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Biomedical subjects

J Wei

Publications and source records attributed to J Wei.

At least 73 records · Page 4Linked to original sources
PubMed2001

[Adsorption of TNF alpha onto the amino acid-modified NK-110 resin].

It is a effective way to remove Tumor Necrosis Factor(TNF alpha) from plasma by adsorbent. In the present study, NK-110 was modified by 8 amino acids to prepare the adsorbents to be used in the static adsorption experiments of TNF alpha. We have studied the adsorption capacity, kinetic profiles and adsorption isoterm of Cys modified NK-110, and some comparison were made between Cys modified NK-110 and unmodified one. The experimental results show that the Cys modified NK-110 exhibited superior adsorption capacity which is 7683.80 u/mL, and the adsorption percentage is 85.38% at 120 min in stable adsorption. Compared with unmodified NK-110, the Cys-modified one with high adsorption velocity. Furthermore, adsorption isotherms were also studied on Cys-modified and bare NK-110, bot showed to be of "L" shape at 37 degrees C. The adsorption amount increased as the concentration of TNF alpha increased, however, the adsorption percentage is stable adsorbed by Cys-modified NK-110, whereas it is decreased by bare one. The results demonstrating that Cys can significantly raised the adsorption capacity.

Adsorption↗
PubMed2001

High levels of HER-2 expression alter the ability of epidermal growth factor receptor (EGFR) family tyrosine kinase inhibitors to inhibit EGFR phosphorylation in vivo.

The epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases have been implicated in the development, progression, and severity of several human cancers and are attractive targets for therapeutic intervention. SU11925 was developed as a small molecule inhibitor of the tyrosine kinase activity of both EGFR and HER-2. In cellular assays, SU11925 exhibited similar potency against EGFR and HER-2, inhibiting EGF-stimulated EGFR autophosphorylation in A431 (human epidermoid carcinoma) cells with an IC(50) of 30 nM and HER-2 phosphorylation in SK-OV-3TP5 (human ovarian carcinoma) cells with an IC(50) of 38 nM. In contrast to its similar activity against the two targets in cellular assays, approximately 10-fold higher plasma concentrations of SU11925 were required to inhibit HER-2 phosphorylation in HER-2-overexpressing tumors compared with EGFR phosphorylation in EGFR-overexpressing tumors in vivo. Consistent with the proposed mechanism of action of this inhibitor, SU11925 inhibited the s.c. growth of EGFR- and HER-2-dependent tumors in athymic mice at doses that produced substantial inhibition of target receptor phosphorylation in vivo. An unexpected finding from these studies was that higher plasma concentrations of SU11925 were required to inhibit EGFR phosphorylation in vivo in tumors that also express high levels of HER-2 than in tumors that express EGFR alone. This observation, which suggests that it is more difficult to inhibit EGFR phosphorylation in vivo in cells that express high levels of HER-2, was confirmed with ZD1839 (Iressa), a selective EGFR inhibitor that also targets the tyrosine kinase catalytic site. The potential clinical implications of this observation are discussed.

Animals↗
PubMed2001

Regulation of osteopontin expression in a rat model of urolithiasis.

OBJECTIVE: To investigate the relationship between the expression and regulation of osteopontin (OPN) and urolithiasis. METHODS: Normal and stone model rats were treated with 1,25-dihydroxyvitamin D3(D3), vitamin K, testosterone or estradiol for 7 days, and the expression of osteopontin and its mRNA were detected with immunohistochemistry and Northern blot, respectively. Crystals deposited in rat kidneys were observed with a polarization microscope. The concentrations of crystal components in rat urine were determined. RESULTS: The results showed that vitamin K, testosterone and estradiol up-regulated the expression of OPN mRNA and its protein, thus decreasing the precipitation of calcium oxalate in rat kidneys. D3 increased the concentration of calcium in urine, and accelerated the sedimentation of calcium oxalate in rat kidneys. CONCLUSIONS: These findings indicate that OPN may be an important macromolecule in the normal endogenous inhibition of the formation of urolithiasis. Vitamin K, testosterone and estradiol inhibit the formation of stones via up-regulating the expression of OPN in kidneys, while D3 over dose may accelerate the process.

