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Biomedical subjects

F H Wang

Publications and source records attributed to F H Wang.

At least 19 recordsLinked to original sources
PubMed2006

The electrochemical corrosion of bulk nanocrystalline ingot iron in acidic sulfate solution.

The corrosion properties of bulk nanocrystalline ingot iron (BNII) fabricated from conventional polycrystalline ingot iron (CPII) by severe rolling were investigated by means of immersion test, potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS) tests, and scanning electron microscopy (SEM) observation. These experimental results indicate that BNII possesses excellent corrosion resistance in comparison with CPII in acidic sulfate solution at room temperature. It may mainly result from different surface microstructures between CPII and BNII. However, the corrosion resistance of nanocrystalline materials is usually degraded because of their metastable microstructure nature, and the residual stress in nanocrystalline materials also can result in degradation of corrosion resistance according to the traditional point of view.

Journal Article↗
PubMed2005

Preparation and electrochemical corrosion behavior of bulk nanocrystalline ingot iron in HCl acid solution.

Bulk nanocrystalline ingot iron (BNII) was produced by the severe rolling technique. The corrosion behaviors of BNII and as-received conventional polycrystalline ingot iron (CPII) in 1 M HCl solution were investigated by potentiodynamic polarization tests, electrochemical impedance spectroscopy measurement, and immersion tests at room temperature. For BNII, the anodic dissolution process is inhibited, but the cathodic process is enhanced. The corrosion current and average corrosion rate of BNII are 0.479 and 0.391 those of CPII, respectively. The resistance of the charge transfer of BNII is about 1.59 times higher than that of CPII. These results indicate that the corrosion resistance of BNII is improved in comparison with CPII.

Journal Article↗
PubMed2001

Microdialysis in freely moving mice: determination of acetylcholine, serotonin and noradrenaline release in galanin transgenic mice.

In the present study, we describe micro-surgical methods for simultaneous implantation of a microdialysis probe and an intraventricular injection cannula via their respective guide cannulas into the mouse brain. Basal and stimulated release of acetylcholine (ACh), serotonin (5-HT) and noradrenaline (NA) was determined in the ventral hippocampus of freely moving mice. NA and 5-HT were determined in one run by a newly developed HPLC method based on precolumn derivatization with benzylamine and fluorescence detection. The mice with a loss-of-function mutation of the galanin gene (KO) and the mice that over-expressed galanin (OE) were studied. No significant differences in basal, potassium-stimulated or scopolamine-induced extracellular ACh levels were observed in 4-month-old wild-type (WT) and KO mice. In the aged, 10-month-old animals, the basal extracellular ACh levels were significantly reduced in both WT and KO groups. Galanin (1 nmol i.c.v.) caused a significant reduction of basal extracellular NA by about 40% in both WT and galanin OE mice, however, in the latter group the effect was delayed by almost 2 h. A 10-min forced swimming stress caused a higher increase in release of NA and 5-HT in the OE group than in the corresponding WT mice. Finally, venlafaxin (10 mg/kg i.p.) increased extracellular NA to 400% of the control values in the CBA mice, but only to 250% in the C57BL mice. It is concluded that galanin may play an important role in the cholinergic mechanisms underlying cognitive disorders. Furthermore, modulation by galanin and by behavioral activation, of NA and 5-HT neurotransmission in galanin over-expressing mice indicates its possible role in the aetiology of mood disorders.

Acetylcholine↗
PubMed2001

Prolonged effects of intraventricular galanin on a 5-hydroxytryptamine(1A) receptor mediated function in the rat.

Galanin (3 nmol/rat), 2 h after its intracerebroventricular (i.c.v.) administration to male rats, attenuated the passive avoidance (PA) retention deficit induced by the 5-hydroxytryptamine (HT)(1A) receptor agonist 8-hydroxy-2-(di-N-propylamino)tetraline (8-OH-DPAT) (0.2 mg/kg) The reduction in the postjunctional 5-HT(1A) receptor-mediated response after i.c.v. galanin was not associated with changes in the mRNA levels and agonist binding properties of cortical limbic 5-HT(1A) receptors, believed to be the target receptors mediating the PA deficit caused by 8-OH-DPAT. These results suggest that acute increases of galanin transmission in vivo even after 2 h can counteract limbic 5-HT(1A) receptor-mediated responses of relevance for affective disorders without significantly affecting gene expression and binding characteristics of cortical limbic 5-HT(1A) receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Interleukin-10-induced T cell unresponsiveness can be reversed by dendritic cell stimulation.

