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Biomedical subjects

F Su

Publications and source records attributed to F Su.

At least 19 recordsLinked to original sources
PubMed2001

Regulation of pro-inflammatory cytokine expression by curcumin in hyaline membrane disease (HMD).

Persistent expression of pro-inflammatory cytokines is believed to play a major role in the pathogenesis of chronic lung disease (CLD) in premature infants. Inhibition of pro-inflammatory cytokine production in the lungs of preterm newborns may result in the attenuation of CLD. Curcumin is a naturally occurring phenolic compound derived from the food spice tumeric with broad based in vitro anti-inflammatory properties. In this study lung inflammatory cells from preterm newborns at risk for the development of CLD were derived via modified broncho-alveolar lavage and stimulated ex vivo with lipopolysaccharide (LPS) (10 ng/ml). Curcumin was added to these cultures at 0, 0.5 and 20 uM concentrations. Pro-inflammatory cytokine, TNFalpha, IL-1beta and IL-8 protein was measured from the culture supernatants 12 hours post culture. For control, adult peripheral blood mononuclear cells (PBMC) were cultured under the same conditions. Both neonatal lung inflammatory cells and adult PBMC produced high levels of pro-inflammatory cytokines in response to LPS. Curcumin produced significant inhibition of IL-1beta and IL-8 but minimal inhibition of TNFalpha expression by preterm lung inflammatory cells at 20 uM concentrations. Adult PBMC expression of IL-8 was significantly inhibited by curcumin at 20 uM concentrations. Therefore, curcumin inhibits pro-inflammatory cytokine production (TNFalpha, IL-1beta and IL-8) by lung inflammatory cells ex vivo. Pathways involved with curcumin regulation of these cytokines are developmentally intact and functional in premature infants. Curcumin may be effective as a therapeutic agent in the attenuation of CLD.

Adult↗
PubMed2001

Negative control of p53 by Sir2alpha promotes cell survival under stress.

The NAD-dependent histone deacetylation of Sir2 connects cellular metabolism with gene silencing as well as aging in yeast. Here, we show that mammalian Sir2alpha physically interacts with p53 and attenuates p53-mediated functions. Nicotinamide (Vitamin B3) inhibits an NAD-dependent p53 deacetylation induced by Sir2alpha, and also enhances the p53 acetylation levels in vivo. Furthermore, Sir2alpha represses p53-dependent apoptosis in response to DNA damage and oxidative stress, whereas expression of a Sir2alpha point mutant increases the sensitivity of cells in the stress response. Thus, our findings implicate a p53 regulatory pathway mediated by mammalian Sir2alpha. These results have significant implications regarding an important role for Sir2alpha in modulating the sensitivity of cells in p53-dependent apoptotic response and the possible effect in cancer therapy.

Animals↗
PubMed2001

Soluble Fas ligand released by colon adenocarcinoma cells induces host lymphocyte apoptosis: an active mode of immune evasion in colon cancer.

Expression of membrane-bound Fas ligand (mFasL) on colon cancer cells serves as a potential mechanism to inhibit host immune function by inducing apoptosis of host lymphocytes. Membrane-bound FasL can be cleaved and released as a soluble mediator (sFasL), which may spread the apoptosis induction effect. Our study examined whether colon adenocarcinoma cells release sFasL, and induce apoptosis of host lymphocytes without direct cell-cell contact. In 12 consecutive patients with colon adenocarcinoma mFasL was identified in the tumours, sFasL was measured in the sera and apoptosis identified in tumour-infiltrating and peripheral blood lymphocytes. To analyse the function of sFasL, colon cancer cells were primarily cultured; sFasL was isolated from supernatants, measured, incubated with Fas-bearing Jurkat cells, and the resulting apoptosis was analysed. Serum levels of sFasL were significantly elevated in all colon cancer patients with mFasL expression in tumour tissues (n = 8). In these patients, the number of apoptotic lymphocytes was significantly increased within tumour and peripheral blood. Furthermore, sFasL was present in the corresponding supernatants and induced apoptosis of Jurkat cells in a dose-dependent manner. These findings suggest that mFasL-positive colon cancer cells release sFasL, and thus may induce apoptosis of host lymphocytes as a potential mechanism for immune evasion.