Animals↗
PubMed2001

Replacement of the p16 gene in human ovarian cancer cells.

OBJECTIVE: To study the inhibitory effects of retrovirus-mediated p16 gene on the human ovarian cancer cell line CAOV3. METHODS: The recombinant eukaryotic expression vector pDOR-p16 containing exogenous human wt-p16 cDNA and vector with neomycin resistance gene only were introduced into a CAOV3 cell line which does not express p16 endogenously by lipofectamine-mediated gene transfection. By using polymerase chain reaction amplification, mRNA in situ hybridization and immunocytochemistry, the clones obtained were tested for their efficiency of transfection and effects of vector expression. Their biologic behavior was observed further. RESULTS: Exogenous wt-p16 was transferred into CAOV3 cells successfully and permanent expression was obtained. The growth rate of the transfected CAOV3 cells in regular medium and soft agar was inhibited, and the tumorigenicity in nude mice showed that two of four mice failed to form tumors, and the others developed tumors 7 to 14 days later than mice of the contrast group. The percentage of phase G1 cells increased and that of phase S cells decreased. Under electron microscope, the ultrastructural changes of the cells revealed necrosis and growth retardation. CONCLUSIONS: The p16 gene plays an important role in the generation and development of ovarian carcinoma. This study might provide experimental evidence for gene therapy in human ovarian cancer.

Animals↗
PubMed2001

[Study on variation and interrelations of characteristics at ginseng germplasms].

The variation and interrelations of some characteristics of Panax ginseng germplasms(lines), which were five selfmating generations of some single plants were studied. Methods of multivariate analysis, such as correlation, regression, or clustering, and coefficient of variation were used. The results were of benefit to the breeding and standardized planting of Panax ginseng.

Genetic Variation↗
PubMed2001

[Cloning and expression of two garlic virus coat protein genes].

The coat protein(CP) genes of garlic mosaic virus(GMVc) and garlic latent virus(GLVc) isolated from garlic(Allium) plants in Tianjin, China, were amplified from an established cDNA library by PCR method and subsequently expressed in E. coli. using the pET-30a expression system. The determined sequences of GMVc and GLVc CP genes show that the complete GMVc CP gene has 867 nucleotides encoding 289 amino acids. It has 88.5% and 97.2% homology, at the levels of nucleotide and amino acid, respectively, to a reported GMV, indicating that it belongs to Potyvirus. The complete GLVc CP gene has 885 nucleotides coding for 294 amino acids. It has 73.6% and 90.9% homologous percents, in nucleotide and amino acid, respectively, compared to a previously reported GLV, suggesting that it is a member of Carlavirus. The expressed products presented in inclusion body and were analyzed by SDS-PAGE. The molecular weights of GMVc and GLVc CPs appear in 32 kD and 34 kD size, respectively, which are consistent with the deduced sizes of these two CPs. These data will be virtually significant to the further investigation of viruses infecting parlic plant, the control of garlic virus diseases and the production of virus-freed garlic plants.

Capsid Proteins↗
PubMed2001

[Pharyngeal passage tube treatment for obstructive apnea syndrome].

OBJECTIVE: To investigate the therapeutical effect of pharyngeal passage tube for OSAS. METHODS: Fifty-seven patients were treated during May 1995 to August 1999. All patients were examined by GKD-405 A polysomnography for apnea index (AI), hypnea index (HI), AHI (AI + HI) at cetera 7 items index before and after pharyngeal passage tube treatment. RESULTS: After treatment, the longest time of apnea shortened from (54.82 +/- 20.83) s to (25.74 +/- 9.50) s, the AHI lessened from 70.82 +/- 18.06 to 30.00 +/- 10.10, the oxygen desaturation increased from (62.36 +/- 11.53)% to (78.68 +/- 12.09)%. After treatment, the recorded parameters showed obvious therapeutical effect (P < 0.05-0.001, t values is from 2.20 to 15.29, the snore loudness of all patients dropped from (84.32 +/- 18.51) dB to (32.64 +/- 10.16) dB. The therapeutical successful rate was 87.72%. The long-term use rate (over 6 months) was 72.73%. CONCLUSION: The pharyngeal passage tube has obvious effect for patients suffering from severe OSAS. It is recommended for the treatment of OSAS as a conservative method.