The secretion of immunosuppressive factors like interleukin-10 (IL-10), either by tumor cells or by tumor-infiltrating leukocytes, has been recognized as one of the mechanisms involved in tumor immunological escape and a serious obstacle for successful immunotherapy. Therefore, any therapeutic attempts aimed at inducing antitumor immunity in tumor-bearing hosts must overcome this immunosuppressive state. This study aimed to determine whether dendritic cell (DC) immunization, a promising approach to induce antitumor immunity, could break IL-10-induced anergic state in CD4+ T cells, essential cells in generating tumor-specific immunity. We found that the ability of DC to reverse IL-10-induced anergic state in human CD4+ T cells is dependent on the IL-10 concentration that T cells have been exposed to and the degree of DC maturation. The efficacy of mature DC in reversing T cell anergy can be mimicked by higher cell numbers of immature DC. In addition, activated T cells induced by DC stimulation are sensitive to IL-10 treatment. Collectively, our results suggest the use of mature DC and the necessity of antagonizing the action of tumor-derived IL-10 in immunotherapy of cancer with DC immunization.

CD4-Positive T-Lymphocytes↗
PubMed2000

Galanin regulates the postnatal survival of a subset of basal forebrain cholinergic neurons.

The neuropeptide galanin colocalizes with choline acetyltransferase, the synthetic enzyme for acetylcholine, in a subset of cholinergic neurons in the basal forebrain of rodents. Chronic intracerebroventricular infusion of nerve growth factor induces a 3- to 4-fold increase in galanin gene expression in these neurons. Here we report the loss of a third of cholinergic neurons in the medial septum and vertical limb diagonal band of the basal forebrain of adult mice carrying a targeted loss-of-function mutation in the galanin gene. These deficits are associated with a 2-fold increase in the number of apoptotic cells in the forebrain at postnatal day seven. This loss is associated with marked age-dependent deficits in stimulated acetylcholine release, performance in the Morris water maze, and induction of long-term potentiation in the CA1 region of the hippocampus. These data provide unexpected evidence that galanin plays a trophic role to regulate the development and function of a subset of septohippocampal cholinergic neurons.

Animals↗
PubMed1999

Molecular cloning and characterization of a mouse homolog of bacterial ClpX, a novel mammalian class II member of the Hsp100/Clp chaperone family.

In this paper, we present the molecular cloning and characterization of a murine homolog of the Escherichia coli chaperone ClpX. Murine ClpX shares 38% amino acid sequence identity with the E. coli homolog and is a novel member of the Hsp100/Clp family of molecular chaperones. ClpX localizes to human chromosome 15q22.2-22.3 and in mouse is expressed tissue-specifically as one transcript of approximately 2.9 kilobases (kb) predominantly within the liver and as two isoforms of approximately 2.6 and approximately 2.9 kb within the testes. Purified recombinant ClpX displays intrinsic ATPase activity, with a Km of approximately 25 microM and a Vmax of approximately 660 pmol min-1 microgram-1, which is active over a broad range of pH, temperature, ethanol, and salt parameters. Substitution of lysine 300 with alanine in the ATPase domain P-loop abolishes both ATP hydrolysis and binding. Recombinant ClpX can also interact with its putative partner protease subunit ClpP in overexpression experiments in 293T cells. Subcellular studies by confocal laser scanning microscopy localized murine ClpX green fluorescent protein fusions to the mitochondria. Deletion of the N-terminal mitochondrial targeting sequence abolished mitochondrial compartmentalization. Our results thus suggest that murine ClpX acts as a tissue-specific mammalian mitochondrial chaperone that may play a role in mitochondrial protein homeostasis.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1999

Ionizing radiation stimulates octamer factor DNA binding activity in human carcinoma cells.

