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Biomedical subjects

W Fu

Publications and source records attributed to W Fu.

At least 91 records · Page 5Linked to original sources
PubMed1997

4-Hydroxynonenal, a product of lipid peroxidation, inhibits dephosphorylation of the microtubule-associated protein tau.

In Alzheimer's disease (AD) the microtubule-associated protein tau is excessively phosphorylated in degenerating neurons, but the mechanisms underlying the increased phosphorylation are unknown. Recent findings suggest that oxidative stress, and membrane lipid peroxidation in particular, contributes to the neurodegenerative process in AD. We now report that following exposure of cultured rat hippocampal neurons to 4-hydroxynonenal (HNE), an aldehydic product of membrane lipid peroxidation, tau is resistant to dephosphorylation. Immunocytochemical and Western blot analyses using phosphorylation-sensitive tau antibodies showed that HNE treatment causes a moderate increase in basal levels of tau phosphorylation, and prevents tau dephosphorylation by alkaline phosphatase in neurons pretreated with the phosphatase inhibitor okadaic acid. Studies with anti-HNE antibodies showed that HNE binds directly to tau, and that HNE immunoreactivity localizes to cell bodies and axons, cell compartments that contain tau. These data suggest a role for HNE in altered tau phosphorylation and neurofibrillary degeneration in AD.

Aldehydes↗
PubMed1997

Neuroprotective action of cycloheximide involves induction of bcl-2 and antioxidant pathways.

The ability of the protein synthesis inhibitor cycloheximide (CHX) to prevent neuronal death in different paradigms has been interpreted to indicate that the cell death process requires synthesis of "killer" proteins. On the other hand, data indicate that neurotrophic factors protect neurons in the same death paradigms by inducing expression of neuroprotective gene products. We now provide evidence that in embryonic rat hippocampal cell cultures, CHX protects neurons against oxidative insults by a mechanism involving induction of neuroprotective gene products including the antiapoptotic gene bcl-2 and antioxidant enzymes. Neuronal survival after exposure to glutamate, FeSO4, and amyloid beta-peptide was increased in cultures pretreated with CHX at concentrations of 50-500 nM; higher and lower concentrations were ineffective. Neuroprotective concentrations of CHX caused only a moderate (20-40%) reduction in overall protein synthesis, and induced an increase in c-fos, c-jun, and bcl-2 mRNAs and protein levels as determined by reverse transcription-PCR analysis and immunocytochemistry, respectively. At neuroprotective CHX concentrations, levels of c-fos heteronuclear RNA increased in parallel with c-fos mRNA, indicating that CHX acts by inducing transcription. Neuroprotective concentrations of CHX suppressed accumulation of H2O2 induced by FeSO4, suggesting activation of antioxidant pathways. Treatment of cultures with an antisense oligodeoxynucleotide directed against bcl-2 mRNA decreased Bcl-2 protein levels and significantly reduced the neuroprotective action of CHX, suggesting that induction of Bcl-2 expression was mechanistically involved in the neuroprotective actions of CHX. In addition, activity levels of the antioxidant enzymes Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, and catalase were significantly increased in cultures exposed to neuroprotective levels of CHX. Our data suggest that low concentrations of CHX can promote neuron survival by inducing increased levels of gene products that function in antioxidant pathways, a neuroprotective mechanism similar to that used by neurotrophic factors.

Amyloid beta-Peptides↗
PubMed1997

Differentiation and functions of T cell subsets.

The Tc1 and Tc2 subsets of CD8+ T effector cells secrete different patterns of cytokines, but have similar functions, including perforin- and Fas-dependent cytotoxicity, and induction of delayed type hypersensitivity (DTH) reactions involving oedema and granulocytic infiltration. The characteristic cytokines of Tc1 (gamma-interferon) and Tc2 (interleukins 4 and 5) are expressed in vivo during the DTH reaction. Tc1 cells that are deficient in cytokine synthesis also induce similar levels of DTH, supporting the lack of correlation between CD8+ T cell cytokine patterns and DTH. CD8+ T cells often produce lower cytokine levels than CD4 cells because the CD8 cells kill their antigen-presenting cells before full stimulation can occur. This effect can be counteracted by increasing the frequency of stimulation, or using perforin-deficient T cells. A multiparameter analysis of cytokine effects on CD8+ T cell differentiation has been initiated, on the basis of the principle that normal immune responses involve complex cytokine mixtures. All combinations of seven cytokines were tested. In some combinations, the combined effect could not have been predicted from individual cytokine functions. Conditions were identified in which each of interleukins 4, 10 and 12 could have opposite effects on CD8+ T cell differentiation.

