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Biomedical subjects

J Wei

Publications and source records attributed to J Wei.

At least 55 records · Page 3Linked to original sources

Complete genome sequence and comparative genomics of Shigella flexneri serotype 2a strain 2457T.

We determined the complete genome sequence of Shigella flexneri serotype 2a strain 2457T (4,599,354 bp). Shigella species cause >1 million deaths per year from dysentery and diarrhea and have a lifestyle that is markedly different from those of closely related bacteria, including Escherichia coli. The genome exhibits the backbone and island mosaic structure of E. coli pathogens, albeit with much less horizontally transferred DNA and lacking 357 genes present in E. coli. The strain is distinctive in its large complement of insertion sequences, with several genomic rearrangements mediated by insertion sequences, 12 cryptic prophages, 372 pseudogenes, and 195 S. flexneri-specific genes. The 2457T genome was also compared with that of a recently sequenced S. flexneri 2a strain, 301. Our data are consistent with Shigella being phylogenetically indistinguishable from E. coli. The S. flexneri-specific regions contain many genes that could encode proteins with roles in virulence. Analysis of these will reveal the genetic basis for aspects of this pathogenic organism's distinctive lifestyle that have yet to be explained.

Base Sequence↗

Nitric oxide inhibits expression of cytochrome B in endotoxin-stimulated murine macrophages.

In LPS-mediated states of sepsis, inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production inhibit cellular respiration and mitochondrial electron transport. NO has been demonstrated to inhibit mitochondrial respiration by nitrosylation of the iron-sulfur centers of aconitase, complex I (NADH-ubiquinone oxidoreductase), complex II (succinate-ubiquinone oxidoreductase), and complex IV (cytochrome c oxidase). However, little is known of the effect of NO on expression of critical proteins in the electron transport chain. In ANA-1 murine macrophages, LPS-mediated NO synthesis decreases Cyt b protein expression and steady-state mRNA levels. Mitochondrial run-on analysis demonstrates unaltered Cyt b mitochondrial gene transcription. In this study utilizing LPS-stimulated ANA-1 murine macrophages, we demonstrate that expression of the mitochondrial protein, Cyt b, is significantly decreased as the result of a unique and previously unknown, NO-dependent posttranscriptional regulatory mechanism. (c)2001 Elsevier Science.

Animals↗

Trends in the utilization of androgen-deprivation therapy for patients with prostate carcinoma suggest an effect on mortality.

BACKGROUND: After a surge in the incidence of prostate carcinoma in the early 1990s, diminishing rates of mortality became apparent in 1993. This decrease in mortality is unlikely to be explained entirely by treatment with curative intent alone following screen-detected cases, because the time frame between detection and mortality remains relatively brief. METHODS: This study used incidence and initial treatment data from the Detroit area SEER registry between 1973 and 1998 in addition to mortality data covering the Metropolitan Detroit area obtained from the Michigan Department of Community Health. Data for Caucasian and African-American men were analyzed. The use of androgen-deprivation therapy, which evolved during the study period, was evaluated in conjunction with mortality and incidence trend data for consideration of etiologic contributions. RESULTS: The incidence of prostate carcinoma, as noted previously in national data, increased sharply in 1988, peaking in 1992 in Southeast Michigan, whereas mortality rates began to decrease in approximately 1993, with a sustained decrease to the latest recorded data in 1998. These trends were identical in Caucasians and African Americans. A sharp increase in the use of androgen-deprivation therapy began in 1990. This use of androgen-deprivation therapy is high and sustained for patients with early-stage disease, increases for several years, and then diminishes for patients with regional disease. The use also diminished through the 1990s for patients with late-stage disease, paralleling the decrease in the incidence rate for late-stage disease. CONCLUSIONS: The pattern of androgen-deprivation therapy usage was consistent with that for hormonal monotherapy and adjuvant and neoadjuvant therapy. These findings suggest that androgen-deprivation therapy may contribute, along with advances in diagnostic techniques and curative therapy with radiation or surgery, toward decreasing prostate carcinoma mortality rates in Southeast Michigan.

Adult↗

An approach to the identification of potent inhibitors of influenza virus fusion using parallel synthesis methodology.