Adenocarcinoma↗
PubMed2001

Attenuation of morphine dependence and withdrawal in rats by venlafaxine, a serotonin and noradrenaline reuptake inhibitor.

The effects of venlafaxine, a novel serotonin and adrenaline reuptake inhibitor, on the morphine withdrawal and activation of morphine conditioned place preference (CPP), were investigated in rats. Our results showed that the most morphine withdrawal signs, including jumping, writhing, shakes, exploring, lacrimation, piloerection, irritability, and diarrhea, were attenuated by pretreatment with 10 or 20 mg/kg venlafaxine. To investigate the effects of venlafaxine on relapse to opiate dependence, the morphine CPP was used and a dopamine D2 antagonist sulpiride was selected as a control drug. The morphine CPP disappeared following a 28-day drug-free period and appeared again after given a single injection of 1 mg/kg morphine. Acute treatment with sulpiride (25 or 50 mg/kg, i.p.) 30 min prior to 1 mg/kg morphine injection significantly blocked the reacquisition of CPP, while venlafaxine (10 or 20 mg/kg, i.p.) did not show significant effect. However, chronic treatment with venlafaxine (5 or 10 mg/kg, i.p. twice, daily, for seven consecutive days) significantly attenuated the reacquisition of morphine CPP, whereas chronic treatment with sulpiride (10 or 20 mg/kg, i.p.) have no significant effect. Our results demonstrated for the first time that venlafaxine strongly attenuates morphine withdrawal and morphine-induced reaquisition of

Adrenergic Uptake Inhibitors↗
PubMed2001

Blocking CTL-based cytotoxic pathways reduces apoptosis of transplanted hepatocytes.

BACKGROUND: A major obstacle in allogenic hepatocyte transplantation is increased apoptosis of grafted cells due to CTL-based cytotoxicity. However, whether blockade of Fas- and granzyme-mediated pathways of CTL-based cytotoxicity may provide immune protection to transplanted hepatocytes is poorly defined. Our study aimed to reduce apoptosis of allogenic transplanted hepatocytes by inhibiting granzyme B (GraB) activity and blocking Fas-FasL interaction. MATERIALS AND METHODS: Hepatocyte transplantation was performed by inoculating isolated liver cells from ACI rats (allogenic) or Lewis rats (syngenic) into the spleens of Lewis rats. Recipients were treated with FLIM58, an inhibitory anti-FasL mAb, and GraB inhibitor I alone or a combination of the two drugs for 5 days after transplantation, and were sacrificed at Day 7. Apoptosis of transplanted hepatocytes was detected in situ by TUNEL assay and M30 immunostaining. Glutamate dehydrogenase (GLDH) activity in recipient spleens was examined to evaluate survival of transplanted cells. Recipient spleens were assayed for FasL level with Western blotting and for GraB activity by hydrolysis of GraB substrate. RESULTS: FLIM58 or GraB inhibitor I significantly reduced the percentage of TUNEL-positive and M30-positive hepatocytes and markedly increased GLDH levels in allogenic, but not syngenic, recipient spleens. These effects were more pronounced when the two drugs were used in combination (P < 0.05). Additionally, elevation of FasL and GraB levels in allogenic recipient spleens can be significantly reduced by FLIM58 and GraB inhibitor I, respectively. CONCLUSIONS: Inhibition of GraB activity and blockade of Fas-FasL interaction reduce the apoptosis of allogenic transplanted hepatocytes, and thus improve their survival.

Animals↗
PubMed2001

Rare occurrence of metastatic colorectal cancers in livers with replicative hepatitis B infection.