In mammalian cells, the octamer motif (ATGCAAAT) binding proteins, Oct-1 and Oct-2, play an important role in the transcriptional transactivation of several ubiquitously expressed genes as well as cell-specifically expressed genes. To date, a role of the octamer binding proteins in damage-stimulated response is not known. In this report, we demonstrate that DNA-binding activity of Oct-1, as demonstrated by the electrophoretic mobility shift assay, is significantly induced in a dose-dependent manner upon treatment of human head and neck squamous carcinoma cells (PCI-04A) with ionizing radiation (5 Gy: 5-fold; 15 Gy: 11-fold). By comparison, activities of other transcription factors were modestly increased (15 Gy: AP-1, 2.5-fold; NF-kappaB, 2.6-fold; SP-1, 5-fold). Radiation stimulation of Oct-1 activity was also noted in two other human cancer cell lines, albeit to a lesser extent (MDA-MB231 breast carcinoma cells and PC-3 prostate carcinoma cells (5 Gy: approximately 2-fold). These data represent the first report of the activation of an octamer factor DNA binding activity in response to environmental cues and suggest a novel role of Oct-1 in the radiation signaling cascade in these cancer cells.

Carcinoma, Squamous Cell↗
PubMed1998

Galanin modulates 5-hydroxytryptamine functions. Focus on galanin and galanin fragment/5-hydroxytryptamine1A receptor interactions in the brain.

The reciprocal interactions between galanin and 5-HT1A receptors in the rat brain are presented. Galanin and its NH2-terminal fragments antagonize 5-HT1A receptor-mediated transmission at the postjunctional level, whereas galanin receptor activation mimics the inhibitory action of 5-HT1A receptor activation at the soma-dendritic level, leading to reductions of 5-HT metabolism and release. These interactions have been shown in both receptor binding studies and functional studies. In view of the present findings, galanin antagonists may represent a new type of anti-depressant drug, based on the 5-HT hypothesis of depression, by enhancing 5-HT release and postjunctional 5-HT1A-mediated transmission. Moreover, following intracerebroventricular injection galanin was found to be internalized in a population of hippocampal nerve cells mainly representing GABA, somatostatin, and/or NPY-immunoreactive nerve cells. The relevance of these findings is discussed in relation to the concept of volume transmission.

Animals↗
PubMed1998

Ursodeoxycholic acid increased bile flow and affects bile composition in the early postoperative phase following liver transplantation.

Orally given ursodeoxycholic acid (UDCA) has beneficial effects on laboratory parameters in different cholestatic conditions. In order to investigate the effect on early graft function after liver transplantation, 33 patients were randomized to receive either UDCA 15 mg/kg per day or placebo from the 1st postoperative day until 3 months after transplantation. All liver grafts produced bile within 24 h after revascularization. In both groups there was an increasing bile flow each day until day 5 after transplantation. This increase was more pronounced in the UDCA group where the flow on day 2 reached a mean value of 183 +/- 28 ml/day compared to 106 +/- 17 ml/day in the placebo group (P < 0.05). The average daily volume of bile produced during the first 10 days was also found to be higher in the UDCA group compared to the placebo group (242 +/- 20 ml vs 176 +/- 18 ml, P < 0.02). In the UDCA group a significant decrease in total bile acid output between the 5th and 10th postoperative days was found, while in the placebo group the amount of bile acids excreted remained stable over time. The composition of bile differed between the two groups with an increase in the portion of UDCA in the UDCA group from the 2nd postoperative day (25% vs 4.6%, P < 0.0003). The fraction of UDCA then remained high during the whole study period with a peak at day 3 when 38.1 +/- 6.6% of the bile acids consisted of UDCA. In the placebo group, the fraction of UDCA was low from the beginning and diminished further over time. Prophylactic UDCA treatment was found to have a significant positive impact on the ALT level during the 4th and 5th postoperative days, but had no effect on bilirubin or GGT in the early postoperative phase (days 1-10). No differences in cyclosporine requirement were found between the two groups.

