Biomedical subjects

X Xu

Publications and source records attributed to X Xu.

At least 703 records · Page 39Linked to original sources

PubMed1997

[Study on the treatment and prognosis of lymphoplasmacytoid lymphoma: a report of 41 cases].

OBJECTIVE: To analyze the prognosis of lymphoplasmacytoid lymphoma. METHODS: The prognosis of 41 cases of lymphoplasmacytoid lymphoma in long-term follow-up were analyzed. RESULTS: The median survival was 39.4 months. The survival durations were significantly shorter in patients in clinical stage III , IV (P < 0.01), with B-symptoms (P < 0.05), and with bone marrow and extranodal involvements (P < 0.01). The tumor-free survival in patients received comprehensive treatment was longer than in those received chemotherapy alone (P < 0.05), but the overall survival durations between the two groups had no difference. CONCLUSION: No therapeutic benefit was obtained from actively overtreatment for lymphoplasmacytoid lymphoma.

Adolescent↗

PubMed1997

[Identification of photoproducts for PCB congeners by the new retention index system].

Polychlorinated biphenyls (PCBs) are a kind of priority pollutants, constituting a complex group of 209 congeners ranging from monochloro to decachlorobiphenyls. Because of the shortcomings of retention time data and the lack of suitable retention index systems, the congeners analysis of PCBs is one of the most challenging tasks in capillary column gas chromatography (GC), especially due to the fact that the isomers of PCBs can not be identified by GC-MS. A new retention index system, suitable for analysis of PCB congeners in the environmental samples by temperature-programmed capillary gas chromatography with ECD, has been developed recently by Chu et al. In this paper, retention indexes of all 209 PCB congeners were calculated according to the new retention index system from their respective retention times reported by other authors. The photoproducts of PCB87, PCB138 and PCB169 were identified with the new retention index system and confirmed by GC-MS. The deviations of retention indexes for all photoproducts were within 3 index units. It was testified that the above retention index system was reliable during the identification of PCB congeners and would have wide applicability. Based on the formations of coplanar PCB congeners (PCB77 and PCB126) during the photodegradations of PCB138 and PCB169, it was proposed that toxic equivalence (TEQ) should be used as a kind of quality indicator for the studies of the photolysis of PCBs.

Chromatography, Gas↗

PubMed1997

[Determination of aniline derivatives in waste water with reversed-phase high performance liquid chromatography].

A reversed-phase high performance liquid chromatographic method for the determination of aniline derivatives in waste-water is described. Chromatographic conditions were: column, Hypersil BDS (200 mm x 4.0 mm i.d., 5 microm); mobile phase, methanol-water, gradient elution; flow rate, 1.0 mL/min; detection wavelength, 254 nm. Quantification was carried out based on the external standard of aniline derivatives. The pH of waste water sample was adjusted to 11-12 with dilute NaOH solution prior to extraction with CH2Cl2. The extractives concentrated in K-D concentrator and filtered with FH 0.5 microm membrane. Finally make up the volume to 1 mL and test it with reversed-phase high performance liquid chromatography. The linearity range of calibration curve used was 0.005-0.3 microg. The minimum detectable quantities of aniline derivatives varied from 1.20 ng to 3.00 ng. The average recoveries were from 51.57% to 107.92%, and the RSDs of the method were from 1.88% to 5.98%. The method is simple, rapid, and accurate.

Aniline Compounds↗

PubMed1997

[Determination of degradation level of antifungal agent in mice serum by high performance liquid chromatography].

