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Biomedical subjects

J X Wu

Publications and source records attributed to J X Wu.

At least 19 recordsLinked to original sources

The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer.

AIM: Serum tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and CA242 were investigated to evaluate the values of single and combined test in the diagnosis and prognosis of pancreatic cancer. METHODS: Pre-operative serum CEA, CA19-9 and CA242 were measured in 105 pancreatic cancers, 70 non-pancreatic malignancies and 30 benign pancreatic diseases. RESULTS: The sensitivity of CA19-9 alone was the highest in pancreatic cancer patients (80%), but the specificity was significantly lower than that of CEA and CA242 (P<0.01). The combination of CEA and CA242 could increase the specificity to 92%. In serum CA242 positive patients, the survival time was remarkably shorter than that of patients with negative result (P<0.01). The survival time in patients with more than two markers positive expression of CEA, CA19-9 and CA242 was obviously shorter than that of only one or no marker positive expression (P<0.05). CONCLUSION: The diagnostic rate of CA19-9 in pancreatic cancer is better than that of CEA and CA242. Combined detection of CEA and CA242 can improve the diagnostic specificity obviously. High levels of serum markers are associated with advanced stage of the disease. Patients with two or three markers positive expression of CEA, CA19-9, and CA242 simultaneously had a shorter survival time.

Adult↗

Mild conversion of alcohols to alkyl halides using halide-based ionic liquids at room temperature.

[reaction--see text] Alcohols were efficiently converted to alkyl halides using 1-n-butyl-3-methylylimidazolium halides (ionic liquids) in the presence of Brønsted acids at room temperature. The alkyl halide products were easily isolated from the reaction mixture via simple decantation or extraction, and the 1-n-butyl-3-methylimidazolium cation could be recycled for further uses.

Journal Article↗

Macrocyclization in the design of a conformationally constrained Grb2 SH2 domain inhibitor.

Grubbs' olefin metathesis reaction was utilized to prepare a macrocyclic variant of a linear Grb2 SH2 domain antagonist in an attempt to induce a beta-bend conformation known to be required for high affinity binding. In extracellular Grb2 SH2 domain binding assays, the macrocyclic analogue exhibited an approximate 100-fold enhancement in binding potency relative to its linear counterpart. The macrocycle was not as effective in whole cell binding assays as would be expected based on its extracellular binding potency.

Adaptor Proteins, Signal Transducing↗

N-terminal carboxyl and tetrazole-containing amides as adjuvants to Grb2 SH2 domain ligand binding.

High affinity binding of peptides to Src homology 2 (SH2) domains, often requires the presence of phosphotyrosyl (pTyr) or pTyr-mimicking moieties in the N-terminal position of the binding ligand. Several reports have shown that N(alpha)-acylation of the critical pTyr residue can result in increased SH2 domain binding potency. For Grb2 SH2 domains which recognize pTyr-Xxx-Asn-NH(2) motifs, significant potency enhancement can be incurred by N(alpha)-(3-amino)Z derivatization of tripeptides such as pTyr-Ile-Asn-NH(2). Using ligands based on the high affinity pY-Ac(6)c-Asn-(naphthylpropylamide) motif, (where Ac(6)c=1-aminocyclohexanecarboxylic acid), additional reports have shown moderate potentiating effects of N(alpha)-oxalyl derivatization. The current study examined variations of the N(alpha)-oxalyl theme in the context of a Xxx-Ac(6)c-Asn-(naphthylpropylamide) platform, where Xxx=the hydrolytically stable pTyr mimetics phosphonomethyl phenylalanine (Pmp) or carboxymethyl phenylalanine (Cmf). The effects of N(alpha)-(3-amino)Z derivatization were also investigated for this platform, to ascertain whether the large binding enhancement reported for tripeptides such as pTyr-Ile-Asn-NH(2) could be observed. In ELISA-based extracellular Grb2 SH2 domain binding assays, it was found for the Pmp-based series, that extending the oxalyl carboxyl out by one methylene unit or replacing carboxyl functionality with a tetrazole isostere, resulted in binding potency greater than the parent N(alpha)-acetyl-containing compound, with enhancement approximating that observed for the N(alpha)-oxalyl derivative. When Cmf was used as the pTyr mimetic, only modest differences in IC(50) values were observed for the series. Examination of the N(alpha)-(3-amino)Z derivatized Pmp-Ac(6)c-Asn-(naphthylpropylamide), showed that binding affinity was reduced relative to the parent N(alpha)-acetyl analogue, in contrast to the reported significant enhancement of affinity observed with other peptide ligands. Treatment of MDA-453 tumor cells, which are mitogenically driven through erbB-2 tyrosine kinase-dependent pathways, with Pmp-containing inhibitors resulted in growth inhibition, with the N(alpha)-oxalyl and N(alpha)-malonyl-containing compounds exhibiting IC(50) values (4.3 and 4.6 microM, respectively) approximately five-fold lower than the parent N(alpha)-acetyl-containing compound. Tetrazole and N(alpha)-(3-amino)Z-containing inhibitors were from two- to four-fold less potent than these latter analogues in the growth inhibition assays.