Adult↗
PubMed1998

Effects of short-term treatment with pravastatin on the hepatic synthesis of cholesterol and bile acids in gallstone patients.

BACKGROUND: HMG-CoA reductase inhibitors are now the therapy of choice in the treatment of hypercholesterolaemia. The effects of long-term treatment with these substances on plasma lipoproteins, cholesterol metabolism and biliary secretion of lipids have been extensively studied in humans. Much less is known about the effects of short-term treatment. The aim of this study was to determine the time course of the effects of HMG-CoA reductase inhibitors on plasma lipoprotein levels as well as cholesterol and bile acid synthesis in gallstone patients. METHODS: Thirty-six patients undergoing elective cholecystectomy were included in the study. Except for the gallstone disease, these patients were otherwise healthy. Four groups of subjects were treated with the HMG-CoA reductase inhibitor pravastatin (Pravachol), 20 mg twice daily for 12, 24, 48 and 72 h preoperatively. Plasma lipoproteins and plasma levels of lathosterol and 7 alpha-hydroxy-4-cholesten-3-one were determined before initiation of pravastatin treatment and on the morning of the day of the operation, lathosterol reflecting hepatic HMG-CoA reductase activity and 7 alpha-hydroxy-4-cholesten-3-one the activity of cholesterol 7 alpha-hydroxylase, the rate-determining enzyme in bile acid synthesis. RESULTS: All treatment groups displayed a significant decrease in total cholesterol and low-density lipoprotein (LDL)-cholesterol, by about 12% and 17% respectively. Lathosterol was reduced by about 50% in all treatment groups. Of great interest was the finding that 7 alpha-hydroxy-4-cholesten-3-one was unaffected in all treatment groups. CONCLUSION: The results show that short-term pravastatin treatment in gallstone patients rapidly inhibits cholesterol synthesis and lowers plasma LDL-cholesterol levels without effects on bile acid synthesis.

Adult↗
PubMed1998

Intraventricular galanin modulates a 5-HT1A receptor-mediated behavioural response in the rat.

The present studies have examined whether the neuropeptide galanin can modulate brain serotoninergic (5-HT) neurotransmission in vivo and, particularly, 5-HT1A receptor-mediated transmission. For that purpose, we studied the ability of galanin (given bilaterally into the lateral ventricle, i.c.v.) to modify the impairment of passive avoidance retention induced by the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propyloamino)tetralin (8-OH-DPAT) when injected prior to training. This impairment appears to be mainly related to activation of 5-HT1A receptors in the CNS. Galanin dose-dependently (significant at 3.0 nmol/rat) attenuated the passive avoidance impairment (examined 24 h after training) induced by the 0.2 mg/kg dose of 8-OH-DPAT. This 8-OH-DPAT dose produced signs of the 5-HT syndrome indicating a postsynaptic 5-HT1A receptor activation. Furthermore, both the impairment of passive avoidance and the 5-HT syndrome were completely blocked by the 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg). Galanin (0.3 or 3.0 nmol) or WAY 100635 (0.1 mg/kg) failed by themselves to affect passive avoidance retention. 8-OH-DPAT given at a low dose 0.03 mg/kg, which presumably stimulates somatodendritic 5-HT1A autoreceptors in vivo, did not alter passive avoidance retention or induce any visually detectable signs of the 5-HT syndrome. Galanin (0.3 or 3.0 nmol) given i.c.v. in combination with the 0.03 mg/kg dose of 8-OH-DPAT, did not modify passive avoidance. The immunohistochemical study of the distribution of i.c.v. administered galanin (10 min after infusion) showed a strong diffuse labelling in the periventricular zone (100-200 microm) of the lateral ventricle. Furthermore, in the dorsal and ventral hippocampus galanin-immunoreactive nerve cells appeared both in the dentate gyrus and the CA1, CA2 and CA3 layers of the hippocampus. In the septum only endogenous fibres could be seen while in the caudal amygdala also galanin-immunoreactive nerve cells were visualized far away from the labelled periventricular zone. At the level of the dorsal raphe nucleus a thin periventricular zone of galanin immunoreactivity was seen but no labelling of cells. These results suggest that galanin can modulate postsynaptic 5-HT1A receptor transmission in vivo in discrete cell populations in forebrain regions such as the dorsal and ventral hippocampus and parts of the amygdala. The indication that galanin administered intracerebroventrically may be taken up in certain populations of nerve terminals in the periventricular zone for retrograde transport suggests that this peptide may also affect intracellular events.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Ionizing radiation and TNF-alpha and stimulated expression of alpha1-antichymotrypsin gene in human squamous carcinoma cells.