BACKGROUND: It has been demonstrated that colorectal carcinomas rarely metastasize to diseased livers. However, this phenomenon has not been thoroughly evaluated in patients with various forms of chronic hepatitis B virus (HBV) infection. Therefore, the present study examined the relationship between the incidence of hepatic metastasis of colorectal carcinomas and chronic HBV infection, with emphasis on the influence of HBV viral replication and chronic liver damage. METHODS: We analyzed the clinicopathological data of 512 patients undergoing surgical treatment of colorectal carcinomas at our department from 1992 to 1998. Among these cases, 74 had chronic HBV infection, including 28 cases with HBV replication and 21 with chronic liver damage. RESULTS: The incidence of liver metastasis in the HBV infection group (13.5%) was significantly lower than that of the noninfection group (27.1%, P <0.05). In addition, patients with HBV infection survived longer than those without infection (P = 0.018). Furthermore, liver metastatic rate in patients with HBV replication (3.6%) was lower than those without virus replication (19.6%, P <0.05). In contrast, there was no significant difference in liver metastasis between HBV infected patients with or without chronic liver damage (P >0.05). CONCLUSIONS: Chronic HBV infection with viral replication reduces hepatic metastasis of colorectal cancer, and thus prolongs the survival of patients.

Carcinoma↗
PubMed2001

Effect of slip on movement of body center of mass relative to base of support.

OBJECTIVE: The purpose is to investigate the effect of balance conditions and slippery perturbation on the position and velocity of the body's center of mass relative to the body's base of support. DESIGN: Twenty-two young and healthful subjects were investigated while their walk was perturbed by a soap patch applied over a force plate. A safety harness was used to prevent the subject from falling on knee or buttock. BACKGROUND: Appropriate postural response to meet physiological biomechanical requirements is mandatory in restoration of balance upon slip. METHODS: Twenty-two healthy subjects dressed with safety harness walked first without and then with slippery perturbation, guided by a metronome at 120 steps/min and 90 steps/min cadence. Data were collected from a motion analysis system and force plates. RESULTS: For slippery perturbation, the displacement and velocity of center of mass with respect to base of support became smaller from heel strike to contralateral toe off. Subject's balance condition correlated significantly to the displacement of center of mass with respect to base of support (r=-0.51 at 120 steps/min and r=-0.471 at 90 steps/min), as well as the velocity (r=-0.834 at 120 steps/min, r=-0.673 at 90 steps/min) at contralateral toe off. CONCLUSIONS: For slip during walking, smaller excursion and faster velocity of center of mass with respect to base of support were important for subjects regaining balance from heel strike to contralateral toe off. The critical time for subjects regaining stability is the first double support phase of the gait cycle. RELEVANCE: It is confirmed that two variables, the displacement and the velocity of center of mass with respect to base of support, are valuable biomechanical factors and provide quantifiable determination for investigation of the balance condition in slipping.

Accidental Falls↗
PubMed2001

Fuzzy clustering of gait patterns of patients after ankle arthrodesis based on kinematic parameters.

Kinematic parameters for 10 normal subjects and 10 patients with ankle arthrodesis are grouped using the fuzzy cluster paradigm. The features chosen for clustering are Euler angles of the sagittal plane in the hindfoot, the forefoot and combined hindfoot and forefoot joints. Gait patterns are identified using information provided by cluster validity techniques, giving three, three and two clusters for the hindfoot, forefoot and combined hindfoot and forefoot joints, respectively. The cluster centers represent distinct walking strategies adopted by normal subjects and patients after ankle arthrodesis. Utilizing angle values normalized by gait cycle, it is possible to classify any subject and to generate an individual's membership value for each of the clusters. The clinical utility of the fuzzy clustering approach is demonstrated with data for subjects with ankle arthrodesis, where changes in membership of the clusters provide an objective technique for measuring changes of gait pattern after ankle arthrodesis. This approach can be adopted to study other clinical entities where different cluster centers would be established using the algorithm provided in this study.

Adult↗
PubMed2001

Adenovirus-mediated Bcl-2 gene transfer inhibits apoptosis and promotes survival of allogeneic transplanted hepatocytes.