L-4-oxalysinyl-norvalinyl-N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid (I-677-Nva-FMDP) is a new tripeptide synthesized in our group. This peptide exhibits potent anticandida Albicans activity. In the presence of serum, the antifun gal activity of I-677-Nva-FMDP decreases after incubating over 1h. In order to investigate the relationship between the degradation and antifungal activity of I-677-Nva-FMDP, the concentrations of I-677-Nva-FMDP and N3-methoxyfumaroyl-L-2,3-diaminopropanoic acid (FMDP) were determined at different incubating time in mice serum. The incubating time range was from 0 to 300 min and the incubating samples were measured at intervals of 30 min. For this measurement reversed-phase HPLC was used and the mobile phase was composed of 8% methanol and 0.1% trifluoroacitic acid-triethyl amine buffer (pH 3). In this condition the retention time of FMDP and I-677-Nva-FMDP were 3.9 min and 16.5 min respectively. Methanol was superior to other reagents for the removal of protein from the incubating medium and there was not any interference peak before the retention time of I-677-Nva-FMDP. A decrease in concentration of I-677-Nva-FMDP was observed from 0 min to 180 min and no I-677-Nva-FMDP could be detected at 210 min whereas the concentration of FMDP incresed from 30 min to 2h and reached a maximum at 120 min. The results showed that the half life (t1/2) of I-677-Nva-FMDP was 70 min. This result coincided with the antifungal test in vitro.

Animals↗

PubMed1997

A hot spot for p53 mutation in transitional cell carcinoma of the bladder: clues to the etiology of bladder cancer.

Twenty-eight transitional cell carcinomas of the bladder, grade 2 or 3, were analyzed for the presence of p53 mutations. Thirteen tumors were found to contain 14 mutations. These were all base substitution mutations, of which nine were GC-->AT transitions (three at CpG sites). The remaining five mutations were transversions (three GC-->CG, one GC-->TA, and one AT-->TA). Four of the mutations were found at codon 280. A comparison with other studies of bladder tumors reveals that a region encompassing codons 280 and 285 represents a hot spot for p53 mutation in bladder cancer. The 280/285 hot spot lies within two purine-rich sequences that may provide some clues to the identity of potential bladder carcinogens. A comparison of mutations from bladder tumors of smokers and nonsmokers reveals no significant differences.

Adult↗

PubMed1997

Heterogeneity of androgen receptor content in advanced prostate cancer.

The principal mode of treatment of advanced (late stage) prostate cancer is androgen ablation. Although the response rate to hormonal ablation is high, relapse ultimately leading to death occurs in the majority of patients in remission from outgrowth of androgen-independent tumor cells. High-grade and high-stage cancers are more likely to progress to androgen independence. This study was undertaken to analyze the expression level of androgen receptor (AR) protein in prostatic carcinomas in relationship to grade and stage of disease. AR protein expression was assessed in 40 archival cases of prostate carcinoma by automated immunohistochemical techniques with standardized development times. Positive nuclei were quantitated by computer-assisted image analysis. Eighty-five percent of the prostatic carcinomas showed high levels of expression, defined as having AR present in more than 50% of the cells by light microscopy. Results of image analysis demonstrated that the variability of AR protein content per unit nuclear area increased with increasing grade (P < .03), regardless of cell size. High-grade prostatic intraepithelial neoplasia (PIN), present in 17 (42.5%) of the 40 cases, showed markedly reduced AR nuclear staining, compared with low-grade PIN or normal prostate. We show that AR content in prostate tumor cells becomes more variable with increasing Gleason score. In high-grade PIN, the in situ precursor of invasive prostate cancer, AR expression is either downregulated and/or restricted to the cytoplasm, but it is not heterogeneous. These data suggest that the heterogeneity in the expression of the receptor increases with progression of invasive prostate cancer and might in part account for a variable response to endocrine therapy.

Adult↗

PubMed1997

Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans.

