Biomedical subjects

W Fu

Publications and source records attributed to W Fu.

At least 37 records · Page 2Linked to original sources

PubMed2000

Combinatorial signaling in the specification of unique cell fates.

How multifunctional signals combine to specify unique cell fates during pattern formation is not well understood. Here, we demonstrate that together with the transcription factor Lozenge, the nuclear effectors of the EGFR and Notch signaling pathways directly regulate D-Pax2 transcription in cone cells of the Drosophila eye disc. Moreover, the specificity of D-Pax2 expression can be altered upon genetic manipulation of these inputs. Thus, a relatively small number of temporally and spatially controlled signals received by a set of pluripotent cells can create the unique combinations of activated transcription factors required to regulate target genes and ultimately specify distinct cell fates within this group. We expect that similar mechanisms may specify pattern formation in vertebrate developmental systems that involve intercellular communication.

Animals↗

PubMed2000

Interrelations between plasma homocysteine and intracellular S-adenosylhomocysteine.

S-Adenosylhomocysteine, a potent intracellular methylation inhibitor, is suggested as a potential mediator for hyperhomocysteinemia-related vascular changes. We investigated the effect of acute and chronic hyperhomocysteinemia on intracellular S-adenosylhomocysteine and S-adenosylmethionine in rats and humans. Elevated plasma homocysteine in rats infused with homocysteine produced an increase in S-adenosylhomocysteine (P < 0.001) but not S-adenosylmethionine levels (P > 0.05) in various rat tissues. However intraerythrocyte S-adenosylhomocysteine and S-adenosylmethionine levels were not changed in homocysteine-infused rats and human subjects with experimentally acute hyperhomocysteinemia by methionine loading test. In contrast, erythrocyte S-adenosylhomocysteine levels were significantly higher in chronic renal failure patients, who had chronically elevated plasma homocysteine levels, than in either vascular disease patients or healthy controls (P < 0.05). In conclusion, acute hyperhomocysteinemia can increase intracellular S-adenosylhomocysteine levels in tissues actively involved in homocysteine metabolism. The findings are relevant to homocysteine-related endothelial dysfunction since S-adenosylhomocysteine modulates endothelial cell apoptosis.

Adult↗

PubMed2000

The catalytic subunit of telomerase protects neurons against amyloid beta-peptide-induced apoptosis.

The catalytic subunit of telomerase (TERT) is a specialized reverse transcriptase that has been associated with cell immortalization and cancer. It was reported recently that TERT is expressed in neurons throughout the brain in embryonic and early postnatal development, but is absent from neurons in the adult brain. We now report that suppression of TERT levels and function in embryonic mouse hippocampal neurons in culture using antisense technology and the telomerase inhibitor 3' -azido-2' 3' -dideoxythymidine significantly increases their vulnerability to cell death induced by amyloid beta-peptide, a neurotoxic protein believed to promote neuronal degeneration in Alzheimer's disease. Neurons in which TERT levels were reduced exhibited increased levels of oxidative stress and mitochondrial dysfunction following exposure to amyloid beta-peptide. Overexpression of TERT in pheochromocytoma cells resulted in decreased vulnerability to amyloid beta-peptide-induced apoptosis. Our findings demonstrate a neuroprotective function of TERT in an experimental model relevant to Alzheimer's disease, and suggest the possibility that restoration of TERT expression in neurons in the adult brain may protect against age-related neurodegeneration.

Alzheimer Disease↗

PubMed2000

Rapacuronium recovery characteristics and infusion requirements during inhalation versus propofol-based anaesthesia.

