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Biomedical subjects

W Fu

Publications and source records attributed to W Fu.

At least 19 recordsLinked to original sources
PubMed2003

The vertical distribution and diversity of marine bacteriophage at a station off Southern California.

Sixty-two bacteriophages were isolated on eight indigenous bacteria from a Pacific Ocean station spanning 887-m vertical depth, on two occasions between 1999 and 2000. On the basis of 16S rRNA sequences, six hosts were tentatively identified to be in the genus Vibrio and the other two were closely related to Altermonas macleodii (W9a) and Pseudoalteromonas spp. (W13a). Restriction fragment length polymorphism (RFLP) analysis of phage genomes using AccI and HapI showed that 16 phages infecting host C4a (Vibrio) displayed 14 unique RFLP patterns. However, identical phages infecting host C4b, C6a, and C6b (all Vibrio) were obtained from both the surface layer and the hypoxic zone at 850 m. Most phage isolates from the second year had a different RFLP pattern but shared genetic similarity to the phages infecting the same host from the previous year based on a hybridization study using phage genome probes. Cluster analysis of RFLP patterns and hybridization results also indicated that phages infecting the same or genetically related hosts, in general, shared higher degrees of homology in spite of the diverse RFLP patterns. Pulsed field gel electrophoresis (PFGE) analysis of native viral genomes indicated a range in genome size from less than 40 to 200 kb, and the dominant band shifted up by about 5-10 kb in the deep samples compared to the shallow ones. Hybridization of phage genome probes with total viral community DNA from various depths suggests these isolates, or at least some of their genes, represent a detectable portion of the natural viral community and were distributed throughout the water column. Thus, the results of this study demonstrated that the genetic diversity of bacteriophage in the ocean is far greater than that of their bacterial hosts. However, host range may have contributed to the evolution of the diverse phage population in the marine environment.

Bacteriophages↗
PubMed2001

Telomerase protects developing neurons against DNA damage-induced cell death.

In mitotic cells, telomerase adds repeats of a DNA sequence (TTAGGG) to the ends of chromosomes (telomeres) thereby maintaining their length and preventing cellular senescence. We recently reported that the catalytic subunit of telomerase (TERT) is expressed in neuronal progenitor cells and in early postmitotic neurons in the developing rodent brain. We now report that TERT can protect cultured PC12 cells and embryonic hippocampal neurons against death induced by DNA damage. Overexpression of TERT in PC12 cells increases their resistance to the topoisomerase inhibitors camptothecin and etoposide. Hippocampal neurons in which TERT levels are decreased using antisense technology exhibit increased vulnerability to the DNA-damaging agents. Emerging findings suggest that DNA damage may trigger the death of neurons during brain development and in neurodegenerative disorders. Our data therefore suggest roles for TERT in modulating such cell deaths.

Animals↗
PubMed2001

Regulation of the cycling of timeless (tim) RNA.

Circadian rhythms in Drosophila depend upon expression of the timeless (tim) and period (per) genes, which encode interacting components of the endogenous clock. These two clock genes show a robust circadian oscillation in transcription rate as well as RNA and protein levels. Transcriptional activation of both genes requires the basic helix-loop-helix (bHLH) PAS transcription factors dCLOCK (dCLK) and CYCLE (CYC), which bind E-box elements. We investigated the role of E-box elements in regulating behavioral rhythmicity and tim gene expression. We show that mutation of the upstream E-box in the tim gene prevents the rescue by tim cDNA sequences of the arrhythmic tim(01) phenotype. RNA encoded by this mutated tim transgene fails to cycle and is expressed at low levels. While a tim transgene carrying a wild-type E-box restores behavioral rhythms, tim RNA levels are intermediate to those of the mutant E-box transgenic lines and wild type, and do not display high amplitude cycling. On the other hand, high-amplitude RNA cycling was consistently obtained with a tim transgene that contains genomic, rather than cDNA, sequences. To identify additional sequences that may be required for tim cycling, we investigated the role of an E-box in the first intron of the tim gene through cell culture experiments. In these experiments, the presence of this intron did not have any effect on the activation of tim transcription by dCLK/CYC. As the upstream E-box was implicated in activation by dCLK/CYC in cell culture, we assayed sequences containing this E-box for association with proteins in fly head extracts. These studies provide the first biochemical evidence for an in vivo complex containing dCLK and CYC that binds the tim upstream sequence and is detected at all times of day. Together, these data highlight molecular mechanisms that are critical for behavioral rhythms.

