lengthening of G(1) phase, decreased proliferation potential and decreased cloning efficiency. High efficient expression of wild-type p53 gene in AGZY83-a, Anip973, Anip973p16 and AGZY83-ap16 inhibited the growth of these four kinds of lung cancer cells and killed the cells in the end. Apoptosis was detected in all the four kinds of cells. The suppression effect of p53 gene was higher in Anip973 and Anip973p16 than in AGZY83-a and AGZY83-ap16 while co-expression of p53 and p16 in this pair of cell lines inhibited the cells more efficiently as compared with the expression of p53 gene. CONCLUSION: Increased expression of p21 gene suppressed the lung adenocarcinoma cells by G(1) arrest and the co-transfection of tumor suppressor genes p16 and p53 into the lung adenocarcinoma cell line proved more effective in lung cancer gene therapy.

Adenocarcinoma↗

[Application of chromosome painting technique to analysis of structural aberration of human chromosomes].

OBJECTIVE: This study was aimed at using chromosome painting technique to detect translocation, especially microtranslocations, on chromosomes in comparison with G-banding analysis. METHODS: Chromosome painting technique was applied to analysis of metaphase chromosomes of patients for detecting translocations with biotin-labeled chromosomes X, Y, 14q, 10 specific probes. RESULTS: Fluorescence in situ hybridization FISH signals were shown clearly in slides even in specimen stored at room temperature for 10 years and at -80 centigrade degree. Translocations were located precisely. CONCLUSION: Microtranslocations, which are hard to analyze by G-banding, can be detected exactly using chromosome painting technique with G-band karyotype on metaphase chromosome.

Adult↗

[Analysis of loss of heterozygosity on 19p in primary gastric cancer].

OBJECTIVE: To investigate the loss of heterozygosity (LOH) frequency of microsatellite loci in primary gastric cancer samples and locate the deleted regions on 19p in which might exist human gastric cancer related genes. METHODS: The LOH of microsatellite loci on chromosome 19p was analyzed using PCR-SSLP-silver stain method in 43 primary gastric cancers and their paired normal tissues. RESULTS: In 43 primary gastric tumors, LOH was detected on the site for D19S424(29.63%), D19S216(11.53%), D19S406 (33.33%), D19S413(8.57%), D19S221(13.15%), D19S226(8.00%), D19S411(6.45%), D19S883(6.89%), and D19S886(10.71%), microsatellite instability (MSI) was found at the same time at locus D19S886 (17.85%). CONCLUSION: The most common LOH occurrence at D19S406 and D19S424 might imply the existence of the potential genes related to the tumorigenesis of gastric cancer in these loci.

Chromosome Mapping↗

Treatment of hepatic failure with artificial liver support system.

OBJECTIVE: To assess the effectiveness of artificial liver support system (ALSS) treatment in patients with hepatic failure. METHODS: 235 cases of hepatic failure were treated with ALSS in our hospital. All data were analyzed by SPSS. The effectiveness of ALSS treatment was compared according to different stages (i.e., early, middle and end stages). RESULTS: 108 patients survived after therapy of ALSS. After each ALSS treatment, the liver function of these patients was greatly improved, the serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while the ratio of branched chain amino acids and aromatic amino acids (BCAA/AAA ratio) increased; patients treated with ALSS in the early or middle stages of disease had much higher survival rates than patients in the end stage of disease. CONCLUSION: ALSS is a reliable therapy for advanced liver diseases and treatment at early or middle stages is appropriate.

Adult↗

Sensitization of prostate cancer cell lines to 5-fluorocytosine induced by adenoviral vector carrying a CD transcription unit.