Structure-activity studies associated with the salicylic acid-derived inhibitor of influenza fusion, BMY-27709, were examined using a parallel synthesis approach. This SAR survey led to the discovery of potent influenza inhibitory activity in a series of aromatic amides and thioamides derived from 1,3,3-trimethyl-5-hydroxycyclohexylmethylamine. Select compounds were characterized as inhibitors of the H1 subtype of influenza A viruses that act by preventing the pH-induced fusion process, thereby blocking viral entry into host cells. In a plaque-reduction assay, the most potent inhibitors displayed EC(50) values of 0.02-0.14 microg/mL.

Amines↗

Influence of clay minerals on the hydrolysis of carbamate pesticides.

Using batch experiments, we investigated the influence of clay minerals (montmorillonite, beidellite, illite, and vermiculite) on the hydrolysis of five carbamate pesticides: carbosulfan, carbofuran, aldicarb, pirimicarb, and chlorpropham. Compared to the other minerals, montmorillonite had the strongest influence on the hydrolysis of these carbamates. Montmorillonite enhanced the hydrolysis of carbosulfan and aldicarb. In contrast, the hydrolysis of chlorpropham was inhibited by montmorillonite, probably because of its strong adsorption on montmorillonite. The hydrolysis of pirimicarb was not affected by montmorillonite. The presence of organic substances, phosphate, and fluoride in suspensions decreased the catalytic activity of montmorillonite. Surface acidity of montmorillonite and/or formation of surface chelates are probably the key factors of surface catalysis in the case of the hydrolysis of carbosulfan.

Adsorption↗

Viral capsid mobility: a dynamic conduit for inactivation.

Mass spectrometry and fluorescent probes have provided direct evidence that alkylating agents permeate the protein capsid of naked viruses and chemically inactivate the nucleic acid. N-acetyl-aziridine and a fluorescent alkylating agent, dansyl sulfonate aziridine, inactivated three different viruses, flock house virus, human rhinovirus-14, and foot and mouth disease virus. Mass spectral studies as well as fluorescent probes showed that alkylation of the genome was the mechanism of inactivation. Because particle integrity was not affected by selective alkylation (as shown by electron microscopy and sucrose gradient experiments), it was reasoned that the dynamic nature of the viral capsid acts as a conduit to the interior of the particle. Potential applications include fluorescent labeling for imaging viral genomes in living cells, the sterilization of blood products, vaccine development, and viral inactivation in vivo.

Animals↗

Solution structure determination and mutational analysis of the papillomavirus E6 interacting peptide of E6AP.

E6AP is a cellular protein that binds cancer-related papillomaviral E6 proteins. The E6 binding domain, called E6ap, is located on an 18-amino acid segment of E6AP. The corresponding peptide was synthesized and its structure determined by nuclear magnetic resonance spectroscopy. The overall structure of the peptide is helical. A consensus E6-binding sequence among different E6 interacting proteins contains three conserved hydrophobic residues. In the structure of the E6AP peptide, the three conserved leucines (Leu 9, Leu 12, and Leu 13) form a hydrophobic patch on one face of the alpha-helix. Substitution of any of these leucines with alanine abolished binding to E6 protein, indicating that the entire hydrophobic patch is necessary. Mutation of a glutamate to proline, but not alanine, also disrupted the interaction between E6 and E6AP protein, suggesting that the E6-binding motif of the E6AP protein must be helical when bound to E6. Comparison of the E6ap structure and mutational results with those of another E6-binding protein (E6BP/ERC-55) indicates the existence of a general E6-binding motif.

Amino Acid Sequence↗

Electrospray ionization mass spectrometry of tribenzyltin substituted-phenoxyacetate compounds.