Adaptor Proteins, Signal Transducing↗

[Clinical characteristics of Parkinson's disease in natural population].

OBJECTIVE: To study the Clinical characteristics of Parkinson's disease(PD) in natural population. METHODS: All the patients diagnosed as Parkinsonism from a prevalence study in Beijing in 1997 were collected for investigation. The spectrum of the clinical features of Parkinsonism and the onset, progression and prognosis of PD were analysed, as well as the impact factors to the prognosis were analysed. RESULTS: 109 cases were ascertained as PD from the sample population, in which 64(58.7%) were PD, 11 (10.1%) were Parkinson plus syndrome and 34(31.2%) were symptom Parkinsonism. 30 of the 64 PD cases were male. The median age of PD was 74.5 years. The median age at onset was 68 years old. The median duration was 5 years. The average Hoehn-Yahr staging score was 2.81. The clinical characteristics of PD and other Parkinsonism were compared, as asymmetry of symptoms and signs was an important feature to differentiate PD from other Parkinsonism. 20.3 percent of PD cases were associated with dementia. 16(25%) of the 64 PD cases initiated with essential tremor and developed to PD during 6-49 years after the onset of tremor. Tremor was the dominant initial symptoms of PD(60.9%). Type of initial symptoms was a relatively definite impact factor to the prognosis of PD. Levodopa treatment was likely to delay the duration of PD. CONCLUSIONS: The clinical features of Parkinsonism in natural population were different as compared with previous studies. A further study on the natural history of PD thoroughly is needed.

Age of Onset↗

[Changes of glucocorticoid receptor in cerebral and hepatic cytosol during decompression stress injury in rats].

Objective. To observe the changes of glucocorticoid receptor (GR) in cerebral and hepatic cytosol during decompression stress injury in rats. Method. 30 rats were divided into 5 group. They were placed into the compression chamber for compression and decompression. The binding capacity of GR of cerebral and hepatic cytosol were measured by the exchange assay, using 3H dexamethasone as the ligand. Meanwhile, decompression bubbles on pericardial area were measured using Doppler ultrasonic method. Result. The binding capacity of GR of cerebral and hepatic cytosol reduced after decompression stress injury in the animals, especially cerebral cytosol (P<0.01, P<0.05). The result also showed that the binding capacity of cerebral and hepatic GR should have further decreased, if the therapeutic measure had not been used in animals suffered from decompression sickness (DCS). Conclusion. The changes of the binding capacity of GR of cerebral and hepatic cytosol were proved to be related to decompression stress injury, which might be taken as one of the indices for evaluating injury degree of DCS.

Animals↗

Preneoplastic mammary tumor markers: Cripto and Amphiregulin are overexpressed in hyperplastic stages of tumor progression in transgenic mice.

Amphiregulin (Ar) and Cripto (Cr) are autocrine growth factors for mammary cells and both have been observed to exhibit high expression in human mammary tumors, in contrast with adjacent tissues. To investigate whether Ar and Cr play roles in the progression of mammary cell proliferation to unregulated growth and tumor formation, the levels of expression were examined in transgenic mice (TGM) that over-express several different oncogenes: MMTV-Polyoma virus middle T antigen (MMTV-PyMT), MMTV-c-ErbB2 (c-neu, HER2) and MT-hTGF alpha. These transgenic mice all produce mammary tumors but with different rates of progression. The levels of Ar were induced up to 10-fold in association with hyperplasia in 2 of the TGM. Cr overexpression was consistently observed in hyperplastic mammary glands in all the animal models, decreasing in overt tumors in 2 of the TGM models. In MMTV-PyMT mammary glands, the levels of Cr expression rose 7- to 10-fold in hyperplastic tissue and 25-fold the levels in tumors compared to age-matched transgene negative mice. Ar and especially Cr thus should have potential value as markers of preneoplastic change in mammary tissue.

Amphiregulin↗

An AI approach to dynamic visual field testing.