Animals↗
PubMed1997

Mechanism of the morphological changes induced by staurosporine in rat osteoblasts.

Protein kinase C (PKC) plays an important role in the differentiation of cells, however, little is known about its relationship to bone metabolism. We have previously demonstrated that staurosporine concentration dependently transformed the cultured rat osteoblasts into stellate cells. In this study, we further investigated the possible mechanisms and significance of the morphological changes of osteoblasts induced by staurosporine. The morphological changes induced by staurosporine were inhibited by microtubule depolymerizers or elevated intracellular calcium, however, actin depolymerizers enhanced the effects of staurosporine. Fluorescence labeling showed that staurosporine caused the dissolution of the actin microfilaments, but left the microtubules and vimentin filaments intact. PKC activators partially antagonized the morphological changes induced by staurosporine. Inhibition of protein kinase A or calmodulin-dependent kinase is less effective in the induction of stellate cell formation. These results suggest that the morphological changes of osteoblasts induced by staurosporine may be partly due to PKC inhibition, but other mechanisms may also be involved.

Actin Cytoskeleton↗
PubMed1997

Acute hemodynamic responses to electroconvulsive therapy are not related to the duration of seizure activity.

STUDY OBJECTIVE: To test the hypothesis that the magnitude of the acute hemodynamic response to electroconvulsive therapy (ECT) is related to the duration of the seizure activity in patients receiving different dosages of intravenous (i.v.) lidocaine. DESIGN: Randomized, double-blind, placebo-controlled, cross-over study. SETTING: University-affiliated hospital. PATIENTS: 21 ASA physical status I, II, and III patients undergoing four consecutive maintenance ECT treatments for chronic depression. INTERVENTIONS: Patients received lidocaine 50 mg, 100 mg, 200 mg i.v., or saline prior to induction of anesthesia via a standardized anesthetic technique. MEASUREMENTS AND MAIN RESULTS: Noninvasive blood pressure (BP) and heart rate (HR), as well as the duration of motor and electroencephalographic (EEG) seizure, were measured. The duration of motor and EEG seizures (means +/- SD) were 37 +/- 13 sec and 64 +/- 21 sec, 25 +/- 11 sec and 52 +/- 43 sec, 17 +/- 12 sec and 32 +/- 17 sec, 1 +/- 3 sec and 18 +/- 10 sec in the saline, lidocaine 50 mg, 100 mg, 200 mg groups, respectively. Although the duration of seizure activity was decreased in a dose-related fashion after lidocaine pretreatment, the peak increases in BP and HR were similar in the lidocaine and saline treatment groups. CONCLUSIONS: Despite producing dose-related decreases in the duration of both motor and EEG seizure activity, lidocaine failed to attenuate the acute hemodynamic response to ECT. Thus, the acute hemodynamic response to ECT is not related to the duration of seizure activity.

Aged↗
PubMed1997

Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene.

The Drosophila eyes absent (eya) gene plays an essential role in the events that lead to proper development of the fly eye and embryo. Here we report the analysis of two human and two mouse homologs of the fly eya gene. Sequence comparison reveals a large domain of approximately 270 amino acids in the carboxyl terminus of the predicted mammalian proteins that shows 53% identity between the fly sequence and all of the vertebrate homologs. This Eya-homology domain is of novel sequence, with no previously identified motifs. RNA hybridization studies indicate that the mouse genes are expressed during embryogenesis and in select tissues of the adult. Both mouse Eya genes are expressed in the eye, suggesting that these genes may function in eye development in vertebrates as eya does in the fly. The mouse Eya2 gene maps to chromosome 2 in the region syntenic with human chromosome 20q13, and the mouse Eya2 gene maps to chromosome 4 in the region syntenic with human chromosome 1p36. Our findings support the notion that several families of genes (Pax-6/eyeless, Six-3/sine oculis, and Eya) play related and critical roles in the eye for both files and vertebrates.