Alpha-1 antichymotrypsin (ACT), a serine protease inhibitor, has been detected in several epithelial tumor cell types, but its role in response to therapy is not clear. We report here that exposure of primary head and neck squamous cell carcinoma (HNSCC)-derived cells (PCI-04A) to ionizing radiation (IR) or tumor necrosis factor-alpha (TNF-alpha) resulted in an increased level of ACT mRNA, although the induction patterns were different. IR treatment caused a transient stimulation of ACT mRNA, peaking at 3 h post-irradiation, whereas TNF-alpha-inducible ACT gene expression lasted for up to 24 h. The ACT mRNA was expressed in several epithelial and non-epithelial tumor cell types, and in different normal human tissues. In addition, when the ACT gene expression in PCI-04A cells was compared with the matched (from the same patient) metastatic HNSCC-derived cells (PCI-04B), increased steady-state level of the ACT mRNA was observed in PCI-04B cells. Taken together, these findings suggest that ACT may serve as an important marker for prognosis and therapy selection in HNSCC.

Carcinoma, Squamous Cell↗
PubMed1997

Circulating markers for biosynthesis of cholesterol and bile acids are not depressed in asymptomatic gallstone subjects.

BACKGROUND/AIMS: Cholesterol gallstone disease is often associated with an increased biliary secretion rate of cholesterol, which may be due to abnormalities in hepatic cholesterol metabolism. The aim of the present study was to investigate whether gallstone subjects may have an underlying defect in hepatic cholesterol and bile acid formation. METHODS: In 41 asymptomatic gallstone subjects, randomly selected from a population of both sexes 40 and 60 years of age, and in 72 age- and sex-matched controls, plasma levels of lathosterol (reflecting hepatic HMG CoA reductase activity) and 7alpha-hydroxy-4-cholesten-3-one (reflecting cholesterol 7alpha-hydroxylase activity) were analysed. In a subgroup of gallstone subjects and controls, plasma levels of 27-hydroxy cholesterol were also determined. RESULTS: The gallstone subjects had normal plasma levels of cholesterol but displayed 20-25% higher plasma levels of triglycerides compared with the controls. The plasma level of lathosterol was not significantly different between the two groups of subjects whereas the plasma level of 7alpha-hydroxy-4-cholesten-3-one was about 40% higher in the gallstone subjects compared with the controls. Positive correlations were obtained between plasma levels of 7alpha-hydroxy-4-cholesten-3-one and triglycerides in both groups of subjects. The plasma level of 27-hydroxy cholesterol was similar in gallstone subjects and controls. CONCLUSIONS: The previously reported hypersecretion of cholesterol in gallstone patients is not due to a single metabolic defect leading to increased hepatic synthesis of cholesterol or decreased catabolism of cholesterol to bile acids via 7alpha-hydroxylation or 27-hydroxylation of cholesterol.

Adult↗
PubMed1997

Identification of seven differentially displayed transcripts in human primary and matched metastatic head and neck squamous cell carcinoma cell lines: implications in metastasis and/or radiation response.