ARNTL Transcription Factors↗
PubMed2001

Emerging roles for telomerase in regulating cell differentiation and survival: a neuroscientist's perspective.

Telomerase is a reverse transcriptase that adds repeats of a DNA sequence (TTAGGG) to the ends of chromosomes (telomeres) in mitotic cells, thus maintaining their length and preventing cell cycle arrest and cell death (cellular senescence). During development of the nervous system, telomerase activity levels are high in neural progenitor cells, but then they decrease as cells differentiate or die. The catalytic subunit of telomerase (TERT) remains at relatively high levels during the process of neuronal differentiation and then decreases sharply during the period when synapses form and programmed cell death occurs. TERT promotes survival of developing brain neurons. Suppression of telomerase activity and TERT expression promotes apoptosis of neurons, whereas overexpression of TERT prevents apoptosis by suppressing cell death at a premitochondrial step in the death cascade TERT may suppress DNA damage and/or apoptotic signals activated by damaged DNA. Recent studies of the transcriptional regulation of the TERT gene suggest that this enzyme may mediate the cell survival-promoting actions of diverse signals including estrogen, cytokines and neurotrophic factors. The elucidation of the functions of telomerase activity and TERT in neuronal differentiation and survival may lead to novel approaches for preventing neuronal death and promoting recovery of function in various neurodegenerative conditions.

Animals↗
PubMed2001

Chaoslike behavior in nonchaotic systems at finite computation precision.

The dynamical behavior of a two-dimensional map is investigated numerically. A chaoslike behavior, i.e., a nonsmooth distribution of the attractor and seemly sensitive dependence of the motion on initial condition is found as the system state is nonchaotic (both Lyapunov exponents are nonpositive). The key point for this strange behavior is that the mode corresponding to the second negative Lyapunov exponent contains positive local Lyapunov exponent segments. It is argued that this kind of behavior may be typical and easily observed in practical numerical computations and experiments where small noise is inevitable.

Journal Article↗
PubMed2001

Discovery of new DNA amplification loci in prostate cancer by comparative genomic hybridization.

BACKGROUND: DNA sequence amplifications are involved in the progression of many tumor types, and have also been found in advanced prostate cancer. The aim of this study was to detect new loci of DNA amplifications in prostate cancer. METHODS: Comparative genomic hybridization (CGH) was used for whole genome screening of DNA sequence copy number alterations in 27 advanced prostate cancers. RESULTS: The most prevalent changes were losses of 8p, 13q (52%, each), 6q (48%), 18q (37%), 5q (30%), 2q, 4q and 16q (26%, each), and gains of 8q (48%), Xq (40%), and Xp (26%). In addition, 16 high-level amplifications were found. These included Xq12 (five), 8q24 (two), and 11q13 (one) with known putative target genes (androgen receptor, MYC and Cyclin D1), and 1q21-25 (three), 10q22 (two), 17q23-24 (two), and 8q21 (one) where the target genes remain unknown. CONCLUSIONS: High-level amplifications at different chromosomal sites occur in advanced prostate cancer. The detection of amplified chromosomal regions may serve as a starting point to discover novel oncogenes involved in prostate cancer progression.

Aged↗
PubMed2001

Molecular markers in Paget disease of the breast.