Amino Acid Sequence↗
PubMed1997

Placement of tRNA primer on the primer-binding site requires pol gene expression in avian but not murine retroviruses.

In an early step in the retroviral infectious process, reverse transcriptase copies the genomic RNA of the virus into complementary minus-strand DNA. The primer for this synthetic event is a molecule of cellular tRNA, which is annealed by its 3' 18 nucleotides to a region of the genomic RNA termed the primer-binding site (PBS); the sequence of the PBS and hence the identity of the tRNA depend upon the retrovirus species. In addition to the primer tRNA, retrovirus particles contain a substantial number of other tRNA molecules. The latter tRNA population is enriched for the tRNA species which serves as primer for the virus. While there is considerable evidence that the enrichment for the primer species can be attributed to the pol gene product, nothing is known regarding mechanisms of annealing the primer to the PBS. We have analyzed pol- mutants of avian leukosis virus (ALV) and murine leukemia virus (MuLV) for the presence of primer at the PBS in virion genomic RNA. Remarkably, the results were different for the two viruses: the PBS was substantially occupied by primer in MuLV but not in ALV. Previous data indicates that the Pol-dependent enrichment of the primer within the virion is much greater in ALV than in MuLV. We therefore propose that the absence of primer at the PBS in pol- ALV is due to the deficiency of the primer species within the particle. The results suggest that, at least in MuLV, the tRNA is unwound by either the Gag protein or a cellular protein for annealing to the PBS. Further, the C-terminal 17 amino acids of Gag are unnecessary for this function in MuLV.

Animals↗
PubMed1997

Transactivation of proenkephalin gene by HTLV-1 tax1 protein in glial cells: involvement of Fos/Jun complex at an AP-1 element in the proenkephalin gene promoter.

The human T-cell lymphotropic virus type 1 (HTLV-1), an etiologic agent for adult T-cell leukemia, is strongly associated with tropical spastic paraparesis, a chronic neurological disease. The HTLV-1 genome encodes a protein, tax1, an autoregulator of enhanced viral RNA transcription, that also transactivates/represses certain cellular gene promoters. Enkephalins are opioid peptides that function as neurotransmitters and neuroimmunomodulators. We earlier reported that the proenkephalin gene is transactivated by tax1 protein in glial cells. The nucleotide sequence upstream of -190 base pairs in the proenkephalin gene promoter is necessary for maximal transactivation by tax1 while the sequence downstream of -190 bp confers modest activation by tax1. We investigated the cellular transcription factors in tax1 expressing glial cells that associate with the proenkephalin promoter and herein demonstrate the enhanced interaction and involvement of c-Fos/c-Jun proteins in the complexes formed at the AP-1 site. The HTLV-1 tax1 expressing stable glial cell lines produced functional tax1 protein that increased the expression of endogenous proenkephalin gene. The comparative electrophoretic mobility shift and 'supershift' analysis using specific antibodies indicated the enhanced presence of c-Fos and c-Jun proteins in the DNA: protein complex formed at the AP-1 site. The c-Fos protein expression significantly increased in the tax1 expressing glial cells. The tax1 induced c-Fos protein levels and the concurrently increased association of c-Fos/c-Jun transcription factors at the AP-1 site imply a strong functional significance in the activation of proenkephalin gene expression in tax1 expressing glial cells.

Animals↗
PubMed1997

[Combined resection of the pancreas and portal vein replaced by blood vessel prosthesis for pancreatic head carcinoma: report of two cases].