OBJECTIVE: To investigate the efficiency of the cytosine deaminase adenoviral/5-fluorocytosine system on prostate cancer cell lines. METHODS: We used cell culture, infectivity and sensitivity tests, to observe bystander effect by animal tests. RESULTS: Established prostate cancer cell lines are eventually infectible by adenoviral vector. The ratio of vector/cell at which infection occurs depends on the specific cell line. The peak of expression of the transferred cytosine deaminase gene occurred in cells at different time, but persisted beyond 11 days. These prostate cell lines are sensitized to 5-fluorocytosine by infection with adenoviral vector carrying the cytosine deaminase gene. Only 5% of the LNCap and 10% of the RM-1 cells were infected and produced 100% cell death. In the animal test, there was significant inhibition of tumor growth at a ratio of 400 vector particles/cell with the systematic treatment of 5-fluorocytosine. CONCLUSIONS: Adenoviral vector carrying a cytosine deaminase transcription unit can sensitize prostate cancer cell lines to 5-fluorocytosine. The system can significantly inhibit the growth of prostatic tumors in mice.

Adenoviridae↗

Investigation of infection risk and the value of urine endotoxin during extracorporeal shock wave lithotripsy.

OBJECTIVE: To clarify the infection risks and the value of endotoxin determination in urine during extracorporeal shock wave lithotripsy (ESWL). METHODS: According to the distribution and complications of upper urinary calculi, 164 patients were divided into five groups. Group A consisted of 48 patients with 1 to 4 renal calculi, which were or less than 2 cm in diameter. Group B was composed of 24 patients with renal calculus larger than 2 cm in diameter or one to multiple renal calculi. Group C was composed of 22 patients with 1 to 3 renal calculi accompanied by 1 to 2 ureteric calculi. Group D consisted of 51 patients with 1 to 3 ureteric calculi that were 0.5 to 1.2 cm in diameter, respectively. Group E included 19 patients with complicated renal calculus, such as casting and staghorn renal calculus. Urine and blood samples of these patients were obtained before and after ESWL, respectively. Their urine samples were proven sterile prior to treatment. All samples were cultured for bacteria and investigated for endotoxin concentration by the limulus lysate test. RESULTS: No significant difference in serum endotoxin was noted before and after ESWL. Blood bacterial cultures were all negative in all patients after ESWL, similar to those before ESWL. Significant increases in urine endotoxin after ESWL compared with that before ESWL in patients of Groups B, C and E were observed, respectively (P < 0.05). There was no significant difference in urine endotoxin after ESWL compared with that before ESWL in patients of Groups A and D. The positive incidences of urine bacterial culture were significantly increased (P < 0.05) in Groups B and C and very significantly increased (P < 0.01) in Group E compared with those in Groups A and D. CONCLUSIONS: Urinary infection risk following ESWL was lower in patients with one to several renal calculi, which were less than 2 cm in diameter and did not interfere obviously with the urine flow or in patients with 1 to 3 ureteric calculi that were 0.5 to 1.2 cm in diameter. The risk was higher in those with complicated calculi, such as casting, staghorn renal calculus, renal calculus larger than 2 cm in diameter or renal calculi accompanied by ureteric calculi. For patients with higher infection risk after ESWL, prophylactic antibiotics are necessary even if bacteriuria is not present before ESWL. Endotoxin determination in urine is a reliable, sensitive and simple method for the diagnosis of bacterial infection in patients undergoing ESWL.

Adolescent↗

[Correlation of cell apoptosis induction with expression of human beta5 integrin on hematopoietic cells].

OBJECTIVE: To investigate the function of alpha(v)beta5 integrin in hematopoietic cells. METHODS: Beta5 integrin cDNA was expressed in K562 cells through a retroviral vector system. The changes of the alpha(v)beta5 and alpha(v)beta3 integrins expression in apoptosis and differentiation induced by serum depletion were observed. RESULT: The beta5 integrin cDNA failed to express in K562 cells after the introduction of the beta5 integrin retrovirus vector pG beta5CHT. Imbalanced expression of alpha(v)beta3 and alpha(v)beta5 integrins occurred during apoptosis and differentiation induced by serum depletion. Treatment of hematopoietic cells with anti-alpha(v)beta5 monoclonal antibody inhibited the cells apoptosis. CONCLUSION: Overexpression of the alpha(v)beta5 integrin cDNA in hematopoietic cells was associated with the inhibition of cell proliferation and apoptosis.

Apoptosis↗