Biomedical subjects

W Fu

Publications and source records attributed to W Fu.

At least 55 records · Page 3Linked to original sources

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↗

PubMed1999

Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice.

Excitotoxicity, a form of neuronal injury in which excessive activation of glutamate receptors results in cellular calcium overload, has been implicated in the pathogenesis of Alzheimer disease (AD), although direct evidence is lacking. Mutations in the presenilin-1 (PS1) gene on chromosome 14 are causally linked to many cases of early-onset inherited AD (refs. 5,6). We generated PS1 mutant mice (PS1M146VKI) that express the PS1 M146V targeted allele at normal physiological levels. Although PS1M146VKI mice have no overt mutant phenotype, they are hypersensitive to seizure-induced synaptic degeneration and necrotic neuronal death in the hippocampus. Cultured hippocampal neurons from PS1M146VKI mice have increased vulnerability to death induced by glutamate, which is correlated with perturbed calcium homeostasis, increased oxidative stress and mitochondrial dysfunction. Agents that suppress calcium influx or release and antioxidants protect neurons against the excitotoxic action of the PS1 mutation. These findings establish a direct link between a genetic defect that causes AD and excitotoxic neuronal degeneration, and indicate new avenues for therapeutic intervention in AD patients.

Animals↗

PubMed1999

Spread of drug-resistant Streptococcus pneumoniae in Asian countries: Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study.

Antimicrobial susceptibility of 996 isolates of Streptococcus pneumoniae from clinical specimens was investigated in 11 Asian countries from September 1996 to June 1997. Korea had the greatest frequency of nonsusceptible strains to penicillin with 79.7%, followed by Japan (65.3%), Vietnam (60.8%), Thailand (57.9%), Sri Lanka (41.2%), Taiwan (38.7%), Singapore (23.1%), Indonesia (21.0%), China (9.8%), Malaysia (9.0%), and India (3.8%). Serotypes 23F and 19F were the most common. Pulsed-field gel electrophoresis (PFGE) of 154 isolates from Asian countries showed several major PFGE patterns. The serotype 23F Spanish clone shared the same PFGE pattern with strains from Korea, Japan, Singapore, Taiwan, Thailand, and Malaysia. Fingerprinting analysis of pbp1a, pbp2x, and pbp2b genes of 12 strains from six countries also showed identical fingerprints of penicillin-binding protein genes in most strains. These data suggest the possible introduction and spread of international epidemic clones into Asian countries and the increasing problems of pneumococcal drug resistance in Asian countries for the first time.

Aminoacyltransferases↗

PubMed1999

Dexmedetomidine failed to block the acute hyperdynamic response to electroconvulsive therapy.

BACKGROUND: Orally administered clonidine (0.2-0.3 mg) has been reported to decrease the acute hypertensive response to electroconvulsive therapy (ECT) without prolonging early recovery. This preliminary study was designed to evaluate the acute hemodynamic effects of the investigational alpha2-adrenergic agonist, dexmedetomidine, in patients undergoing a series of ECT treatments. METHODS: Six patients undergoing a series of three to six consecutive ECT treatments were studied according to a randomized, double-blind, placebo-controlled protocol All patients received either saline or dexmedetomidine, 0.5 or 1.0 microg/kg intravenously, 10-30 min before induction of anesthesia for ECT using a standardized anesthesia protocol. In addition to assessing the cardiovascular variables, the duration of seizure activity, degree of sedation, and time to discharge from the Phase I recovery unit were assessed. RESULTS: Although dexmedetomidine produced dose-related increases in the level of sedation before the ECT procedure, it failed to decrease the peak blood pressure and heart rate responses after the ECT treatment. The 0.5 and 1.0 microg/kg doses of dexmedetomidine prolonged the times to orientation and to discharge from the Phase I unit. CONCLUSIONS: The results of this pilot study suggest that dexmedetomidine (0.5-1.0 microg/kg given intravenously) is not beneficial in controlling the acute hyperdynamic response after ECT.

Aged↗

PubMed1999

Use of the cuffed oropharyngeal airway as an alternative to the laryngeal mask airway with positive-pressure ventilation.