BACKGROUND: Donor hepatocyte apoptosis that is induced by host cytotoxic T lymphocytes (CTLs) limits the application of hepatocyte transplantation. Hepatocytes from Bcl-2 transgenic mice can resist the lethal effect of anti-Fas antibody. However, the anti-apoptotic effect of Bcl-2 expression on allogeneic transplanted hepatocytes remains elusive. This study tested the feasibility of Bcl-2 gene transfer as an approach to inhibit CTL-mediated apoptosis in allogeneic transplanted hepatocytes. METHODS: An adenovirus vector that encoded human Bcl-2 gene (AdCMVhBcl-2) was used to transfect cultured rat hepatocytes, which were then transplanted into allogeneic spleens. DNA fragmentation and caspase-3 activation were examined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay and immunohistochemistry for active caspase-3, respectively. Cocultivation of hepatocytes and allogeneic CD8(+) T lymphocytes was performed, and cytotoxicity on hepatocytes was examined by alanine transaminase release. RESULTS: Bcl-2 gene transfer inhibited apoptosis and increased liver-associated enzyme activities in allogeneic transplanted hepatocytes, which were associated with inhibition of caspase-3 activation. Alanine transaminase release in hBcl-2 modified hepatocytes was lower compared with controls, which could not be further decreased by inhibition of Fas ligand and granzyme B. CONCLUSIONS: Adenovirus-mediated Bcl-2 gene transfer blocks CTL-mediated apoptosis in allogeneic hepatocytes by inhibition of caspase-3 activation. Bcl-2 gene transfer could be used to promote survival of transplanted hepatocytes.

Adenoviridae↗
PubMed2001

Role of NF-kappaB and myc proteins in apoptosis induced by hepatitis B virus HBx protein.

Chronic infection with hepatitis B virus (HBV) promotes a high level of liver disease and cancer in humans. The HBV HBx gene encodes a small regulatory protein that is essential for viral replication and is suspected to play a role in viral pathogenesis. HBx stimulates cytoplasmic signal transduction pathways, moderately stimulates a number of transcription factors, including several nuclear factors, and in certain settings sensitizes cells to apoptosis by proapoptotic stimuli, including tumor necrosis factor alpha (TNF-alpha) and etopocide. Paradoxically, HBx activates members of the NF-kappaB transcription factor family, some of which are antiapoptotic in function. HBx induces expression of Myc protein family members in certain settings, and Myc can sensitize cells to killing by TNF-alpha. We therefore examined the roles of NF-kappaB, c-Myc, and TNF-alpha in apoptotic killing of cells by HBx. RelA/NF-kappaB is shown to be induced by HBx and to suppress HBx-mediated apoptosis. HBx also induces c-Rel/NF-kappaB, which can promote apoptotic cell death in some contexts or block it in others. Induction of c-Rel by HBx was found to inhibit its ability to directly mediate apoptotic killing of cells. Thus, HBx induction of NF-kappaB family members masks its ability to directly mediate apoptosis, whereas ablation of NF-kappaB reveals it. Investigation of the role of Myc protein demonstrates that overexpression of Myc is essential for acute sensitization of cells to killing by HBx plus TNF-alpha. This study therefore defines a specific set of parameters which must be met for HBx to possibly contribute to HBV pathogenesis.

3T3 Cells↗
PubMed2001

[Clinical study on effect of qihuang oral liquid to enteric flora disturbance and serum endotoxin level in patients of liver cirrhosis].

OBJECTIVE: To study the effect of Qihuang oral liquid (QHOL) in treating enteric flora disturbance and serum endotoxin level of liver cirrhosis patients. METHODS: Seventy patients suffering from liver cirrhosis were randomized into the control group and the QHOL treated group. The symptomatic changes, quantitative determination of anaerobic and aerobic flora in feces as well as serum endotoxin level were observed before and after treatment. RESULTS: In comparison with the control group, the treated group revealed a significantly better effects (P < 0.05) in the following parameters: (1) reduction in aerobic and increase in anaerobic flora, thus to improve the ratio of enteric flora; (2) improvement in clinical symptoms; (3) lowering in serum endotoxin level. CONCLUSION: QHOL might alter the ratio of enteric flora by increasing anaerobics, a significant lowering of enterogenic endotoxin production and absorption, hence obviously reduced serum endotoxin level was induced which might correlate to the improvement in symptoms and liver damage.