BACKGROUND AND OBJECTIVES: Molecular markers are increasingly being analyzed in tumor specimens because of their relevance to both prognosis and choice of therapy. Paget disease of the breast is an uncommon form of breast cancer, in which molecular markers have not been well characterized. The objective of this study was to investigate the expression of c-erbB-2, p53, Ki-67, Cyclin D1, Bcl-2, estrogen receptors (ER), and progesterone receptors (PR) in mammary Paget disease. METHODS: Archival tumor tissues from 14 patients diagnosed between 1990 and 1999 with Paget disease of the breast were analyzed for these molecular markers by using an automated immunohistochemical assay. Both the intraepidermal Paget cells and the underlying carcinoma were assessed for these markers. RESULTS: The majority of Paget cells were positive for c-erbB-2 (92.9%), Cyclin D1 (100%), and Ki-67 (85.7%), but very few were positive for Bcl-2 (14.3%). p53 was overexpressed in 42.9% of the cases, and only 28.6% were positive for ER and PR. The rate of expression of these biologic markers was similar in both the Paget cells and the underlying intraductal and/or ductal carcinoma cells. CONCLUSIONS: Tumors from patients with Paget disease of the breast were positive for c-erbB-2, Cyclin D1, and Ki-67, molecular markers commonly associated with more aggressive tumor behavior and poorer survival in breast cancer patients. Few of these tumors expressed Bcl-2 or ER and PR, which are generally associated with a better prognosis. Similar expression of these markers in both Paget cells and the underlying carcinoma supports the theory that these cells are the result of an intraepidermal spread of ductal carcinoma.

Biomarkers, Tumor↗
PubMed2001

Caspase-mediated suppression of glutamate (AMPA) receptor channel activity in hippocampal neurons in response to DNA damage promotes apoptosis and prevents necrosis: implications for neurological side effects of cancer therapy and neurodegenerative disorders.

DNA damage in neurons is implicated in the pathogenesis of several neurodegenerative disorders and may also contribute to the often severe neurological complications in cancer patients treated with chemotherapeutic agents. DNA damage can trigger apoptosis, a form of controlled cell death that involves activation of cysteine proteases called caspases. The excitatory neurotransmitter glutamate plays central roles in the activation of neurons and in processes such as learning and memory, but overactivation of ionotropic glutamate receptors can induce either apoptosis or necrosis. Glutamate receptors of the AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate) type mediate such physiological and pathological processes in most neurons. We now report that DNA damage can alter glutamate receptor channel activity by a mechanism involving activation of caspases. Whole-cell patch clamp analyses revealed a marked decrease in AMPA-induced currents after exposure of neurons to camptothecin, a topoisomerase inhibitor that induces DNA damage; N-methyl-d-aspartate (NMDA)-induced currents were unaffected by camptothecin. The decrease in AMPA-induced current was accompanied by a decreased calcium response to AMPA. Pharmacological inhibition of caspases abolished the effects of camptothecin on AMPA-induced current and calcium responses, and promoted excitotoxic necrosis. Combined treatment with glutamate receptor antagonists and a caspase inhibitor prevented camptothecin-induced neuronal death. Caspase-mediated suppression of AMPA currents may allow neurons with damaged DNA to withdraw their participation in excitatory circuits and undergo apoptosis, thereby avoiding widespread necrosis. These findings have important implications for treatment of patients with cancer and neurodegenerative disorders.

Animals↗
PubMed2001

CDKNA2A mutation analysis, protein expression, and deletion mapping of chromosome 9p in conventional clear-cell renal carcinomas: evidence for a second tumor suppressor gene proximal to CDKN2A.