Montelukast (L-706,631, MK-0476, SINGULAIR), a potent and selective leukotriene D4 (CysLT1) receptor antagonist, is currently under development for the treatment of asthma. In vitro studies were conducted using human liver microsomes to evaluate: 1) the difference in the metabolic kinetics of montelukast between adult and pediatric subjects; 2) the relative contribution of flavin-containing monooxygenase and cytochrome P450 (P450) to the sulfoxidation; and 3) the P450 isoforms responsible for montelukast oxidation. No statistically significant difference was observed in the in vitro kinetics for acyl glucuronidation and oxidative metabolism between the two age groups. Results from studies on heat inactivation of flavin-containing monooxygenase and immunochemical inhibition by an anti-rat NADPH P450 reductase antibody on montelukast oxidation indicated that all oxidative metabolism of montelukast-including diastereomeric sulfoxidations, as well as 21- and methyl-hydroxylations-are catalyzed exclusively by P450. Five in vitro approaches have been used to identify the P450 isoforms responsible for the human liver microsomal oxidation of montelukast. The experimental results consistently indicated that CYP3A4 catalyzes sulfoxidation and 21-hydroxylation, whereas CYP2C9 selectively mediates methyl-hydroxylation.

Acetates↗

PubMed1997

Metabolic profiles of montelukast sodium (Singulair), a potent cysteinyl leukotriene1 receptor antagonist, in human plasma and bile.

Montelukast sodium [1-([(1(R)-(3-(2-(7-chloro-2-quinolinyl)-(E)- ethenyl)phenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio]methyl)cyclopropylacetic acid sodium salt] (MK-476, Singulair) is a potent and selective antagonist of the cysteinyl leukotriene (Cys-LT1) receptor and is under investigation for the treatment of bronchial asthma. To assess the metabolism and excretion of montelukast, six healthy subjects received single oral doses of 102 mg of [14C]montelukast, and the urine and feces were collected. Most of the radioactivity was recovered in feces, with </=0.2% appearing in urine. Based on these results and the reported modestly high oral bioavailability of montelukast, it could be concluded that a major part of the radioactivity was excreted via bile. A second clinical study was conducted to identify biliary metabolites of montelukast. The bile was aspirated using a modified procedure involving a nasogastric tube placed fluoroscopically near the ampulla of Vater, after an oral dose of 54.8 mg of [14C]montelukast. This technique appears to be a new application for drug metabolism studies. The study was conducted with fasted and nonfasted subjects, with the bile being aspirated continuously under suction over periods of 2-8 hr and 8-12 hr after the dose, respectively. Two hours before the end of the collection procedure, cholecystokinin carboxyl-terminal octapeptide was administered iv to stimulate gallbladder contraction. Plasma samples also were collected periodically over 10 hr. Due to the nature of the collection procedure and the limited sampling time, recovery of radioactivity in bile was incomplete and varied from 3 to 20% of the dose. Radiochromatographic and LC-MS/MS analyses of bile showed the presence of one major and several minor metabolites, along with small amounts of unchanged parent drug. The minor metabolites were identified, by LC-MS/MS comparison with synthetic standards or by NMR, as acyl glucuronide (M1), sulfoxide (M2), 25-hydroxy (a phenol, M3), 21-hydroxy (diastereomers of a benzylic alcohol, M5a and M5b), and 36-hydroxy (diastereomers of a methyl alcohol, M6a and M6b) analogs of montelukast. The major metabolite was characterized as a dicarboxylic acid (M4), a product of further oxidation of the hydroxymethyl metabolite M6. Chiral LC-MS/MS analyses of M4 revealed that this diacid, like M5 and M6, was formed in both diastereomeric forms. The levels of metabolites in the systemic circulation were low in the fed as well as fasted subjects, with <2% of the circulating radioactivity being due to metabolites M5a, M5b, M6a, and M6b. Overall, this bile aspiration technique, which is less invasive than either T-tube drainage or fine-needle percutaneous puncture, provided a convenient and expedient means of identifying the biliary metabolites of montelukast, relatively free of contributions from colonic microflora.

Acetates↗

PubMed1997

Control of lymphoproliferative and autoimmune disease in MRL-lpr/lpr mice by brequinar sodium: mechanisms of action.