Visual field test results are crucial to the accuracy and efficiency of diagnosing blinding diseases such as glaucoma. Herein, a method of integrating self-organizing neural networks and empirical heuristics is used to perform visual field tests via a dynamic test strategy, which can lead to a reduction in the number of trials in a perimetric test. Experiments performed using clinical test records show that we are able to reduce by 20% to 30% the number of trials per test without much adverse effect on the accuracy of the tests.

Algorithms↗

Frequency of asymmetric visual field defects in normal-tension and high-tension glaucoma.

OBJECTIVE: The purpose of the study was to evaluate the frequency of asymmetric visual field loss at presentation in patients with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG). DESIGN: A retrospective cross-sectional study design was used. PARTICIPANTS: Four hundred and three NTG patients and 337 consecutive HTG patients (consecutive diagnoses between 1986 and 1996). INTERVENTION: Analysis of the frequency of unilateral field loss presentations in NTG and HTG. The visual fields of fellow eyes were compared to determine the side of more severe field loss. For the NTG patients, the relationship between the side with greater field loss and corresponding intraocular pressure (IOP) was investigated. MAIN OUTCOME MEASURES: Humphrey field analyzer mean defect (MD) and mean diurnal IOP. RESULTS: In the NTG group, 101 (25%) patients presented with unilateral field loss. The proportion of cases with unilateral field loss decreased with increasing age of presentation (chi-square test for trend = 26.9; P < 0.0001). Sixty-four percent of the patients had unilateral field loss in the left eye. Sixty-eight percent of the cases with bilateral field loss had a higher MD in the left eye. The diurnal IOP was estimated as 0.23 +/- 0.068 mmHg (mean +/- SE) higher in the left eye (P = 0.001). In the HTG group, 104 (31%) patients presented with unilateral field loss. The proportion of cases with unilateral field loss decreased with increasing age of presentation (chi-square test for trend = 4.6; P = 0.03). Right and left eyes had an equal chance of having field loss in unilateral cases and of being the side of more advanced field damage in bilateral cases. CONCLUSIONS: The frequency of cases with unilateral field loss was similar in HTG and NTG patients. Patients with unilateral field loss at presentation were more likely to be at the younger end of the age range. In the NTG population we studied, the left eye was more frequently the side of onset of field loss and 2.1 times more likely to present with a greater field defect than the right eye. In HTG patients, right and left eyes showed an equal chance of being the side of onset of field damage and the more affected side.

Aged↗

Tumor necrosis factor alpha augments the expression of glucose-6-phosphate dehydrogenase in rat hepatic endothelial and Kupffer cells.

Cellular activity of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the hexose monophosphate shunt, supports several pathways involved in the nonspecific immune response. In the present study, we investigated the in vivo effects of selected pro-inflammatory cytokines on the expression of G6PD in Kupffer and hepatic endothelial cells. Murine recombinant TNF alpha, IL-1 beta, or IL-6 (1.5 x 10(5) U/kg) was injected and cellular G6PD mRNA level determined using a quantitative reverse transcription and polymerase chain reaction method. G6PD mRNA was elevated two- to threefold seven hours after the injection of TNF alpha in Kupffer and endothelial cells as compared to cells from saline-injected animals. The elevated G6PD mRNA was accompanied by increased cellular enzyme activity in both cells. The cellular activity of 6-phosphogluconate dehydrogenase (6PGD) was also increased seven hours after TNF alpha treatment in these cells. G6PD mRNA and enzyme activity returned to control levels 22h after TNF alpha administration. In contrast to the marked effects of TNF alpha, no significant alterations were found on G6PD expression following IL-1 beta or IL-6 injections in these cells. None of these cytokines caused changes in G6PD or 6PGD expression in parenchymal cells. These data indicate that the proinflammatory cytokine TNF alpha plays an important role in the regulation of cellular G6PD expression in hepatic immune competent cells.

Animals↗

Variation of nerve fibre layer thickness measurements with age and ethnicity by scanning laser polarimetry.

AIMS: Scanning laser polarimetry is a new technique allowing quantitative analysis of the retinal nerve fibre layer in vivo. This technique was employed to investigate the variation of the retinal nerve fibre layer thickness in a group of normal subjects of different ages and ethnic groups. METHODS: 150 normal volunteers of different ages and ethnic groups were recruited for this study. Three consecutive 15-degree polarimetric maps were acquired for each subjects. Nerve fibre layer thickness measurements were obtained at 1.5 disc diameters from the optic nerve. Four 90-degree quadrants were identified. RESULTS: The mean nerve fibre layer thickness varied from a minimum of 55.4 microns to a maximum of 105.3 microns, with a mean thickness value of 78.2 (SD 10.6) microns. Superior and inferior quadrants showed a comparatively thicker nerve fibre layer than nasal and temporal quadrants. Retinal nerve fibre layer thickness is inversely correlated with age (p < 0.001). White people showed thicker nerve fibre layers than Afro-Caribbeans (p = 0.002). CONCLUSION: The results indicate a progressive reduction of the nerve fibre layer thickness with increasing age. This may be due to a progressive loss of ganglion axons with age as suggested in postmortem studies. A racial difference in nerve fibre layer thickness is present between whites and Afro-Caribbeans.