Inactivation of tumor suppressor genes on chromosome 9p is considered a critical event in renal cell carcinoma pathogenesis. Alterations of CDKN2A on 9p21 have been reported in renal cancer cell lines, but their relevance for primary renal carcinomas is unclear. Loss of heterozygosity (LOH) was analyzed by using four polymorphic microsatellites at D9S970 (9p12-9p13), D9S171 (9p13), D9S1748 (9p21), and D9S156 (9p21) in 113 primary conventional clear-cell renal cell carcinomas (CRCCs). Allelic deletion was detected in 21 of 88 informative CRCCs (24%) with the highest rate of LOH being observed at D9S171 on 9p13 (20%). Chromosome 9p LOH was associated with short tumor-specific survival in stage pT3 RCC (P = 0.01). Fluorescence in situ hybridization analysis of 54 CRCCs revealed no homozygous CDKN2A deletions indicating that this mechanism of CDKN2A inactivation is rare in CRCC. Sequencing of 113 CRCCs showed that 13 tumors (12%) had a 24-bp deletion abrogating codons 4 through 11 of CDKN2A. Immunohistochemical CDKN2A expression was absent in normal renal tissue and was only detected in six of 382 CRCCs (1.5%) on a renal tumor microarray. These data suggest that CDKN2A alterations are present in a small subset of CRCCs and a second, yet unknown tumor suppressor gene proximal to the CDKN2A locus, may play a role in CRCC development.

Adenocarcinoma, Clear Cell↗
PubMed2001

Macrolides: structures and microbial targets.

The macrolide class of antibiotics is well established and often recommended for use in the treatment of community-acquired respiratory tract infections. A number of agents with varying antimicrobial activity have been developed via chemical modification of the core macrolide structure, a macrocyclic lactam ring. Although structurally diverse, the macrolides share a common ability to bind to the bacterial 50S ribosome subunit and inhibit protein synthesis, thereby preventing bacterial multiplication. Resistance in the clinic is due to modification of the 50S subunit in the area of the peptidyl transferase center or to an efflux pump. The newer macrolides, and in particular azithromycin, with their broad-spectrum microbiological profile have extended the therapeutic uses of this class of antibiotics and ensured that they remain an integral part of the clinician's armamentarium.

Anti-Bacterial Agents↗
PubMed2001

Paget disease of the breast: analysis of 41 patients.

The treatment for the patients with Paget disease of the breast is controversial. This review of its natural history, treatment approach, and clinical outcome will help to formulate treatment. Forty-one patients with a diagnosis of Paget disease of the breast were retrospectively reviewed at Providence Hospital & Medical Centers from 1980 to 1999. Ninety-eight percent of patients had underlying carcinoma (ductal carcinoma in situ and/or invasive ductal cancer). Patients with a palpable mass have a much higher incidence of invasive ductal cancer, positive lymph node, and a worse survival rate. The median length of follow-up was 42 months (range: 6--200 months). Twenty-seven percent of patients (11/41) had conservative operations, including 1 patient with a palpable mass; 10 patients with no palpable mass; and 3 patients with recurrence after conservative operation. Thirty-seven percent of patients received adjuvant therapy. Paget disease of the breast has very high incidence of underlying carcinoma (100% in a palpable mass, 96% in nonpalpable mass). Patients with a palpable mass have a worse survival than do patients with nonpalpable mass. Conservative operation should cautiously be selected even for patients with no palpable mass because of a higher recurrence rate.

Adult↗
PubMed2001

[Effect of estrogen on hemodynamics and vascular remodeling with Takayasu arteritis].