We examined the effect of four maintenance anaesthetics on the neuromuscular blocking activity and spontaneous recovery characteristics after a short-term infusion of rapacuronium. Eighty ASA I-III adult patients undergoing elective surgery were studied at four centres. Anaesthesia was induced with propofol 1.5-2.5 mg kg-1 and fentanyl 1-2 micrograms kg-1, followed by a bolus of rapacuronium 1.5 mg kg-1. The patients were randomized to receive either desflurane (2-4% end-tidal, ET), sevoflurane (0.75-1.5% ET), isoflurane (0.4-0.8% ET), or a propofol infusion (75-150 micrograms kg-1 min-1) for maintenance of anaesthesia in combination with nitrous oxide (60-70%) in oxygen. When the first twitch (T1) of a train-of-four stimulus (using the TOF Guard accelerometer) returned to 5%, an infusion of rapacuronium was started at 3 mg kg-1 h-1 and adjusted to maintain T1/T0 at 10%. The duration of infusion lasted between 45 and 60 min, and the average infusion rates of rapacuronium were similar in all groups, ranging from 1.6 to 2.5 mg kg-1 h-1. There were no significant differences among the groups in the times for T1/T0 to return to 25%, 75% or 90%, or for T4/T1 to return to 70% and 80% upon discontinuation of the infusion. When potent inhalation anaesthetics are used in clinically relevant concentrations for maintenance of anaesthesia, the neuromuscular recovery profile of rapacuronium administered as a variable-rate infusion for up to 1 h is similar to that found with a propofol-based anaesthetic technique.

Adolescent↗

PubMed2000

[Detection of epidermal growth factor receptor gene amplification in human laryngeal carcinomas by means of fluorescence in situ hybridization].

OBJECTIVE: To detect epidermal growth factor receptor(EGFR) gene amplification in human laryngeal carcinoma Hep-2 cell line and laryngeal carcinoma tissues. METHODS: The technique of fluorescence in situ hybridization(FISH). RESULTS: The EGFR gene amplification of a laryngeal carcinoma Hep-2 cell line and 5 laryngeal carcinoma tissues were detected by FISH. In the metaphase chromosome and interphase nuclei of Hep-2 cell line and 2 laryngeal carcinoma tissues, distinct cluster and multiple dot signals were found. In the interphase nuclei of the other 3 laryngeal carcinoma tissues, no increase in the number or extent of the hybrid signals was found. CONCLUSION: Compared with normal diploid cell, the EGFR gene amplification was observed at different levels ranging from 2 to 8 folds in metaphase chromosome and interphase nuclei of Hep-2 cell line and 2 laryngeal carcinoma tissues while no amplification was observed in the other 3 laryngeal carcinoma tissues. The results demonstrate that quantitative detection of amplified gene by FISH in the metaphase chromosome and interphase nuclei is useful for detection of laryngeal carcinoma tissues.

ErbB Receptors↗

PubMed2000

[Microsurgical treatment of medially located tumors of the middle skull base].

OBJECTIVE: To report the results of microsurgical treatment of tumors medially located in the middle skull base. METHODS: The preoperative MRI features, operative approaches, results of operation and postoperative complications in 26 cases were reviewed. RESULTS: Total resection of the tumors was achieved in 12 cases, subtotal resection in 9 cases, partial resection in 6 cases. Two patients died of operation. Cranial nerve palsy remained unchanged in 5 cases and became exacerbated in 5 cases. Clinical improvement was observed in 15 cases. CONCLUSION: The combined frontotemporal-zygomatic approach to remove medially located tumors of the middle skull base is adequate.

Adolescent↗

PubMed2000

[Assessment of extracranial internal carotid artery stenosis by duplex scanning magnetic resonance angiography and digital subtraction angiography: a comparative study].

OBJECTIVE: To investigate the correlation between duplex scanning, magnetic resonance angiography (MRA), and digital subtraction angiography (DSA) in the evaluation of extracranial internal carotid artery (EICA) stenosis. METHODS: All the examinations mentioned-above were performed on 32 patients. According to NASCET, EICA stenosis were classified into four grades: mild (the diameter reduction < 30%), moderate (31% approximately 69%), severe (70% approximately 99%), and total occlusion. RESULTS: One (3.1%) patient suffered from acute brain infarction after DSA. To compare duplex with DSA, Kappa = 0.78, and by the use of a severe or a greater than 30% stenosis as a positive study, the sensitivity, specificity and accuracy were 78%, 95%, 92% and 97%, 91%, 94%, respectively. To compare MRA with DSA, Kappa = 0.73, and with the same criteria, the sensitivity, specificity and accuracy were 78%, 90%, 89% and 97%, 91%, 94%, respectively. In the evaluation where the results of duplex and MRA were in agreement, to compare duplex + MRA with DSA, Kappa = 0.93, and the sensitivity, specificity and accuracy in the diagnosis of severe stenosis were 100%, 95% and 96%, and the accuracy in the diagnosis of > 30% stenosis was 100%. CONCLUSIONS: There is good correlativity between duplex scanning, MRA and DSA in the examination of EICA stenosis. A combination of duplex and MRA with their results in agreement may ultimately eliminate the need of DSA in the evaluation of EICA stenosis.