Adolescent↗

Role of glutathione and catalase in H2O2 detoxification in LPS-activated hepatic endothelial and Kupffer cells.

The present study investigated the effect of lipopolysaccharide (LPS; from Escherichia coli, 2 mg/kg body wt ip) on selected aspects of the antioxidant status in Kupffer and sinusoidal endothelial cells. Cells were isolated 18 h after the injection of saline or LPS. In fresh suspension cultures, cellular reduced glutathione (GSH) and H2O2 were determined by monochlorobimane, and 2',7'-dichlorofluorescein diacetate, respectively, using a fluorescence plate reader. LPS injection increased GSH content two- to threefold in Kupffer cells compared with cells from control rats. Cellular GSH content was higher in endothelial than Kupffer cells. However, LPS did not increase GSH content in endothelial cells. Addition of H2O2 (40-200 microM) to Kupffer or endothelial cells caused a transient decrease in GSH, which was more pronounced in cells from control rats (approximately 45% drop) than in LPS-exposed cells (approximately 25% drop). Depleted GSH levels were accompanied by a proportional increase in cellular H2O2. After inhibition of catalase by 3-amino-1,2,4-triazole, the presence of 0.2 mM H2O2 depleted GSH content by 75% and 40% in Kupffer cells from saline- or LPS-injected rats, respectively. The same treatments caused a similar 50% decrease in both activated and control endothelial cells. LPS decreased catalase activity by 45% in Kupffer cells, whereas it had no effect on catalase in endothelial cells. Glutathione reductase activity was not altered by LPS in either cell type. These data show that in activated Kupffer cells the elevated level of cellular glutathione plays an augmented role in the protection against reactive oxygen species, whereas the contribution of catalase to H2O2 detoxification is attenuated. In LPS-stimulated endothelial and Kupffer cells, the efficient maintenance of GSH is consistent with upregulated production of reducing power through the hexose phosphate shunt observed previously.

Amitrole↗

Antinociceptive activities of 70% methanol extract of evodiae fructus (fruit of Evodia rutaecarpa var. bodinieri) and its alkaloidal components.

The effects of 70% methanol extract (EA-ext) from Evodiae Fructus (EA) consisting of dried fruits of Evodia rutaecarpa var. bodinieri (Rutaceae) on nociceptive responses were investigated. Oral administration of 50 or 200 mg/kg EA-ext had the same antinociceptive effect on writhing responses as induced by acetic acid. Its major alkaloidal constituents, evodiamine and rutaecarpine also had the antinociceptive effect. EA-ext significantly decreased the frequency of licking behavior within a unit of time at the late phase without affecting that of the early phase in the formalin test. EA-ext also increased nociceptive threshold of the inflamed paw without increasing that in the non-inflamed paw in the Randall-Selitto test. Although EA-ext inhibited the rise of vascular permeability induced by acetic acid and the increase of paw edema induced by carrageenin, it was ineffective on nociceptive response in the hot plate test and on locomotor activity. These results suggest that EA possesses antinociceptive effects and its mode of action may be mediated by anti-inflammatory action, and that the antinociceptive constituents are only partially attributable to alkaloidal components mentioned above.

Alkaloids↗

No correlation between side-chain of propranolol oxidation and S-mephenytoin 4'-hydroxylase activity.

AIM: To determine if any correlation between the side-chain oxidative capacity for propranolol and S-mephenytoin 4'-hydroxylase (cytochrome P-450 2C19, CYP2C19) activity in healthy Chinese of Han nationality. METHODS: S-mephenytoin oxidative metabolite 4'-hydroxymephenytoin (4'OH-M), S- and R-mephenytoin, and naphthoxyl-actic acid (NLA) excreted in urine, and propranolol in plasma were measured after 14 healthy extensive metabolizers of S-mephenytoin oxidation were given a single oral dose of racemic mephenytoin 100 mg and racemic propranolol 80 mg, respectively. S/R-mephenytoin in urine was determined by chiral capillary gas chromatography with nitrogen-phosphorus detection, 4'-OH-M in urine by reversed-phase liquid chromatography (RPLC) with ultraviolet detection, and plasma propranolol or urinary NLA by the RPLC with fluorescence detection. RESULTS: No significant correlations were found between the partial metabolic clearance (Clm) of propranolol to NLA and 8 h urinary S/R ratio of mephenytoin (rs = -0.0484; P = 0.8695), nor between the Clm and log10 of 8 h urinary excretion of 4'-OH-M (rs = -0.1077; P = 0.7140). CONCLUSIONS: CYP2C19 is not a principal P-450 isozyme responsible for the in vivo side-chain oxidation of propranolol in the Chinese.