The resectability and prognosis of carcinoma of the pancreatic head are still poor. The higher resectability rate was achieved by combined resection of the pancreas and portal vein. Two patients in whom the portal vein, surrounded but not penetrated by pancreatic carcinoma, was resected and replaced by an expanded Teflon (Gore-Tex) tube (diameter 8 mm). One patient, who survived 32 months without recurrence of disease, had a ultrasonography and CT proved patent graft 6 and 32 months after operation. A second survivor had a patent graft at 20 month. Excision of involved portal vein during pancreatoduodenectomy for carcinoma of the head of the pancreas is a feasible and valid procedure in the absence of metastases. Vein grafting is the best means for portal vein reconstruction. Gore-Tex appears to be suitable prosthesis when the portal vein must be sacrificed.

Adult↗
PubMed1997

[Surgical management of patients with infected vascular prostheses].

We evaluated the therapeutic efficacy of surgical management of patients with infected vascular prostheses. Eight cases of infected vascular prosthetic grafts from 250 prosthetic bypasses were reviewed. The rate of graft infection was 3.2%. Clinical manifestations were localized wound infection with prosthetic graft exposure, anastomotic hemorrhage and gangrene in lower extremity. Treatment included graft removal and debridement; graft removal and primary amputation; graft removal and revascularization; debridement and local graft irrigation. Two cases died from anastomotic hemorrhage and the others recovered. The predisposing factors of vascular prosthetic infection are diabetes mellitus, secondary hemotoma and reoperation in the same position. Conservative treatment efforts without revascularization justifies a more aggressive approach to suspected graft infection.

Adult↗
PubMed1997

[Extraction and sequencing of trace DNA from cornu Cervi pantotrichum].

The trace DNA extraction method was used to extract DNA from the blood, hair, Cornu cervi pantotrichum, hairy antler of the sika deer, Cervus nippon, and penis of Bulbalus bublis and Asinus vulgaris. A 307 bp fragment of mitochondrial DNA cytochrome b gene was amplified with primers L14841 and H15149 for these extractions. The purified PCR products were sequenced by the dideoxy method. DNA sequence obtained from the Cornu cervi pantotrichum is the same as that obtained from the fresh blood and hair of the sika deer, but the sequence of the so-called hairy antler is quite different, implying that it is not from the sika deer. In addition, the phylogenetic relationships among different species are congruent with the traditional known phylogeny.

Animals↗
PubMed1996

The function and properties of the iron-sulfur center in spinach ferredoxin: thioredoxin reductase: a new biological role for iron-sulfur clusters.

Thioredoxin reduction in chloroplasts is catalyzed by a unique class of disulfide reductases which use a [2Fe-2S]2+/+ ferredoxin as the electron donor and contain an Fe-S cluster as the sole prosthetic group in addition to the active-site disulfide. The nature, properties, and function of the Fe-S cluster in spinach ferredoxin:thioredoxin reductase (FTR) have been investigated by the combination of UV/visible absorption, variable-temperature magnetic circular dichroism (MCD), EPR, and resonance Raman (RR) spectroscopies. The results indicate the presence of an S = 0 [4Fe-4S]2+ cluster with complete cysteinyl-S coordination that cannot be reduced at potentials down to -650 mV, but can be oxidized by ferricyanide to an S = 1/2 [4Fe-4S]3+ state (g = 2.09, 2.04, 2.02). The midpoint potential for the [4Fe-4S]3+/2+ couple is estimated to be +420 mV (versus NHE). These results argue against a role for the cluster in mediating electron transport from ferredoxin (Em = -420 mV) to the active-site disulfide (Em = -230 mV, n = 2). An alternative role for the cluster in stabilizing the one-electron-reduced intermediate is suggested by parallel spectroscopic studies of a modified form of the enzyme in which one of the cysteines of the active-site dithiol has been alkylated with N-ethylmaleimide (NEM). NEM-modified FTR is paramagnetic as prepared and exhibits a slow relaxing, S = 1/2 EPR signal, g = 2.11, 2.00, 1.98, that is observable without significant broadening up to 150 K. While the relaxation properties are characteristic of a radical species, MCD, RR, and absorption studies indicate at least partial cluster oxidation to the [4Fe-4S]3+ state. Dye-mediated EPR redox titrations indicate a midpoint potential of -210 mV for the one-electron reduction to a diamagnetic state. By analogy with the properties of the ferricyanide-oxidized [4Fe-4S] cluster in Azotobacter vinelandii 7Fe ferredoxin [Hu, Z., Jollie, D., Burgess, B. K., Stephens, P. J., & Münck, E. (1994) Biochemistry 33, 14475-14485], the spectroscopic and redox properties of NEM-modified FTR are interpreted in terms of a [4Fe-4S]2+ cluster covalently attached through a cluster sulfide to a cysteine-based thiyl radical formed on one of the active-site thiols. A mechanistic scheme for FTR is proposed with similarities to that established for the well-characterized NAD(P)H-dependent flavin-containing disulfide oxidoreductases, but involving sequential one-electron redox processes with the role of the [4Fe-4S]2+ cluster being to stabilize the thiyl radical formed by the initial one-electron reduction of the active-site disulfide. The results indicate a new biological role for Fe-S clusters involving both the stabilization of a thiyl radical intermediate and cluster site-specific chemistry involving a bridging sulfide.