Brequinar sodium (BQR) was originally developed as an antitumor drug and subsequently as an immunosuppressant for controlling transplant rejection. It has been widely accepted that the antitumor and immunosuppressive activities of BQR are dependent on its ability to inhibit the enzymatic activity of dihydroorotate dehydrogenase, the fourth enzyme in the de novo pyrimidine synthesis pathway. Recently, we discovered that BQR has the ability to inhibit protein tyrosine phosphorylation in anti-CD3-stimulated murine T lymphocytes and to inhibit the activity of src-related protein tyrosine kinases, p56lck and p59fyn. We examined the in vivo activities of BQR in MRL-lpr/lpr mice. We report that the dose of BQR (10 mg/kg/day) that induced anemia, controlled lymphadenopathy and inhibited autoantibody production, also selectively reduced the pyrimidine nucleotide levels in the bone marrow and in the lymph nodes. Coadministration of uridine (1000 mg/kg/day) with BQR completely normalized pyrimidine nucleotide levels in the bone marrow and lymph nodes, and prevented BQR-induced anemia. However, coadministration of uridine with BQR only partially reversed the anti-proliferative effects of BQR, and did not antagonize the inhibitory effect of BQR on autoantibody production. Finally, we report that BQR markedly reduced protein tyrosine phosphorylation in lymph nodes of MRL-lpr/lpr mice. These results collectively suggest that the control of lymphadenopathy and autoantibody production in MRL-lpr/lpr mice by BQR is only partially dependent on inhibition of pyrimidine nucleotide synthesis, and suggest a critical role for in vivo inhibition of protein tyrosine phosphorylation.

Animals↗

PubMed1997

Coronary revascularization in women.

Women who undergo revascularization with CABG or PTCA may experience more negative acute outcomes compared with men. These gender differences in acute outcome are partly explained by the size of coronary arteries, baseline differences in clinical risk factors, and the unfavorable cardiovascular profiles seen in women. However, once women have survived the revascularization procedure, long-term outcomes are generally similar to those of men. Risk factor identification and modification is an important approach to enhance our ability to reduce long-term restenosis and progression of atherosclerosis following revascularization in women as well as men. After these interventions, only one in three patients benefits from comprehensive risk factor intervention. Nurses are in key positions to approach patients and their families at the time of these major interventions when they are likely to be more receptive to the idea of risk factor modification.

Angioplasty, Balloon, Coronary↗

PubMed1997

[Preclinical studies on thymidine kinase gene (TK) and gancyclovir system for treatment of malignant astrocytoma].

OBJECTIVE: To study preclinically TK gene mediated GCV system for treatment of human malignant astrocytoma. METHODS: The TK gene (TKc) was isolated from a Chinese strain of HSV-1 (17) and sequenced. A retroviral vector with TKc (pLTKcSN) and its package cell line (pLTKcSN/VPC) were constructed. The in vitro assay for its activity was performed by mixed cultures of TK producer cells and rat glioma C6 cells after treatment with GCV. The in vivo efficacy was examined by in situ inoculation of virus-producer cells after intracerebral implantation of C6 cells. Safety tests were analyzed by inoculation of pLTKcSN/VPC and injection of GCV, in mouse, rat, and Rhesus monkey, evaluated by histopathological examination and in situ hybridization with TK probe. RESULTS: TKc gene contained 5 nucleotide difference covering 2 amino acid variation. The retroviral vector pLTKcSN and its producer cell pLTKcSN/VPC (with a titer at 0.5-1.0 x 10(6) CFU/ml) can efficiently mediate cytotoxicity of GCV to C6 cells, both in vitro and in vivo. The above system had no serious adverse effect and remarkable or irreversible pathological changes in 48 mice, 24 rats and 6 Rhesus monkeys. CONCLUSION: The preclinical studies indicated that it would be effective and safe for clinical trial after approval.

Amino Acid Sequence↗

PubMed1997

[Usage of double immuno-enzyme labeled staining method in forensic pathology].

In this paper we report a kind of double immunoenzyme labelled staining method (single enzyme method). The principle of the method is that HPR will show blue-black color when it meet DAB-CoCL2/H2O2, while it will show brown color as it meet DAB/H2O2, two colors constract very remarkably. This method was used to detect the antigens of hearts and brains which obtained from forensic autopsy. The results showed that the method was sensitive, simple and economical. One of the advantages is that the stained sections can keep for a long time. Thus, is very practical for forensic pathology.