Hydrolysis products of organotin compounds RC(6)H(4)OCH(2)COOSn(CH(2)ph)(3) (R = o-NO(2), 1; m-NO(2), 2; p-NO(2), 3; o-CH(3), 4; o-OCH(3), 5; o-Cl, 6; o-Br, 7) and RC(6)H(3)OCH(2)COOSn(CH(2)ph)(3) (R = o,o-2CH(3), 8, o-OCH(3), p-CHO, 9; o,p-2Cl, 10), produced in aqueous acetonitrile solution, have been investigated by electrospray mass spectrometry (MS) and MS(n) techniques. The complexes [Y(2)SnXR'](-), [Y(3)SnXR'](-), [Y(3)SnX(2)R'](-), [Y(2)SnX(3)R'](-), and fragment ions of [Y(3)SnR'](-), plus abundant RC(6)H(4)(or RC(6)H(3))OCH(2)COO(-) and RC(6)H(4)(or RC(6)H(3))O(-) ions are observed in negative mode, whereas the protonated molecular ion [M + H](+), complexes [Y(2)SnXR'](+), [Y(3)SnXR'](+), [Y(2)SnX(2)R'](+), [Y(3)SnX(2)R'](+), [Y(2)SnX(3)R'](+), [Y(3)SnX(3)R'](+), as well as [YSnXR'](+), [M - CH(2)ph](+), XSn(+), (phCH(2))(3)Sn(+), phCH(2)Sn(+) (Y = &bond;CH(2)ph, X = &bond;OOCCH(2)OC(6)H(4)R(or C(6)H(3)R)) are detected in the positive mode. Water adduct ions are seen in both modes. The assignments are facilitated by agreement between observed and calculated isotopic patterns and tandem mass spectrometry studies.

Journal Article↗

Mass resolved MPI spectra of methyl iodide in the 430-490 nm region.

The mass resolved multiphoton ionization (MPI) spectra of methyl iodide were obtained in the 430-490 nm region using a time-of-flight (TOF) mass spectrometer. They have the same vibrational structure, which testifies that the fragment species, in the wavelength region under study, are from the photodissociation of multiphoton ionized molecular parent ions. Some features in the spectra are identified as three-photon excitations to 6p and 7s Rydberg states of methyl iodide. Two new vibrational structures of some Rydberg states are observed. The mechanism of ionization and dissociation is also discussed.

Hydrocarbons, Iodinated↗

Strong-light photoinhibition treatment accelerates the changes of protein secondary structures in triton-treated photosystem I and photosystem II complexes.

Changes in the protein secondary structure and electron transport activity of the Triton X-100-treated photosystem I (PSI) and photosystem II (PSII) complexes after strong illumination treatment were studied using Fourier transform-infrared (FT-IR) spectroscopy and an oxygen electrode. Short periods of photoinhibitory treatment led to obvious decreases in the rates of PSI-mediated electron transport activity and PSII-mediated oxygen evolution in the native or Triton-treated PSI and PSII complexes. In the native PSI and PSII complexes, the protein secondary structures had little changes after the photoinhibitory treatment. However, in both Triton-treated PSI and PSII complexes, short photoinhibition times caused significant loss of alpha-helical content and increase of beta-sheet structure, similar to the conformational changes in samples of Triton-treated PSI and PSII complexes after long periods of dark incubation. Our results demonstrate that strong-light treatment to the Triton-treated PSI and PSII complexes accelerates destruction of the transmembrane structure of proteins in the two photosynthetic membranes.

Electron Transport↗

The natural killer T-cell ligand alpha-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice.

Diabetes in non-obese diabetic (NOD) mice is mediated by pathogenic T-helper type 1 (Th1) cells that arise because of a deficiency in regulatory or suppressor T cells. V alpha 14-J alpha 15 natural killer T (NKT) cells recognize lipid antigens presented by the major histocompatibility complex class I-like protein CD1d (refs. 3,4). We have previously shown that in vivo activation of V alpha 14 NKT cells by alpha-galactosylceramide (alpha-GalCer) and CD1d potentiates Th2-mediated adaptive immune responses. Here we show that alpha-GalCer prevents development of diabetes in wild-type but not CD1d-deficient NOD mice. Disease prevention correlated with the ability of alpha-GalCer to suppress interferon-gamma but not interleukin-4 production by NKT cells, to increase serum immunoglobulin E levels, and to promote the generation of islet autoantigen-specific Th2 cells. Because alpha-GalCer recognition by NKT cells is conserved among mice and humans, these findings indicate that alpha-GalCer might be useful for therapeutic intervention in human diseases characterized by Th1-mediated pathology such as Type 1 diabetes.

Animals↗

Study of the absorption spectra of the 4f electron transitions of the praseodymium complex with ciprofloxacin and its analytical application.