Adult↗
PubMed2000

Deacetylation of p53 modulates its effect on cell growth and apoptosis.

The p53 tumour suppressor is a transcriptional factor whose activity is modulated by protein stability and post-translational modifications including acetylation. The mechanism by which acetylated p53 is maintained in vivo remains unclear. Here we show that the deacetylation of p53 is mediated by an histone deacetylase-1 (HDAC1)-containing complex. We have also purified a p53 target protein in the deacetylase complexes (designated PID; but identical to metastasis-associated protein 2 (MTA2)), which has been identified as a component of the NuRD complex. PID specifically interacts with p53 both in vitro and in vivo, and its expression reduces significantly the steady-state levels of acetylated p53. PID expression strongly represses p53-dependent transcriptional activation, and, notably, it modulates p53-mediated cell growth arrest and apoptosis. These results show that deacetylation and functional interactions by the PID/MTA2-associated NuRD complex may represent an important pathway to regulate p53 function.

Acetylation↗
PubMed2000

Cure of human carcinoma xenografts by a single dose of pretargeted yttrium-90 with negligible toxicity.

A covalent conjugate (NR-LU-10/SA) was prepared between streptavidin (SA) and NR-LU-10, a mAb that binds an antigen expressed on the surface of most human carcinomas. NR-LU-10/SA was injected into nude mice bearing human tumor xenografts. Injection of biotinylated galactosyl-human serum albumin reduced the circulating levels of conjugate by 95%. Subsequent administration of (90)Y-1,4,7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin achieved peak uptake at the tumor within 2 hr while >80% of the radioactivity was eliminated in the urine. A single dose of 600-800 microCi of (90)Y-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin produced cures in 10/10 mice with established (>200 mm(3)) s.c. human small cell lung or colon cancer xenografts and 8/10 cures in mice with human breast cancer xenografts without significant toxicity.

Animals↗
PubMed2000

Laser-induced gene expression in specific cells of transgenic zebrafish.

Over the past few years, a number of studies have described the generation of transgenic lines of zebrafish in which expression of reporters was driven by a variety of promoters. These lines opened up the real possibility that transgenics could be used to complement the genetic analysis of zebrafish development. Transgenic lines in which the expression of genes can be regulated both in space and time would be especially useful. Therefore, we have cloned the zebrafish promoter for the inducible hsp70 gene and made stable transgenic lines of zebrafish that express the reporter green fluorescent protein gene under the control of a hsp70 promoter. At normal temperatures, green fluorescent protein is not detectable in transgenic embryos with the exception of the lens, but is robustly expressed throughout the embryo following an increase in ambient temperature. Furthermore, we have taken advantage of the accessibility and optical clarity of the embryos to express green fluorescent protein in individual cells by focussing a sublethal laser microbeam onto them. The targeted cells appear to develop normally: cells migrate normally, neurons project axons that follow normal pathways, and progenitor cells divide and give rise to normal progeny cells. By generating other transgenic lines in which the hsp70 promoter regulates genes of interest, it should be possible to examine the in vivo activity of the gene products by laser-inducing specific cells to express them in zebrafish embryos. As a first test, we laser-induced single muscle cells to make zebrafish Sema3A1, a semaphorin that is repulsive for specific growth cones, in a hsp70-sema3A1 transgenic line of zebrafish and found that extension by the motor axons was retarded by the induced muscle.

Animals↗
PubMed2000

[Sentinel lymph node biopsy in breast cancer: value for predicting the status of axillary node].