Brain↗

PubMed1997

[Isolation and identification of DNA fragments frequently deleted from tumor cell lines of human esophageal cancer].

OBJECTIVE: To clone tumor suppressor genes associated with human esophageal cancer (EC). METHODS: DNA fragments deleted from cell lines of esophageal cancer EC8712 and EC8733 were isolated by using modified genomic substractive hybridization. Twenty EC tissues paired with adjacent normal mucosa were analysed by Southern blot and PCR with these fragments as probes. RESULTS: Seven DNA fragments deleted from EC cell lines obtained were named as 12H1, 12H2, 33H3, 33H4, 12B1, 33B2 and 33B3. Sequencing revealed their size of 512bp, 428bp, 509bp, 355bp, 680bp (partially sequencing), 519bp and 425bp, respectively. 12H1 and 33H3 showed high homology (98%) to a new repeated sequence in human genome. 33H4 displayed 87% nucleotide identity with human alphoid-like repetitive sequence located on chromosome 17. 12B1 was homologous (90%) to LINE 1 transoposon containing two open reading frames. 12H2, 33B2 and 33B3 were novel sequences. These DNA fragments were deleted in 20%-60% of EC tissues and in 10%-20% of adjacent mucosa. CONCLUSIONS: Loss of 33H4 may be accompanied by deletion of an adjacent gene. 12B1 as transposon may suppress the tumorigenesis by activating suppressor genes or/and by inactivating oncogenes. 12H1/33H3, 12H2, 33B2 and 33B3 may be candidates of tumor suppressor genes associated with the development and the progression of esophageal cancer.

Cloning, Molecular↗

PubMed1997

[Dynamic observations on pulmonary function in retired miners exposed to nickel dust].

Pulmonary ventilation functions were determined dynamically in 34 retired miners exposed to nickel dust and 28 non-exposed ones in 1981, 1988 and 1995, respectively to study their damage and change patterns. Results showed that mean forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were lower in retired miners than those in controls at any time of determination. FVC and FEV1 lowered with time both in retired or control groups, with statistical significance. However, decrease of FVC and FEV1 in the retired was more than that in the controls whether during 1981 to 1988, or 1988 to 1995, or 1981 to and 1995. And, proportion of abnormal FVC and FEV1 increased more and extent of their abnormality was more severe in retired group than those in controls.

Dust↗

PubMed1997

[Influence of low energy He-Ne laser on spinal motor nerve cell].

The object of this experimental study was to investigate the influence of low-energy He-Ne laser on the motor nerve cells of the spinal cord. The experimental study included as follws: (1) Four rabbits were used in this experiment. The L5-6 spinal cord segment was irradiated by He-Ne laser percutaneously, the nerve velocity of the comon peroneal nerve was measured in order to determine the function of the spinal motor nerve cells when the peripheral nerve was intact. (2) The common peroneal nerve was transected on one side wothout repair, two weeks after laser irradiation, the grey mater of the spinal cord of L5-6 segment was procured for electronic microscopic examination. (3) The common peroneal nerve on the contralateral side was transected and followed by end-to-end anastomosis, and laser irradiation was done on the same spinal cord segment. Two weeks after irradiation, the nerve velocity of the common peroneal nerve and the toe expanding test were investigated. The results were: (1) the He-Ne laser can influence the spinal motor nerve cells function as expressed by latent rate when the peripherial nerve is intact. i.e. the nerve velocity is slower than mormal, and the amplitude is markedly decreared. (2) the change of the microstructure of the spinal motor nerve cells is comparatively slight in the 10 and 15 minutes groups. (3) the recovery of the nerve velocity and the toe expansion are more earlier in the 15 min. group. In short, the low-energy He-Ne laser can influence the function of the spinal motor nerve cells.