Ciprofloxacin (CPFX) is proposed as a reagent for the derivative spectrophotometric determination of praseodymium in mixed rare earths. The absorption spectra of 4f electron transitions of the praseodymium complex with CPFX was studied by normal and derivative spectrophotometry. The stoichiometry of the praseodymium-CPFX complex was calculated by the molar ratio and continuous variations methods. A ratio of Pr to CPFX of 1:3 was found. The absorption bands of the 4f electron transitions of the complex were enhanced markedly. Using the third derivative spectrum. Beer's law was obeyed up to 35 microg cm(-3) of praseodymium. The relative standard deviation is 0.62% for 14 microg cm(-3) of praseodymium. The detection and quantification limits were 0.17 and 0.56 microg cm(-3) of praseodymium, respectively. A method for the direct determination of praseodymium in mixtures of rare earths with good accuracy and selectivity is described.

Journal Article↗

Speech processing strategy preferences among 55 European CLARION cochlear implant users.

This multicentre study investigates the preference and performance of a group of 55 adult CLARION cochlear implant users with the choice of simultaneous analogue stimulation (SAS) and continuous interleaved sampler (CIS) strategies during the first 3 months of implant use. Subjects were programmed with both strategies and instructed to use each of the two strategies in daily life to ascertain preference. Subjects were tested in both strategies with open-set sentence materials, auditory alone, at 2, 6 and 12 weeks after the initial programming session. Questionnaires were completed with preference ratings being recorded for the two strategies: 25% of subjects preferred SAS and 75% CIS. Subjects performed better in their strategy of choice. Preferences were set very early on in the process and did not change. Factors influencing preference are discussed. Offering the choice of fundamentally different strategies improves both individual and group performance.

Acoustic Stimulation↗

Monoclonal antibodies against human telomerase reverse transcriptase (hTERT): preparation, characterization, and application.

The catalytic subunit of human telomerase reverse transcriptase (hTERT), is the necessary and rate-limiting component to telomerase activation in cancer cells. To develop monoclonal antibodies (MAbs) against hTERT, a peptide-hTERT(9)-derived from specific motif T of hTERT was synthesized. Through fusion of splenocytes of BALB/c mice immunized with hTERT(9) with mouse myeloma cells, hybridomas were generated and clones secreting anti-hTERT(9) antibody were screened. After three rounds of limited dilution of candidate clones, three of which present stable and constant antibody production. The MAbs were hTERT(9)-specific and reactive with native hTERT of human cancer cells or tissues in Western blot and immunohistochemistry. The heavy chain variable regions from three hybridomas were cloned and sequenced confirming their mouse Ig derivation. The described investigation suggested that the generated MAbs to hTERT(9) could recognize native hTERT and be useful to cancer research.

Amino Acid Sequence↗

Genetic adaptive neural network to predict biochemical failure after radical prostatectomy: a multi-institutional study.

BACKGROUND AND PURPOSE: Despite many new procedures, radical prostatectomy remains one of the commonest methods of treating clinically localized prostate cancer. Both from the physician's and the patient's point of view, it is important to have objective estimation of the likelihood of recurrence, which forms the foundation for treatment selection for an individual patient. Currently, it is difficult to predict the probability of biochemical recurrence (rising serum prostate specific antigen [PSA] concentration) in an individual patient, and approximately 30% of the patients do experience recurrence. Tools predicting the recurrence will be of immense practical utility in the treatment selection and planning follow up. We have utilized preoperative parameters through a computer based genetic adaptive neural network model to predict recurrence in such patients, which can help primary care physicians and urologists in making management recommendations. PATIENTS AND METHODS: Fourteen hundred patients who underwent radical prostatectomy at participating institutions form the subjects of this study. Demographic data such as age, race, preoperative PSA, systemic biopsy based staging and Gleason scores were used to construct a neural network model. This model simulated the functioning of a trained human mind and learned from the database. Once trained, it was used to predict the outcomes in new patients. RESULTS: The patients in this comprehensive database were representative of the average prostate cancer patients as seen in USA. Their mean age was 68.4 years, the mean PSA concentration before surgery was 11.6 ng/mL, and 67% patients had a Gleason sum of 5 to 7. The mean length of follow-up was 41.5 months. Eighty percent of the cancers were clinical stage T2 and 5% T3. In our series, 64% of patients had pathologically organ-confined cancer, 33% positive margins, and 14% had seminal vesicle invasion. Lymph node positive patients were not included in this series. Progression as judged by serum PSA was noted in 30.6%. With entry of a few routinely used parameters, the model could correctly predict recurrence in 76% of the patients in the validation set. The area under the curve was 0.831. The sensitivity was 85%, the specificity 74%, the positive predictive value 77%, and the negative predictive value of 83%. CONCLUSION: It was possible to predict PSA recurrence with a high accuracy (76%). Physicians desiring objective treatment counseling can use this model, and significant cost savings are anticipated because of appropriate treatment selection and patient-specific follow-up protocols. This technology can be extended to other treatments such as watchful waiting, external-beam radiation, and brachytherapy.