The patterns of differential gene expression were examined in two primary (A's) and two matched-metastatic (B's) head and neck squamous cell carcinoma (HNSCC) cell lines by differential display of mRNAs and northern blot hybridisation. Three cell lines used (PCI-04A, PCI-04B and PCI-06A) were established independently prior to therapy, whereas one cell line (PCI-06B) was established from a recurrent tumor after radiation therapy. A total of seven differentially displayed mRNA clones were identified, of which six clones were obtained by comparison of PCI-06A cells with PCI-06B cells (SCC-S1a/b, SCC-1c, and SCC-S2, PCI-06B; SCC-S3 to SCC-S5, PCI-06A), and one clone was obtained from the PCI-04A and PCI-04B match (SCC-Sa, PCI-04B). Based on the DNA database search for homology to the known sequences, six of the seven partial cDNA clones (SCC-S1a/b, SCC-1c, SCC-S2 to SCC-S4, and SCC-Sa may represent novel genes, whereas one cDNA clone (SCC-S5) shows significant homology to the HLA class II antigen gene (DPW2 beta chain). Each of the seven clones revealed preferential expression by northern blotting in the cell line of origin as compared to the matched counterpart. The transcripts ranged in size from approximately 7.0 Kb to 0.5 Kb. Interestingly, the SCC-Sa clone was preferentially expressed in both metastatic cell lines compared to the primary tumour-derived cell lines. We conclude that the SCC-Sa gene may be more commonly involved in tumour metastasis, whereas expression of the other genes (SCC-S1a/b, SCC-S1c, SCC-S2-SCC-S5) may be associated with metastasis and/or response of HNSCC to ionising radiation.

Base Sequence↗
PubMed1997

Antisense raf oligodeoxyribonucleotide is protected by liposomal encapsulation and inhibits Raf-1 protein expression in vitro and in vivo: implication for gene therapy of radioresistant cancer.

We have redesigned cationic liposomes by using a combination of dimethyldioctadecyl ammonium bromide, phosphatidylcholine and cholesterol to enhance the in vitro and in vivo effectiveness of antisense raf oligodeoxyribonucleotide (ODN). Circulating ODNs carried in vivo by liposomes were intact for at least 24 h, while free ODNs were undetectable after 5 min. Liposome-encapsulated antisense raf ODN (LE-ATG-AS) inhibited Raf-1 protein expression in vitro and in vivo. Furthermore, radioresistant tumor cells treated with LE-ATG-AS raf ODN were sensitized to ionizing radiation. These data provide new information for the delivery and potency of antisense ODN in vivo, and support the use of LE-ATG-AS raf ODN for gene therapy of radioresistant cancer.

Animals↗
PubMed1997

The effect of vitamin C in high doses on plasma and biliary lipid composition in patients with cholesterol gallstones: prolongation of the nucleation time.

Vitamin C deficiency in guinea pigs leads to cholesterol supersaturation of bile and formation of cholesterol gallstones. It has been suggested that there may also exist an association between vitamin C and cholesterol gallstones in man, but such a relationship has not been studied in gallstone patients. In order to study the possible effects of vitamin C on gallstone disease in humans, plasma lipid levels, hepatic cholesterol metabolism, biliary lipid composition, cholesterol saturation and nucleation time of gallbladder bile were analysed in 16 consecutive gallstone patients, who were planned for laparoscopic cholecystectomy and were treated with vitamin C (500 mg, four times a day) for 2 weeks before surgery. The plasma concentration of vitamin C increased by 42% in the treatment group. The concentrations of plasma lipids did not differ before and after vitamin C treatment; nor did the plasma levels of lathosterol and 7 alpha-hydroxy-4-cholesten-3-one, reflecting cholesterol and bile acid synthesis respectively. The relative concentrations of cholesterol, bile acids and cholesterol concentration of bile did not differ significantly between the two groups, but the relative concentration of phospholipids was slightly higher in the treated group. The bile acid composition was changed; the percentage of cholic acid being lower and those of deoxycholic acid, ursodeoxycholic acid and lithocholic acid higher in the vitamin C-treated patients compared with the untreated group. The nucleation time was significantly longer in the treatment group (7 days) compared with the untreated group (2 days). Our findings indicate that vitamin C supplementation may also influence the conditions for cholesterol gallstone formation in humans.

Ascorbic Acid↗