Animals↗

PubMed1997

[Influence of low energy He-Ne laser on regeneration of peripheral nerve].

The purpose of this experiment was to elucidate the influence of the low-energy He-Ne laser on the function of regeneration of peripheral nerve. Forty-four rabbits about 2.5 kg body weight were used in the experiment. The animals were divided into 4, 8, 12, 16 weeks groups according to the observation period. Six animals were used in each irradiated group and in the control group 5 rabbits were used in each observation period. Regeneration of the axon and myelinc sheath, the latent rate of the common peroneal nerve, the conditions of the anterior tibital muscle and the toe expansion test were all observed systematically in both groups. The experimental results was: A few thin regenerated axon was seen at 4 weeks in the irradiated group, while in the control group it might be seen at 8 weeks, the P value was < 0.01. A low amplitude latent rate of the common peroneal nerve is determined at the peroneal side of the anterior tibial muscle in a few animal at 4 weeks of the irradiated group, and it is not observed in the control group, from 12 to 16 weeks. THe latent rate of the common peroneal nerve was the irradiated group than in the controlled, the P value was < 0.01. The regeneration of the myeline sheath was evident in the irradiated group, and also the slstion of the musdle fibers anterior tibial muscle was clearly visible than the controlled. 16 weeks postoperatively, the toe expansion test was normal in the irradiated group, while in the control group it was the same as seen at 12 weeks after operation in the irradiated group. Now it was certain that the low-energy He-Ne laser could promole the function of the spinal motor nerve cells and accelerate the axonal regeneration.

Animals↗

PubMed1997

[An experimental study of bioactive glass ceramics as orbital implants].

One eyeball of experimental rabbits was enucleated in routine procedure, and then implanted the biocative glass ceramic (BGC). No rejection was observed during the postoperation period. After three months of implantation, they were examined with ultrasound, and a venous-flow-like spectra was detected in the ceramic implant. After six months of implantation, the implans were examined histologically; the ingrowth fibrovascular tissue filled the 90% gaps of the implant. The results suggest that the bioactive glass ceramic implants made in China possess acceptable histocompatibility.

Animals↗

PubMed1996

Kinetic analysis of the catalytic domain of human cdc25B.

The Cdc25 cell cycle regulator is a member of the dual-specificity class of protein-tyrosine phosphatases that hydrolyze phosphotyrosine- and phosphothreonine-containing substrates. To study the mechanism of Cdc25B, we have overexpressed and purified the catalytic domain of human Cdc25B (Xu, X., and Burke, S. P. (1996) J. Biol. Chem. 271, 5118-5124). In the present work, we have analyzed the kinetic properties of the Cdc25B catalytic domain using the artificial substrate 3-O-methylfluorescein phosphate (OMFP). Steady-state kinetic analysis indicated that the kcat/Km for OMFP hydrolysis is almost 3 orders of magnitude greater than that for p-nitrophenyl phosphate hydrolysis. Like other dual-specificity phosphatases, Cdc25 exhibits a two-step catalytic mechanism, characterized by formation and breakdown of a phosphoenzyme intermediate. Pre-steady-state kinetic analysis of OMFP hydrolysis indicated that formation of the phosphoenzyme intermediate is approximately 20 times faster than subsequent phosphoenzyme breakdown. The resulting burst pattern of product formation allowed us to derive rate constants for enzyme phosphorylation (26 s-1) and dephosphorylation (1.5 s-1) as well as the dissociation constant for OMFP (0.3 mM). Calculations suggest that OMFP binds with higher affinity and reacts faster with Cdc25B than does p-nitrophenyl phosphate. OMFP is a highly efficient substrate for the dual-specificity protein-tyrosine phosphatases VHR and rVH6, but not for two protein-tyrosine phosphatases, PTP1 and YOP. The ability to observe distinct phases of the reaction mechanism during OMFP hydrolysis will facilitate future analysis of critical catalytic residues in Cdc25 and other dual-specificity phosphatases.

Amino Acid Sequence↗