BACKGROUND: The cuffed oropharyngeal airway is a modified Guedel-type oral airway with a cuff at its distal end. The objectives of this study were to compare the ability of the cuffed oropharyngeal airway and the laryngeal mask airway to provide positive-pressure ventilation during general anesthesia, and to assess their relative ease of use and ability to reduce total fresh gas flow rates. METHODS: In this prospective, randomized study, a cuffed oropharyngeal airway (n = 25) or a laryngeal mask airway (n = 25) device was inserted after induction of anesthesia intravenously using 2 mg/kg propofol. While anesthesia was maintained with sevoflurane and nitrous oxide, the leak pressure, leak fraction (the fractional difference between the inspired and expired tidal volume), minimum fresh gas flow rate, and need for airway manipulations were determined. The anesthesia provider who inserted the device completed an evaluation form at the end of the 15-min study period. RESULTS: Positive-pressure ventilation was established successfully on the first attempt in 92% of the patients when the cuffed oropharyngeal airway was used and in 88% of the patients when the laryngeal mask airway device was used. However, manipulations of the airway device were necessary more frequently (8 vs. 1 patient; P < 0.05) and the leak pressure was less (22 +/- 6 cm water vs. 26 +/- 5 cm water; P < 0.05) with the cuffed oropharyngeal airway than with the laryngeal mask airway. In addition, the leak fraction (0.19 +/- 0.18 vs. 0.31 +/- 0.22; P < 0.05) and the minimum fresh gas flow rate (1.3 +/- 1.5 vs. 2.4 +/- 2.5; P = 0.12) were less in the laryngeal mask airway group. CONCLUSIONS: Positive-pressure ventilation is possible with the laryngeal mask airway and cuffed oropharyngeal airway devices. Although the cuffed oropharyngeal airway can be inserted easily by inexperienced users with a high first-attempt success rate (> 90%), manipulations of the device may be required to maintain a patent airway. The laryngeal mask airway device allows positive-pressure ventilation at slightly greater peak inspiratory pressures.

Adult↗

PubMed1999

Characterization of the block in replication of nucleocapsid protein zinc finger mutants from moloney murine leukemia virus.

Mutagenesis studies have shown that retroviral nucleocapsid (NC) protein Zn(2+) fingers (-Cys-X(2)-Cys-X(4)-His-X(4)-Cys- [CCHC]) perform multiple functions in the virus life cycle. Moloney murine leukemia virus mutants His 34-->Cys (CCCC) and Cys 39-->His (CCHH) were able to package their genomes normally but were replication defective. Thermal dissociation experiments showed that the CCHH mutant was not defective in genomic RNA dimer structure. Primer tRNA placement on the viral genome and the ability of the tRNA to function in reverse transcription initiation in vitro also appear normal. Some "full-length" DNA copies of the viral genome were synthesized in mutant virus-infected cells. The CCCC and CCHH mutants produced these DNA copies at greatly reduced levels. Circle junction fragments, amplified from two-long-terminal-repeat viral DNA (vDNA) by PCR, were cloned and characterized. Remarkably, it was discovered that vDNA isolated from cells infected with mutant virions had a wide variety of abnormalities at the site at which the two ends of the linear precursor had been ligated to form the circle (i.e., the junction between the 5' end of U3 and the 3' end of U5). In some molecules, bases were missing from regions corresponding to the U3 and U5 linear vDNA termini; in others, the viral sequences extended either beyond the U5 sequences into the primer-binding site and 5' leader or beyond the U3 sequences into the polypurine tract into the env coding region. Still other molecules contained nonviral sequences between the linear vDNA termini. Such defective genomes would certainly be unsuitable substrates for integration. Thus, strict conservation of the CCHC structure in NC is required for infection events prior to and possibly including integration.

Animals↗

PubMed1999

An essential role for the Drosophila Pax2 homolog in the differentiation of adult sensory organs.

The adult peripheral nervous system of Drosophila includes a complex array of mechanosensory organs (bristles) that cover much of the body surface of the fly. The four cells (shaft, socket, sheath, and neuron) which compose each of these organs adopt distinct fates as a result of cell-cell signaling via the Notch (N) pathway. However, the specific mechanisms by which these cells execute their conferred fates are not well understood. Here we show that D-Pax2, the Drosophila homolog of the vertebrate Pax2 gene, has an essential role in the differentiation of the shaft cell. In flies bearing strong loss-of-function mutations in the shaven function of D-Pax2, shaft structures specifically fail to develop. Consistent with this, we find that D-Pax2 protein is expressed in all cells of the bristle lineage during the mitotic (cell fate specification) phase of bristle development, but becomes sharply restricted to the shaft and sheath cells in the post-mitotic (differentiative) phase. Two lines of evidence described here indicate that D-Pax2 expression and function is at least in part downstream of cell fate specification mechanisms such as N signaling. First, we find that the lack of late D-Pax2 expression in the socket cell (the sister of the shaft cell) is controlled by N pathway activity; second, we find that loss of D-Pax2 function is epistatic to the socket-to-shaft cell fate transformation caused by reduced N signaling. Finally, we show that misexpression of D-Pax2 is sufficient to induce the production of ectopic shaft structures. From these results, we propose that D-Pax2 is a high-level transcriptional regulator of the shaft cell differentiation program, and acts downstream of the N signaling pathway as a specific link between cell fate determination and cell differentiation in the bristle lineage.