Chloroplasts↗
PubMed1996

Is community financing necessary and feasible for rural China?

The collapse of the Cooperative Medical System (CMS) in China after the agricultural reforms of the early 1980s caused serious concern and doubt about the viability of community financing of basic health care for the low-income population. This paper examines the rise and fall of China's community financing schemes and ascertains the need for and feasibility of community financing. Of the Chinese rural population, 90% now pay out-of-pocket for their health services. Both the problems with the fee-for-service system on the one hand and the observed advantages of the existing community financing schemes on the other indicate the necessity and desirability of revitalizing community financing as a major rural health care reform strategy. However, the feasibility of the community financing approach depends on adequate financial and social resources. Our study found that there are multiple potential funding sources for health care in rural areas, including households, village welfare funds, local enterprises, and the government. We designed several illustrative benefit packages and estimated their costs. It appears that a basic benefit package with high co-insurance would be affordable if funds could be mobilized from multiple sources. More importantly, community financing would require governmental promotion and support.

China↗
PubMed1996

[Sixty years of museum for history of Chinese medicine].

The developmental course of museum for history of Chinese medicine can be divided into 4 stages, namely, Period of Initiation (1937-1949), Period of Development (1950-1965), Period of Stagnation (1966-1976) and Period of Rejuvenation (1977-). The article introduces the dovelopmental course of museum for history of Chinese medicine period by period, supported with plenty of historical facts.

China↗
PubMed1996

[Protective effect of lipid A monoclonal antibody against burn sepsis in rats].

A lipid A monoclonal antibody(mAb) was prepared and it was used to study its protective effect against burn sepsis. Wistar rats were inflicted with 30% TBSA third degress burn, and they were given LPS to mimic early sepsis after burn. The rats were divided randomly into burn with LPS, monoclonal antibody treatment, and control groups. The levels of endotoxin, tumor necrosis factor, light and electron microscopic studies of the morphological changes in the liver were studied. The results showed that the anti-lipid A monoclonal antibody demonstrated capacity to cross-react with several Gram-negative bacteria and their endotoxins. The mAb improved the survival rate of rats and decreased the levels of endotoxin and TNF as well as the liver damage significantly.

Animals↗
PubMed1996

[Changes of circulating Lps and cytokines in burned patients after anti-endotoxin therapy].

OBJECTIVE: Endotoxin as the inciting agent of cytokines and other mediators, whose high level expression correlates with the septic shock and MOF, has been the one of leading causes of death in ICU. METHODS: For treating sepsis and MOF caused by endotoxin, the anti-lipid A of LPS antibody was used, 19 burned patients whose TBSA varied from 50% to 100% were divided into anti-LPS treatment group and nontreated group. RESULTS: The levels of serum endotoxin, IL-6, IL-8, TNF and soluble IL-2R were lower obviously in patients of anti-LPS group than those of nontreated group (P < 0.05). CONCLUSION: Clinical study surggests that anti-lipid A of LPS antibody can act as an therapeutic agent against gram-negative bacterin infection in burned patients.

Adult↗