OBJECTIVE: To evaluate feasibility and accuracy of intraoperative lymphatic mapping with sentinel lymphadenectomy (SLND) for predicting axillary status in patients with breast cancer. METHODS: Our study enrolled 52 patients with primary breast cancer, clinically and ultrasonographically negative axillae. Mapping procedures and SLND were performed using methylene blue injected at the primary breast cancer site followed by axillary lymph node dissection (ALND). Sentinel node (SN) was examined by using frozen sections intraoperatively and all of the axillary lymph nodes were evaluated pathologically (HE) after operation. RESULTS: Sentinel nodes were identified in 46 (88.5%) of 52 procedures and nodal status accurately predicted axillary in 44 (95.7%) of 46 cases. In 2 (4.3%) of 46 cases, the SN was false-negative. The overall sensitivity of the SN technique was 90.9%, with a specificity of 100%. The overall positive and negative predictive values were 100% and 92.3%, respectively. In 15 (75%) of 20 cases of clinically negatively and pathologically positive axillary, the SN was the only tumor-involved lymph node identified. CONCLUSION: Our study indicates that intraoperative lymphatic mapping using a vital dye and SLND can accurately predict the axillary status of primary breast cancer patients with clinically and ultrasonographically negative axillae.

Adult↗
PubMed2000

[Influence of organic modifier on the retention behaviour in soil leaching column chromatography].

The relationship between capacity factors (k') of 55 nonionic compounds and broad methanol volume percentage (psi) of methanol-water eluent in soil leaching column chromatography (SLCC) was systematically investigated. The compounds consist of 11 chlorobenzenes, 14 alkylbenzenes, 22 polyphenyls and polycyclic aromatic hydrocarbons, and 8 pesticides. Reference soil was dry-packed into a stainless steel chromatographic column (10 mm i.d. x 100 mm) by a homemade pressurizing device, and isocratic methanolwater mixture with psi from 0.0 to 0.80 eluated through the column at a flow-rate of 1 mL.min-1. The column was thermostated at (25.0 +/- 0.1) degree C, and chromatographic peak was monitored by an online ultraviolet detector. The results show that both equations, log k' = log k'w + a psi + b psi 2(1) and log k' = log k'w - S psi (2), well fit the retention values. Equation (2) can be used practically due to few experimental data needed and simpler in formula. Explanation is also given for the existence of the carbon (or chlorine) number rule for two classes of homologous series (i.e. methylbenzenes, n-alkylbenzenes) and weak-polar chlorobenzenes in the SLCC process. The slope and intercept of the rule are also well correlated, and both decreases linearly with increasing eluent psi value.

Chlorobenzenes↗
PubMed1999

Regulation of CCR5 and CXCR4 expression by type 1 and type 2 cytokines: CCR5 expression is downregulated by IL-10 in CD4-positive lymphocytes.

HIV-1 transmission and disease progression is, in general, characterized by initial predominance of macrophage tropic, non-syncytium-inducing strains followed by a switch to T-cell tropic, syncytium-inducing strains. Using sensitive, quantitative kinetic RT-PCR, we examined cytokine regulation of tropism-specific HIV-1 coreceptor expression in PBMCs from HIV-1-seronegative individuals. Proinflammatory (TNF-alpha and IL-12) and type 1 cytokines (IFN-gamma and IL-2) significantly upregulated CCR5 (wt allele) mRNA expression in CCR5 homozygous wild-type (wt/wt) and heterozygous individuals (wt/del) (P < 0.02). CCR5 (wt) mRNA expression in unstimulated PBMCs was significantly increased in wt/wt individuals compared to that of wt/del individuals (P < 0.01). In wt/del individuals, del CCR5 mRNA was expressed at 10-fold greater levels than wt CCR5 mRNA in unstimulated PBMCs from the same individual. Flow cytometry confirmed that upregulated CCR5 mRNA following type 1 cytokine stimulation leads to increased cell surface expression of CCR5 protein. The type 2 cytokine IL-10 downregulated both CCR5 mRNA and protein expression in wt/wt and wt/del individuals. Proinflammatory, type 1, and type 2 cytokines significantly increased CXCR4 mRNA expression in wt/wt, wt/del, and del/del CCR5 genotypes (P < 0.02). These results suggest that changes in the cytokine milieu influence chemokine receptor expression and may explain emergence of tropism-specific strains facilitating HIV transmission and disease progression.

Base Sequence↗