Aged↗

PubMed2000

[Resection of pelvic retroperitoneal neoplasm and reconstruction of iliac blood vessels: report of 22 cases].

OBJECTIVE: To study the surgical manipulation of iliac blood vessels invaded by pelvic tumors in order to raise the resection rate. METHODS: We reviewed 22 cases of resection for pelvic retroperitoneal tumors along with the reconstruction of iliac blood vessels in our hospital from July 1994 to January 2000. In 22 cases, 8 received operation on the right iliac arteries and veins, and 14 on the left. RESULTS: Follow-up for 4 months to 5 years and 10 months (average 3.6 years) showed that 3 patients had recurrence and needed secondary operation. All the grafts were patent except one vein graft occlusion 7 months after operation. CONCLUSION: Resection of pelvic retroperitoneal neoplasm combined with reconstruction of iliac blood vessels is safe, effective and practical to raise the excision rate and decrease the recurrence rate.

Adult↗

PubMed2000

[A report of two Chinese familial Budd-Chiari syndrome].

OBJECTIVE: To investigate the etiology of two Chinese familial Budd-Chiari syndrome (BCS). METHOD: Four patients with familial BCS (from A and B families), and the other 41 family members were detected by angiography, ultrasound Dopler, etiology analysis and Factor V Leiden (FvL) mutation analysis. RESULT: Four BCS patients were proved by angiography, 2 by ultra sound Dopler in family A. Ten members in family A were varicosis in low extremeties. FvL mutation was detected in 4 of 6 patients and 2 normal family members. A II(2), A III(7, 11, 15,) B II(10) and B III(5) had FvL mutation. The FvL mutations were compatible with Mendel hereditary law. CONCLUSION: FvL mutation may be one of main risk factors and varicosis in low extremeties may be another risk factors for familial BCS.

Adolescent↗

PubMed1999

Superoxide mediates the cell-death-enhancing action of presenilin-1 mutations.

The mechanism whereby mutations in the presenilin-1 (PS-1) gene on chromosome 14 cause early-onset inherited Alzheimer's disease are unknown. We report that PC6 neural cells (a subclone of PC12 cells) expressing PS-1 mutations (M146V and L286V) exhibit increased superoxide production, nitrotyrosine accumulation, and membrane lipid peroxidation following exposure to amyloid beta-peptide 1-42 (Abeta). Mitochondrial calcium accumulation and membrane depolarization following exposure to Abeta were enhanced in cells expressing mutant PS-1. Overexpression of mitochondrial Mn-SOD greatly reduced superoxide production, nitrotyrosine formation, membrane lipid peroxidation, intramitochondrial calcium accumulation, and membrane depolarization following exposure to Abeta and conferred resistance to the apoptosis-enhancing action of the PS-1 mutations. Nitric oxide synthase inhibitors and the peroxynitrite scavenger uric acid blocked the apoptosis-enhancing action of PS-1 mutations. The data suggest pivotal roles for superoxide production and resulting peroxynitrite formation in the pathogenic mechanism of PS-1 mutations.

Alzheimer Disease↗

PubMed1999

Joint action of two RNA degradation pathways controls the timing of maternal transcript elimination at the midblastula transition in Drosophila melanogaster.

Maternally synthesized RNAs program early embryonic development in many animals. These RNAs are degraded rapidly by the midblastula transition (MBT), allowing genetic control of development to pass to zygotically synthesized transcripts. Here we show that in the early embryo of Drosophila melanogaster, there are two independent RNA degradation pathways, either of which is sufficient for transcript elimination. However, only the concerted action of both pathways leads to elimination of transcripts with the correct timing, at the MBT. The first pathway is maternally encoded, is targeted to specific classes of mRNAs through cis-acting elements in the 3'-untranslated region and is conserved in Xenopus laevis. The second pathway is activated 2 h after fertilization and functions together with the maternal pathway to ensure that transcripts are degraded by the MBT.