Adult↗
PubMed2000

Benign prostatic glands at surgical margins of radical prostatectomy specimens: frequency and associated risk factors.

OBJECTIVES: Elevation of serum prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer is considered a surrogate marker of therapeutic failure. The most likely explanation for early PSA failure is considered to be due to local recurrent disease, provided the patient had a nondetectable PSA level after radical prostatectomy. Others have recently suggested that benign prostatic glands located on the surgical margins may often lead to detectable PSA levels. We examined the frequency of benign prostatic glands at the surgical margins of radical prostatectomy specimens and the factors associated with this finding. METHODS: One hundred nineteen consecutive radical prostatectomies were performed by two experienced oncologic surgeons. Whole-mount sectioning of the prostatectomy specimens was performed at 3-mm intervals. Bivariate and multivariate analyses were used to determine which clinical and pathologic factors were associated with benign glands on inked surgical margins. RESULTS: Of the 119 cases, 13 (11%) had benign glands on the inked surgical margins. Four of these 13 had tumor on the inked margins. The remaining 9 cases (8%) were organ confined (pT2), with negative surgical margins. Benign glands were most often seen to involve the apex focally (7 of 9 cases). On bivariate and multivariate analyses, a high Gleason score and prostate gland volume were significantly associated with finding benign glands on the surgical margins. Only 2 of 86 patients with follow-up had PSA recurrence at 59 and 67 days and neither had benign glands on the inked surgical margins. CONCLUSIONS: The presence of benign prostatic glands identified on inked surgical margins was an infrequent occurrence in this consecutive series of 119 whole-mount prostatectomy specimens. When benign glands were identified, they most often consisted of 1 to 3 glands at the apex margin. These findings suggest that benign glands on surgical margins are an unusual cause of postoperative detectable PSA.

Follow-Up Studies↗
PubMed2000

Characterization of salt-induced changes in gene expression in tomato (Lycopersicon esculentum) roots and the role played by abscisic acid.

Examination of tomato (Lycopersicon esculentum Mill) root mRNA profiles by differential display-polymerase chain reaction (DD-PCR) revealed that a salt treatment induced, promoted or repressed the expression of a number of genes. The majority of the observed changes were indicative of a rapid and transient salt-induced alteration in gene expression. Twenty partial cDNAs corresponding primarily to salt-induced or up-regulated mRNAs were subsequently cloned and sequenced. The role of abscisic acid (ABA) in regulating salt-responsive gene expression in roots was explored. The DD-PCR data indicate that the majority of the salt-induced changes in the root mRNA profile occurred in an ABA-independent manner. The expression of genes corresponding to six cDNAs was shown unequivocally to be responsive to a salt treatment by RNA blot hybridization. Just two of these were responsive to exogenous ABA and, in salt-treated roots of the ABA-deficient mutant flacca, all were expressed to a level comparable to that in the wild-type. The identity of two of the salt-responsive partial cDNAs is known. The deduced amino acid sequence of one was similar to that of laccases that polymerize a variety of substrates to form resilient structures within the cell wall. One other shared amino acid sequence similarity with the C-terminus of a tobacco pathogen-induced oxygenase (PIOX). It is possible that the PIOX is involved in generating signaling molecules that mediate a general stress response.

Journal Article↗
PubMed2000

A common polymorphism associated with antibiotic-induced cardiac arrhythmia.

Drug-induced long QT syndrome (LQTS) is a prevalent disorder of uncertain etiology that predisposes to sudden death. KCNE2 encodes MinK-related peptide 1 (MiRP1), a subunit of the cardiac potassium channel I(Kr) that has been associated previously with inherited LQTS. Here, we examine KCNE2 in 98 patients with drug-induced LQTS, identifying three individuals with sporadic mutations and a patient with sulfamethoxazole-associated LQTS who carried a single-nucleotide polymorphism (SNP) found in approximately 1.6% of the general population. While mutant channels showed diminished potassium flux at baseline and wild-type drug sensitivity, channels with the SNP were normal at baseline but inhibited by sulfamethoxazole at therapeutic levels that did not affect wild-type channels. We conclude that allelic variants of MiRP1 contribute to a significant fraction of cases of drug-induced LQTS through multiple mechanisms and that common sequence variations that increase the risk of life-threatening drug reactions can be clinically silent before drug exposure.