This study utilized Takayasu arteritis (TA) model to do the experiment in order to observe the remodeling of arterial geometry. Plasma estrogen, progesterone and products of nitrous oxide (NO2- and NO3-) were examined. Qualitative analyses of maximum (MAX), minimum (MIN) and mean (MEAN) velocity of blood flow, resistant index (PI), pulsatile index (PI), and shear stress (SS) of abdominal aorta were performed. The results showed that plasma estrogen, progesterone and products of nitrous oxide were respectively 1137.80 +/- 189.30 pg.ml-1, 14.10 +/- 1.61 micrograms.ml-1 and 195.78 +/- 53.01 mumol.L-1 in experiment group, whereas in control group, they were 34.74 +/- 10.20 pg.ml-1, 2.60 +/- 1.83 micrograms.ml-1 and 12.16 +/- 3.28 mumol.L-1 respectively, P < 0.01. In comparison of hemodynamic parameters of abdominal aorta, the MAX and MIN of experiment group were profoundly higher than those of control group. SS increased markedly in experiment group. The observation of arterial remodeling in vitro found wall thickening. The thickness of abdominal aortic wall and inside diameter of vessel cavity ratio (h/Di) was 0.6145 +/- 0.1654 in experiment group and 0.2151 +/- 0.0266 in control group, P < 0.01. The arterial collagen content in experimental group was significantly higher than that in control group. Hyperestrinemia gives rise to a series of hemodynamic alterations, influences vessel remodeling along with TA, and finally results in arterial stenosis, occlusion or aneurysms due to the constitutional composition of vascular wall reforming.

Animals↗
PubMed2001

[Arousals from sleep in patients with obstructive disordered breathing: a comparison study for mechanisms].

OBJECTIVE: To explore the stimuli triggering respiratory arousal. METHODS: Twenty-five patients with excessive daytime sleepiness (EDS) were monitored by nocturnal polysomonography (PSG) and respiratory inductive plethysmography. Patients with obstructive apnea/hypopnea index (AHI) >/= 5/h were diagnosed as obstructive sleep apnea syndrome (OSAS). Patients with Epworth Sleepiness Score >/= 12, frequent inspiratory flow limitation related arousal during sleep and AHI < 5/h were diagnosed as upper airway resistance syndrome (UARS). Seven normal subjects were recruited as controls. RESULTS: Patients with OSAS: AHI (32.8 +/- 19.1)/h, percentage of time spend when oxygen saturation lower than 90% (SLT90%) (11.3 +/- 16.5)%, arousal index (ArI) (35 +/- 17)/h, n = 15. Patients with UARS: AHI (2.5 +/- 1.4)/h, SLT90% (0.1 +/- 0.1)%, ArI (30 +/- 16)/h, n = 10. Normal subjects: AHI (5.9 +/- 4.4)/h, SLT90% (0.2 +/- 0.4)%, ArI (13 +/- 5)/h, n = 7. Though the levels of AHI and SLT90% in patients with UARS were similar to those in normal subjects (H = 2.92, P = 0.87 or H = 0.086, P = 0.77), much lower than those in OSAS patients (H = 12.3, P = 0.000 5 and H = 6.64, P = 0.01), ArI in UARS was just as high as that in OSAS (H = 0.49, P = 0.48). CONCLUSION: Arousals from sleep in patients with obstructive sleep disordered breathing might be mainly caused by inspiratory flow limitation rather than by episodic apnea or desaturation.

Adult↗
PubMed2001

[Study on structure change and hypermethylation of p16 gene in multiple myeloma].

OBJECTIVE: To illustrate the role of structure and hypermethylation of p16 gene in the pathogenesis of multiple myeloma(MM). METHODS: By using PCR-single strand conformation polymorphisms(PCR-SSCP) and methylation-specific PCR(MSP) techniques, the structure and hypermethylation status of p16 gene in MM cell lines and patients were analysed. RESULTS: Homozygous deletion of p16 exon 2 was found in KM3 cells. The completely methylated p16 gene and hypermethylation of CPG island were observed in U266, LP1 cell lines and 55.56% of MM patients. CONCLUSION: Methylation of p16 gene is important in the pathogenesis of MM and may provide a new drug target for the treatment of MM.

Aged↗
PubMed2001

[Surgical treatment of abdominal aortic aneurysms: report of 482 cases].