Alleles↗

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.

Gene Deletion↗

PubMed1999

[An introductory clinical trial of three-monthly injectable contraceptive-depot medroxyprogesterone acetate].

OBJECTIVE: To evaluate contraceptive efficacy, continuative rate of use, side effects and acceptability of depot medroxyprogesterone acetate (DMPA) injectable contraception preparation in Chinese women. METHOD: This was an open study. One thousand nine hundred and eighty-five women acquiring contraception received DMPA injection after obtaining informed consent and were followed-up every 3-month up to one year. RESULTS: The total experience accumulated was 1,731.7 women-year with DMPA for 1,985 users. The one year continuation rate was 77.4%. Three subjects became pregnant, the one year accumulative life table failure rate was 0.2%. The accumulative discontinuation rates at one year for other reasons were amenorrhoea (4.8%), bleeding related (13.4%), other medical reasons (2.6%), other personal reasons (2.1%) and lost to follow-up (1.6%). The main complaints were irregular bleeding, amenorrhoea and prolonged bleeding. Lactating women had significantly lower rate of complaint. CONCLUSION: DMPA is a highly effective long-acting contraceptive, it could have good acceptability, especially for lactating women, under the well consultation.

Adolescent↗

PubMed1999

[Pathogenetic effect of platelet activating factor on enterogenic endotoxemia after burn].

OBJECTIVE: To investigate the effects of platelet activating factor (PAF) on the occurrence of enterogenic endotoxemia after burn. METHODS: The relationship between changes of PAF and enterogenic endotoxima was observed on a model of rats with 30% TBSA III degree burn. RESULTS: The intestinal permeability and plasma endotoxin were significantly elevated and were positively correlated with the increase of PAF in the intestinal tissue and blood. PAF antagonist treatment significantly decreased the intestinal permeability and the levels of plasma endotoxin. After intravenous injection of enogenous PAF to healthy rats, the intestinal permeability and plasma endotoxin were also markedly increased, which was significantly depended on the dose of PAF. CONCLUSION: PAF is one of the important factors for the occurrence of postburn enterogenic endotoximia.

Animals↗

PubMed1999

[Shi Ji Yao Yu, the earliest extant monograph on TCM nursery].

Nursery of traditional Chinese medicine (NTCM) has a long history. However, due to the change and influence of the era, society, life style, and many other factors, NTCM did not become an independent discipline for a long period. Although there have been many articles about NTCM appearing in various historical books of traditional Chinese medicine, books specializing on NTCM were not available until later. The earliest ancient book, which is still currently available, describing NTCM in details is the "Shi Ji Yao Yu" written by Qian Xiang in the Qing Dynasty. The book explains the key issues of taking care of a patient's emotional well-being, life style, diet, illness, and drug administration which are of great practical significance now and for the future.

Books↗

PubMed1999

[FHIT gene is abnormal in Chinese lung cancers].

OBJECTIVE: To determine whether the FHIT gene at 3p14.2 is abnormal in Chinese lung cancers. METHODS: Matched normal and cancerous tissues from 21 cases of primary pulmonary squamous cell carcinoma (SQC) and 10 cases of adenocarcinoma (ADC) were obtained immediately after surgery. Total RNA was extracted and the FHIT gene was detected by RT-PCR and DNA sequencing technology. RESULTS: Normal-sized FHIT transcript was detected in all 31 cases of normal matched tissues. Aberrant transcripts were observed in 15 (48%) of 31 cases of cancerous tissues, 57% (12/21) in SQC and 33% (3/10) in ADC, respectively. All the abnormal transcripts observed lacked exon 5, the first coding exon. The sequence analyses of the aberrant cDNAs revealed deletions of various regions between exon 4 and 10. A synonymous mutation in E8, codon98CAT(H)-->CAC(H), was found in a SQC. CONCLUSION: The high deletion rate of the FHIT gene in Chinese lung cancer supports the hypothesis that the FHIT gene alteration is involved in tumorigenic development of human neoplasm.