Amino Acid Sequence↗
PubMed2000

Salicylamide inhibitors of influenza virus fusion.

Structural variation of the quinolizidine heterocycle of the influenza fusion inhibitor BMY-27709 was examined by several topological dissections in order to illuminate the critical features of the ring system. This exercise resulted in the identification of a series of synthetically more accessible decahydroquinolines that retained the structural elements of BMY-27709 important for antiviral activity. The 2-methyl-cis-decahydroquinoline 6f was the most potent influenza inhibitor identified that demonstrated an EC50 of 90 ng/mL in a plaque reduction assay.

Animals↗
PubMed2000

Identification and characterization of the iron regulatory element in the ferritin gene of a plant (soybean).

Iron increases ferritin synthesis, targeting plant DNA and animal mRNA. The ferritin promoter in plants has not been identified, in contrast to the ferritin promoter and mRNA iron-responsive element (IRE) in animals. The soybean leaf, a natural tissue for ferritin expression, and DNA, with promoter deletions and luciferase or glucuronidase reporters, delivered with particle bombardment, were used to show that an 86-base pair fragment (iron regulatory element (FRE)) controlled iron-mediated derepression of the ferritin gene. Mutagenesis with linkers of random sequence detected two subdomains separated by 21 base pairs. FRE has no detectable homology to the animal IRE or to known promoters in DNA and bound a trans-acting factor in leaf cell extracts. FRE/factor binding was abrogated by increased tissue iron, in analogy to mRNA (IRE)/iron regulatory protein in animals. Maximum ferritin derepression was obtained with 50 microm iron citrate (1:10) or 500 microm iron citrate (1:1) but Fe-EDTA was ineffective, although the leaf iron concentration was increased; manganese, zinc, and copper had no effect. The basis for different responses in ferritin expression to different iron complexes, as well as the significance of using DNA but not mRNA as an iron regulatory target in plants, remain unknown.

Base Sequence↗
PubMed2000

Monitoring enzyme catalysis with mass spectrometry.

Mass spectrometry is a rapid, sensitive, and accurate quantitative approach for the direct monitoring of enzyme-catalyzed reactions that does not require a chromophore or radiolabeling and thus provides a viable alternative to existing analytical techniques. In this study the proteolysis of intact viral capsid proteins, the alpha-glucosidase-catalyzed hydrolysis of p-nitrophenyl-alpha-glucopyranoside and the lipoprotein lipase-catalyzed ester hydrolysis of resorufin were examined. Matrix-assisted laser desorption/ionization and electrospray ionization mass spectrometry were used to examine the proteolysis of viral protein capsids, providing information about capsid dynamics and the stabilizing force of viral protein/RNA interactions. In addition, k(cat) and K(m) values of enzyme-catalyzed hydrolysis were obtained (without the use of a chromophore). These results also demonstrate the effect an unnatural substrate can have on enzyme activity. Overall, mass spectrometry provides for efficient and quantitative analysis of enzyme-catalyzed reactions, as well as the direct observation of reaction dynamics.

Animals↗
PubMed2000

The role of enzyme isomerization in the native catalytic cycle of the ATP sulfurylase-GTPase system.