Aryl Hydrocarbon Hydroxylases↗

[Effects and mechanism of emodin and sandostatin on pancreatic ischemia in acute haemorrhagic necrotizing pancreatitis].

OBJECTIVE: To investigate pancreatic ischemia and abnormal metabolism of eicosanoids in acute haemorrhagic-necrotizing pancreatits (AHNP) and the effects of emodin or sandostatin on them. METHODS: Rats with AHNP were triggered with sodium taurocholate; the pancreatic blood flow (PBF) was detected with computerized tissue blood flowmeter, and plasma prostaglandin E2 (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane (TXB2) were determined with radioimmunoassay. RESULTS: There was a significant decrease of PBF in the early stage of AHNP. Compared with that in the untreated group, significant improvement of PBF was demonstrated in emodin as well as in sandostatin group which showed reduced PBF following infusion of sandostatin before triggering AHNP. In untreated group plasma TXB was significantly higher, with an increase of 4.5 times, than that in sham-operated group while 6-keto-PGF1 alpha or PGE2 tended to decrease. The above mentioned abnormal synthesis of eicosanoids was blocked either in emodin or in sandostatin group in which lessened damage of acini cells was shown by pathologic scoring or transmission electron microscope. Both of the two groups shared significantly lower mortalities than the untreated group. CONCLUSION: Either emodion or sandostatin could partly reverse the decrease of PBF in the early stage of AHNP, which may be ascribed at least in part to inhibition of abnormal synthesis of eicosanoids and improvement of cytoprotection of acini cells, and combined application of the two drugs might promise positively synergetic action as well.

6-Ketoprostaglandin F1 alpha↗

Modifications in lens protein biosynthesis signal the initiation of cataracts induced by buthionine sulfoximine in mice.

Cataract induction in preweanling mice by L-buthionine sulfoximine (BSO), an inhibitor of glutathione biosynthesis, was correlated with perturbations in vitro protein biosynthesis. These were detected by incubation of late precataract and early cataract lenses with 35S-labeled amino acids, followed by dissection of lenses into capsule-epithelium and decapsulated fiber fractions, further processing of the fibers into water-soluble, urea-soluble and urea-insoluble fractions, and analysis by 2D electrophoresis and fluorography. Most of the protein labeling in control lenses was in the water-soluble fiber and capsule-epithelium fractions (80% and 14% of total cpm, respectively). Labeling in all three fiber fractions was decreased by cataract induction. The urea-insoluble fraction displayed a transient increase in labeled high molecular weight basic protein, as labeling of polypeptide monomers decreased. Densitometric analysis of fluorograms from the water-soluble and urea-soluble fiber fractions revealed a sharp decrease in fiber gamma-crystallin polypeptide labeling preceding and accompanying early cataract development, a delayed decrease in labeling of alpha A-crystallin and increased relative percentage of several labeled beta-crystallin polypeptides, especially in the urea-soluble fraction. By contrast with diminished labeling of the fiber fractions during cataract initiation, protein labeling of the corresponding capsule-epithelium fraction was stimulated dramatically and persisted at reduced levels during early opacification (stage 3), when nearly all of the protein labeling in the lens was found in capsule-epithelium. Capsule-epithelium polypeptides showing increased labeling during cataract initiation included alpha A-crystallin, several acidic polypeptides of M(r) = 40-50 kDa and a group of neutral to mildly acidic polypeptides of M(r) = 20-28 kDa. this transient activation, which was relatively non-specific, may relate to previously reported observations of polyribosome accumulation in lens epithelium during initial development of BSO cataracts. The labeled capsule-epithelium preparations are known to include newly differentiating fibers near the lens equator as well as epithelial cells. Both of these cell populations survive in mature BSO cataracts. It is suggested that modifications of the normal pattern of gene expression in the lens may be involved in initiation of the mouse BSO cataract and its subsequent pattern of development.

Animals↗