3' Untranslated Regions↗

PubMed1999

[Loss of heterozygosity and microsatellite instability in laryngeal carcinoma near p16 gene]

OBJECTIVE: To search for the minimal overlap region of tumor suppressor gene in laryngeal carcinoma and discuss the correlation of p16 gene with laryngeal carcinogenesis. METHODS: Five microsatellite polymorphism markers near p16 gene were selected to detect loss of heterozygosity (LOH) and microsatellite instability (MI) in 60 cases of laryngeal squamous cell carcinoma. RESULTS: The frequencies of LOH in 5 markers were less than 23.1%, while the frequencies of MI in 2 markers were higher, with the highest frequency (46.1%) in D9S1752. CONCLUSION: The results suggest that the deletion of p16 gene does not play an important role in the laryngeal carcinogenesis and there may exist a gene around D9S1752 participating in the development of laryngeal carcinoma, which correlates with the mutation of repair gene.

Journal Article↗

PubMed1999

Anti-apoptotic role of telomerase in pheochromocytoma cells.

Telomerase is a protein-RNA enzyme complex that adds a six-base DNA sequence (TTAGGG) to the ends of chromosomes and thereby prevents their shortening. Reduced telomerase activity is associated with cell differentiation and accelerated cellular senescence, whereas increased telomerase activity is associated with cell transformation and immortalization. Because many types of cancer have been associated with reduced apoptosis, whereas cell differentiation and senescence have been associated with increased apoptosis, we tested the hypothesis that telomerase activity is mechanistically involved in the regulation of apoptosis. Levels of telomerase activity in cultured pheochromocytoma cells decreased prior to cell death in cells undergoing apoptosis. Treatment of cells with the oligodeoxynucleotide TTAGGG or with 3,3'-diethyloxadicarbocyanine, agents that inhibit telomerase activity in a concentration-dependent manner, significantly enhanced mitochondrial dysfunction and apoptosis induced by staurosporine, Fe2+ (an oxidative insult), and amyloid beta-peptide (a cytotoxic peptide linked to neuronal apoptosis in Alzheimer's disease). Overexpression of Bcl-2 and the caspase inhibitor zVAD-fmk protected cells against apoptosis in the presence of telomerase inhibitors, suggesting a site of action of telomerase prior to caspase activation and mitochondrial dysfunction. Telomerase activity decreased in cells during the process of nerve growth factor-induced differentiation, and such differentiated cells exhibited increased sensitivity to apoptosis. Our data establish a role for telomerase in suppressing apoptotic signaling cascades and suggest a mechanism whereby telomerase may suppress cellular senescence and promote tumor formation.

Amino Acid Chloromethyl Ketones↗

PubMed1999

Homocysteine enhances neutrophil-endothelial interactions in both cultured human cells and rats In vivo.

Despite intense investigation, mechanisms linking the development of occlusive vascular disease with elevated levels of homocysteine (HCY) are still unclear. The vascular endothelium plays a key role in regulating thrombogenesis and thrombolysis. We hypothesized that vascular lesions in individuals with elevated plasma HCY may be related to a dysfunction of the endothelium triggered by HCY. We investigated the effect of HCY on human neutrophil adhesion to and migration through endothelial monolayers. We also examined the effect of HCY on leukocyte adhesion and migration in mesenteric venules of anesthetized rats. We found that pathophysiological concentrations of HCY in vitro induce increased adhesion between neutrophils and endothelial cells. This contact results in neutrophil migration across the endothelial layer, with concurrent damage and detachment of endothelial cells. In vivo, HCY infused in anesthetized rats caused parallel effects, increasing leukocyte adhesion to and extravasation from mesenteric venules. Our results suggest that extracellular H2O2, generated by adherent neutrophils and/or endothelial cells, is involved in the in vitro endothelial cell damage. The possibility exists that leukocyte-mediated changes in endothelial integrity and function may lead to the vascular disease seen in individuals with elevated plasma HCY.

Animals↗

PubMed1999

The dominant mutation Glazed is a gain-of-function allele of wingless that, similar to loss of APC, interferes with normal eye development.