Aged↗

Subcellular localization of the Iitracellular survival-enhancing Eis protein of Mycobacterium tuberculosis.

Mycobacterium tuberculosis is a facultative intracellular pathogen that has evolved the ability to survive and multiply within human macrophages. It is not clear how M. tuberculosis avoids the destructive action of macrophages, but this ability is fundamental in the pathogenicity of tuberculosis. A gene previously identified in M. tuberculosis, designated eis, was found to enhance intracellular survival of Mycobacterium smegmatis in the human macrophage-like cell line U-937 (J. Wei et al., J. Bacteriol. 182:377-384, 2000). When eis was introduced into M. smegmatis on a multicopy vector, sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the appearance of a unique 42-kDa protein band corresponding to the predicted molecular weight of the eis gene product. This band was electroeluted from the gel with a purity of >90% and subjected to N-terminal amino acid sequencing, which demonstrated that the 42-kDa band was indeed the protein product of eis. The Eis protein produced by M. tuberculosis H37Ra had an identical N-terminal amino acid sequence. A synthetic polypeptide corresponding to a carboxyl-terminal region of the deduced eis protein sequence was used to generate affinity-purified rabbit polyclonal antibodies that reacted with the 42-kDa protein in Western blot analysis. Hydropathy profile analysis showed the Eis protein to be predominantly hydrophilic with a potential hydrophobic amino terminus. Phase separation of M. tuberculosis H37Ra lysates by the nonionic detergent Triton X-114 revealed the Eis protein in both the aqueous and detergent phases. After fractionation of M. tuberculosis by differential centrifugation, Eis protein appeared mainly in the cytoplasmic fraction but also in the membrane, cell wall, and culture supernatant fractions as well. Forty percent of the sera from pulmonary tuberculosis patients tested for anti-Eis antibody gave positive reactions in Western blot analysis. Although the function of Eis remains unknown, evidence presented here suggests it associates with the cell surface and is released into the culture medium. It is produced during human tuberculosis infection and therefore may be an important M. tuberculosis immunogen.

Acetyltransferases↗

On the zeros of a third degree exponential polynomial with applications to a delayed model for the control of testosterone secretion.

In this paper, we first study the distribution of the zeros of a third degree exponential polynomial. Then we apply the obtained results to a delay model for the control of testosterone secretion. It is shown that under certain assumptions on the coefficients the steady state of the delay model is asymptotically stable for all delay values. Under another set of conditions, there is a critical delay value, the steady state is stable when the delay is less than the critical value and unstable when the delay is greater than the critical value. Thus, oscillations via Hopf bifurcation occur at the steady state when the delay passes through the critical value. Numerical simulations are presented to illustrate the results.

Animals↗

[The technical method for noninvasive magnetic stimulation of nerve center and its clinical application].

The increasing use of non-invasive magnetic stimulation technique for nerve center function examination and functional neuromuscular rehabilitation is a new cynosure in biomedical engineering and neuro-electrophysiologic researches. This paper analyzes theoretically the magnetic stimulation of first demonstration extending the technique model to human body, and the magnetic principle of physics. The characteristics of magnetic stimulation can be highlighted by comparing it to conventional electrical stimulation. Also presented are the peripheral multichannel magnetic stimulation to mimic electrical stimulation and the clinical functions toward neuromuscular rehabilitation.

Central Nervous System↗