ATP sulfurylase, from E. coli Kappa-12, is a GTPase.target complex that conformationally couples the free energies of GTP hydrolysis and activated sulfate (adenosine 5'-phosphosulfate, or APS) synthesis. Energy coupling is achieved by an allosterically driven isomerization that switches on and off chemistry at specific points in the catalytic cycle. This coupling mechanism is derived from the results of model studies using analogue complexes that mimic different stages of the native catalytic cycle. The current investigation extends the analogue studies to the native catalytic cycle. Isomerization is monitored using the fluorescent, guanine nucleotide analogues mGMPPNP (3'-O-(N-methylanthraniloyl)-2'-deoxyguanosine 5'-[beta, gamma-imido]triphosphate) and mGTP [3'-O-(N-methylanthraniloyl)-2'-deoxyguanosine 5'-triphosphate]. The isomerization is shown to be initiated by an allosteric interaction that requires the simultaneous occupancy of all three substrate-binding sites. Stopped-flow fluorescence and single-turnover studies were used to define and quantitate the isomerization mechanism, and to show that the isomerization precedes and rate-limits both GTP hydrolysis and APS synthesis. These findings are incorporated into a model of the energy-coupling mechanism.

Adenosine Phosphosulfate↗
PubMed2000

Determination of biological toxins using capillary electrokinetic chromatography with multiphoton-excited fluorescence.

We report a highly sensitive and rapid strategy for characterizing biological toxins based on capillary electrokinetic chromatography with multiphoton-excited fluorescence. In this approach, aflatoxins B1, B2, and G1 and the cholera toxin A-subunit are fractionated in approximately 80 s in a narrow-bore electrophoretic channel using the negatively charged pseudostationary phase, carboxymethyl-beta-cyclodextrin. The aflatoxins--highly mutagenic multiple-ringed heterocycles produced by Aspergillus fungi--are excited at the capillary outlet through the simultaneous absorption of two to three 750-nm photons to yield characteristic blue fluorescence; cholera toxin A-subunit, the catalytic domain of the bacterial protein toxin from Vibrio cholera, is excited through an unidentified multiphoton pathway that apparently includes photochemical transformation of an aromatic residue in the polypeptide. The anionic carboxymethyl-beta-cyclodextrin, used to chromatographically resolve the uncharged aflatoxins, enhances emission from these compounds without contributing substantially to the background. Detection limits for these toxins separated in 2.1-micron-i.d. capillaries range from 4.4 zmol (approximately 2700 molecules) for aflatoxin B2 to 3.4 amol for the cholera toxin A-subunit. Larger (16-micron-i.d.) separation capillaries provide concentration detection limits for aflatoxins in the 0.2-0.4 nM range, severalfold lower than achieved in 2.1-micron capillaries. These results represent an improvement of > 10(4) in mass detectability compared to previously published capillary separations of aflatoxins and demonstrate new possibilities for the analysis of proteins and peptides.

Bacterial Toxins↗
PubMed2000

Searching for a locus for schizophrenia within chromosome Xp11.

Three gene-rich loci-HS212G6, HSU93305, and HS884M20-within the short arm of the X chromosome have been examined for allelic association with schizophrenia by the transmission disequilibrium test in 70 families of male individuals affected with schizophrenia. Neither the HS212G6 nor HS884M20 was found to be associated with schizophrenia. The HSU93305 locus, however, was significantly associated with schizophrenia (X(2)=17.92, df=3, P<0.001). The HSU93305 locus contains four distinct genes. They code, respectively, for A4 differentiation-dependent protein, triple LIM domain protein, synaptophysin, and calcium channel alpha-1 subunit. It is possible that one of these genes or some loci near to it may predispose a vulnerability to schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:4-7, 2000.

Base Sequence↗
PubMed2000

Novel KCNQ1 mutations associated with recessive and dominant congenital long QT syndromes: evidence for variable hearing phenotype associated with R518X.

Congenital long QT syndrome may be transmitted as either an autosomal dominant or recessive trait. Two families with the autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS), and one family with the autosomal dominant Romano-Ward syndrome (RWS) were evaluated for mutations in KCNQ1. Two different novel frameshift mutations were discovered in one of the JLNS families (1188delC) and in the RWS family (504delG). A third allele (R518X) was observed in the second JLNS family. The R518X allele was previously associated with recessive long QT syndrome without deafness, but was present in a congenitally deaf proband in our study. These data extend the range of known KCNQ1 mutations associated with both recessive and dominant forms of congenital long QT syndrome, and demonstrate that the R518X allele may be associated with or without congenital deafness.

Adolescent↗