Dominant mutations have served as invaluable tools for Drosophila geneticists. Here we analyze the dominant eye mutation Glazed (Gla) that was described by T. H. Morgan more than 50 years ago. We show that Gla causes the loss of photoreceptor cells during pupal stages, in a process reminiscent of apoptosis, with a concomitant overproduction of eye pigment. This phenotype is very similar to that caused by the loss of D-APC, a negative regulator of Wingless (Wg) signal transduction. Genetic analyses reveal however that the Gla gain-of-function phenotype can be reverted to wild-type. By generating a P-element-induced revertant of Gla we demonstrate that Gla is allelic to wg. The molecular lesion in Gla indicates that the insertion of a roo retrotransposon leads to ectopic expression of wg during pupal stages. We show that the Gla phenotype is similar to that caused by ectopic expression of Wg driven by the sevenless (sev) enhancer. In both cases Wg exerts its effect, at least in part, by negatively regulating the expression of the Pax2 homolog sparkling (spa). Gla represents not only the first dominant allele of wg, but it may also be the first allele ever described for wg.

Alleles↗

PubMed1999

The endoplasmic reticulum stress-responsive protein GRP78 protects neurons against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis.

The 78-kDa glucose-regulated protein (GRP78) is localized in the endoplasmic reticulum (ER), and its expression is increased by environmental stressors in many types of nonneuronal cells. We report that levels of GRP78 are increased in cultured rat hippocampal neurons exposed to glutamate and oxidative insults (Fe2+ and amyloid beta-peptide) and that treatment of cultures with a GRP78 antisense oligodeoxynucleotide increases neuronal death following exposure to each insult. GRP78 antisense treatment enhanced apoptosis of differentiated PC12 cells following NGF withdrawal or exposure to staurosporine. Pretreatment of hippocampal cells with 2-deoxy-d-glucose, a potent inducer of GRP78 expression, protected neurons against excitotoxic and oxidative injury. GRP78 expression may function to suppress oxidative stress and stabilize calcium homeostasis because treatment with GRP78 antisense resulted in increased levels of reactive oxygen species and intracellular calcium following exposure to glutamate and oxidative insults in hippocampal neurons. Dantrolene (a blocker of ER calcium release), uric acid (an antioxidant), and zVAD-fmk (a caspase inhibitor) each protected neurons against the death-enhancing action of GRP78 antisense. The data suggest that ER stress plays a role in neuronal cell death induced by an array of insults and that GRP78 serves a neuroprotective function.

Animals↗

PubMed1999

Treatment of intraarticular fractures with modified herbert screws (analysis of 69 cases).

Sixty-nine patients with intraarticular fractures were treated with modified Herbert screws between August 1988 and December 1994. They were followed for an average of 20 months (range, 6 months to 4 years). The final results were assessed in terms of patient satisfaction, clinical examination, and radiographic findings. The success rate was 89.8% (62/69). There were no serious complications. The authors believe the advantages of the modified Herbert screw over the Arbeitsgemeinschaft für osteosynthesefrogen cancellous bone screw are many. The modified Herbert screw provides rigid internal fixation with strong purchase on the bone, so that additional immobilization in plaster is seldom required. It can be inserted through articular cartilage and appropriately buried beneath the articular surface. It is not necessary to remove the screw after bone union. This type of fixation can be widely used in the clinical setting.

Adolescent↗

PubMed1999

Degradation of 3-phenylpropionic acid by Haloferax sp. D1227.

Haloferax sp. D1227, isolated from soil contaminated with highly saline oil brine, is the first halophilic archaeon to demonstrate the utilization of aromatic compounds (i.e., benzoic acid, cinnamic acid, and 3-phenylpropionic acid) as sole carbon and energy sources for growth. The degradation of 3-phenylpropionic acid in this strain was studied to examine the strategies utilized by Archaea to metabolize aromatic compounds. Based on our findings of (1) the extracellular accumulation of cinnamic acid, benzoic acid, 3-hydroxybenzoic acid, and gentisic acid in cultures of Haloferax D 1227 grown on 3-phenylpropionic acid, (2) the presence of an 3-phenylpropionylCoA dehydrogenase, (3) the ATP, CoA, and NAD-dependent conversion of cinnamic acid to benzoylCoA, and (4) the presence of gentisate 1,2-dioxygenase, we propose that Haloferax D1227 metabolizes 3-phenylpropionic acid by initial 2-carbon shortening of the side chain to benzoylCoA via a mechanism similar to fatty acid beta-oxidation, followed by aromatic degradation using a gentisate pathway. The upper aliphatic pathway from 3-phenylpropionic acid to benzoic acid is regulated separately from the lower gentisate pathway.

Biodegradation, Environmental↗