OBJECTIVE: To improve the safety of abdominal aortic aneurysm (AAA) repair. METHOD: The experience of 482 cases of AAA in surgical treatment and endovascular graft exclusion were reviewed from January 1960 to March 2001. RESULTS: Retroperitoneal approach and minimal incision was used for AAA operation. New methods for control of the "neck" of aneurysm, aneurysmectomy and endovascular graft exclusion were applied. The danger of AAA repair obviously decreased. The operative mortality was 5.2% and the five-year survival rate was 74.4%. CONCLUSION: The improvement of surgical and anesthetic techniques made AAA resection rapid and safe.

Adolescent↗
PubMed2001

[Studies on the isolation, culture and DNA identification of mycelia of Tricholoma matsutake].

The tissue isolation for Tricholom matsutake(S Ito et Imai) Sing were made with 8 media in 810 test tubes from different positions of 9 basidiocarps of different source and from mycorrhizae, and soil with the fungi in the studies. The results showed that 94 test tubes of slow-growing mycelia were isolated from lamellae and their success percentages of isolation with media PDAS, PDAW, BM, PDA were 74.4%, 355%, 15.6% and 8.9% respectively. The fast-growing mycelia were easily got from the mycorrhizae and soil related to matsutake. The isolates with different culture characteristics were appraised through DNA fingerprinting comparison with matsutake basidiocarps collected from Jilin province, China and reference isolates presented by matsutake research workers of China and Japan, in which RAPD (Random Amplified Polymorphic DNA)-PCR patterns were sharply prepared using 17 arbitrary decamer nucleotide primers screened. The statistical data indicated that all slow-growing mycelia isolated from lamellae had the same DNA fingerprinting patterns as their origin basidiocarps tissues such as pileus (containing lamellae) and stipe, whose similarity coeffecients all were 1.000, and were therefore identified as true Tricholoma matsutake. However, the fast-growing mycelia or yeast colony were identified as not matsutake. The results suggested that matsutake and its own mycelia have DNA homogeneity, and there exists no any other microbe in the basidiocarps. The results also demonstrated that all matsutake from east China and reference isolates of matsutake from southwest China and Japan were one same species Tricholoma matsutake, whose DNA similarity coeffecients varied from 0.934 to 0.994.

Agaricales↗
PubMed2000

Genetic changes in clinically organ-confined prostate cancer by comparative genomic hybridization.

OBJECTIVES: The genetic basis underlying prostate cancer development and progression is poorly understood. The primary aim of this study was to identify chromosomal regions important for progression in clinically localized prostate cancer removed by radical prostatectomy. METHODS: Comparative genomic hybridization was used for whole genome screening of DNA sequence copy number alterations in 28 pathologically organ-confined tumors (pT2) and 28 tumors with infiltration of the seminal vesicles (pT3b). RESULTS: Comparative genomic hybridization analysis showed on average 2.0 +/- 2.4 chromosomal alterations per tumor with more frequent losses (mean 1.3 +/- 1.8) than gains (mean 0.7 +/- 1.0). The percentage of tumors without alterations was higher in Stage pT2 (21%) than in Stage pT3b (50%). Losses of 8p (21%), 13q (21%), 5q (14%), 16q (14%), and 18q (13%) and gains of Xq (21%) and 8q (9%) were the most prevalent changes. Distinct regional alterations included minimal overlapping regions of loss at 5q13-q21, 6q14-q21, and 18q21-qter. There was only a small increase in the number of alterations from Stage pT2 to Stage pT3b (mean 1.6 +/- 2.3 versus 2.5 +/- 2.4). However, two individual alterations-gain of 8q and loss of 18q-were significantly more frequent in Stage pT3b than in Stage pT2 prostate cancer (P = 0.02 and P = 0.04, respectively), suggesting that genes in these regions may be important for prostate cancer progression. CONCLUSIONS: The detection of chromosome 8q gains and 18q losses and the identification of the corresponding target genes could become a molecular tool for better characterization of clinically localized prostate cancer.

Chromosome Aberrations↗