Acid Anhydride Hydrolases↗

PubMed1999

[FHIT gene is abnormal in laryngeal carcinoma].

OBJECTIVE: To determine the role of FHIT gene in laryngeal carcinogenesis. METHODS: Laryngeal cancer cell line Hep-2, HeLa cell line and 80 primary tumors from patients with laryngeal cancer were studied by means of RT-PCR, sequencing and microsatellite analysis. RESULTS: Abnormal transcripts of FHIT gene were found in the two cell lines and 70% (14/20) of primary laryngeal carcinomas. Aberrant laryngeal tumor transcripts often lack more than two exons of FHIT gene. Microsatellite analysis showed that both loss of heterozygosity and microsatellite instability of FHIT gene existed in laryngeal carcinoma and the former was more common. CONCLUSION: FHIT gene participates in the laryngeal carcinogenesis and may be one of the candidate tumor suppressor genes.

Acid Anhydride Hydrolases↗

PubMed1999

[The detection and clinical significance of telomerase activity in supraglottic carcinomas].

OBJECTIVE: To study the expression and significance of telomerase activity in laryngeal carcinoma. METHOD: We detected telomerase activity of HEP-2 cell line, 26 cases of supraglottic carcinoma tissues and 15 cases of peri-carcinoma tissues with PCR-based assay designated TRAP (for telomeric repeat amplification protocol). RESULT: The telomerase positive rate of supraglottic carcinoma 84.6% (22/26) was obvious higher than that of peri-carcinoma 40% (6/15), P < 0.01. No significant differences in positive rates were found among different groups divided according to clinical stage or metastasis of cervical lymph node, P > 0.05. CONCLUSION: Telomerase activation is related to immortalization process, though not much helpful in diagnosis of supraglottic carcinoma.

Adult↗

PubMed1999

[Antibiotic resistance and plasmid profiles of Vibrio isolates from cultured Sparus sarba].

A total of 51 potential pathogenic vibrios were isolated from moribund silver seabream Sparus sarba, which were collected from local fish farms of Hong Kong. All the isolates were classified and identified as 7 species by the API 20 E system and the scheme of Alsina & Blanch. These species were Vibrio alginolyticus (24 strains), Vibrio vulnificus (12 strains), Vibrio parahaemolyticus(7 strains), Vibrio logei(4 strains), Vibrio pelagius II(2 strains), Vibrio fluvialis (1 strains) and Vibrio meditterranei (1 strains). Among these isolates, the three predominant species (V. alginolyticus, V. vulnificus and V. parahaemolyticus) were confirmed to be virulent to sea bream by experimental challenge. All isolates were also screened for plasmid DNA by agarose gel electrophoresis and tested for susceptibility to 16 antimicrobial agents by the agar dilution method. Of the 51 isolates examined, all strains were sensitive to ceftriaxone, streptomycin, nalidixic acid and rifampicin, and almost all were sensitive to ceftazidime, netilimicin, chloramphenicol and sulfamethoxazole except one or two strains. Most isolates were resistant to ampicillin (60. 8%), cefuroxime (66.7%), amikacin(55%), kanamycin(58.8%) and trimethoprinm (76.5%). Fifteen of the 51 isolates harboured 1-4 plasmids, with sizes ranging from 9 to 123 kb. Both the plasmids and the associated antimicrobial resistance (ampicillin, cefuroxime and trimethoprim) of 9 isolates could be transferred to recipient by single-step conjugation, however, the frequencies were very low, ranging from 10(-11) to 10(-9). The present results indicate that resistance to these antibiotics is chromosomal.

Animals↗

PubMed1998

Protein modification by the lipid peroxidation product 4-hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients.

We report increased modification of proteins by 4-hydroxynonenal (HNE), a product of membrane lipid peroxidation, in the lumbar spinal cord of sporadic amyotrophic lateral sclerosis (ALS) patients versus that of neurologically normal controls. By immunohistochemistry, HNE-protein modification was detected in ventral horn motor neurons, and immunoprecipitation analysis revealed that one of the proteins modified by HNE was the astrocytic glutamate transporter EAAT2. Given that the function of proteins modified by HNE can be severely compromised as previously demonstrated for glutamate transporters in cortical synaptosome preparations, our findings suggest a scenario in which oxidative stress leads to the production of HNE, impairment of glutamate transport, and excitotoxic motor neuron degeneration in ALS.

Aged↗