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Biomedical subjects

S Wang

Publications and source records attributed to S Wang.

At least 685 records · Page 38Linked to original sources
PubMed1999

Direct identification of ventrointermediate nucleus of the thalamus on magnetic resonance and computed tomography images.

OBJECTIVE: The ventro-intermediate (Vim) nucleus of the thalamus is a commonly used target for the treatment of tremor. The thalamic fasciculus contains myelinated fibers, believed to play a role in the generation of tremor, that converge into a dense bundle at the inferior aspect of the Vim nucleus, making it visible on magnetic resonance (MR) and computed tomography (CT) images. This structure, therefore, can be visualized directly and targeted for thalamotomy. METHODS: Thalamotomies were performed on nine patients (who have a follow-up of 13-23 months) with parkinsonian and essential tremors using MR and CT images. The tremor target was hypointense on MR images obtained in inversion recovery sequence and hypointense on CT images. It was therefore visualized, directly targeted, and probed. Stimulation studies were done to physiologically confirm accuracy of the probe placement and then a radiofrequency lesion was made. RESULTS: Stimulation of the target identified as the Vim nucleus on MR and CT images produced responses similar to those expected from the Vim nucleus. After this site was lesioned tremor disappeared in all nine patients. CONCLUSION: The Vim nucleus of the thalamus is visible on MR and CT images. Destruction of this target abolishes parkinsonian and essential tremors.

Aged↗
PubMed1999

Extracellular matrix protein-induced changes in human salivary epithelial cell organization and proliferation on a model biological substratum.

We have used a denuded rat tracheal preparation as a biological substratum on which to examine the growth and morphology of a salivary epithelial cell line (HSG) in vitro. In the absence of an additional coating of matrix proteins, HSG cells grew at low density on tracheae. Coating the tracheae with Vitrogen (a commercial collagen I preparation) or fibronectin promoted HSG cell growth and monolayer formation. Conversely, if a coating of Matrigel was applied, cells grew in a more organized fashion, but at low density. Generally similar results were obtained with cells grown on laminin and collagen IV but with less organization. These studies demonstrate the utility of a natural, tubular substratum for testing the influence of different matrix proteins on salivary epithelial cell behavior.

Animals↗
PubMed1999

Capability of serum to convert streptomycin to cytotoxin in patients with aminoglycoside-induced hearing loss.

Individual variations in sensitivity to the ototoxic effects of aminoglycoside antibiotics are well documented. Our research demonstrates that there is an apparent difference in serum from patients who are resistant or susceptible to aminoglycoside ototoxicity. In the first study, the cytotoxicity of sera from patients with and without hearing loss after various time periods following the discontinuation of aminoglycoside treatment was assayed using the isolated outer hair cell toxicity assay. The results indicate that sera from patients with hearing loss were significantly more toxic than sera from patients with normal hearing or minimal hearing loss. This toxicity may persist for up to 1 year after discontinuation of aminoglycoside therapy. In a second study, sera were obtained from patients who had received aminoglycoside therapy several years previously. None of these sera was toxic to isolated outer hair cells in vitro. Streptomycin was then incubated with the sera or a protein fraction isolated from sera, and the incubation mixtures were tested for toxicity. The percentage of damaged outer hair cells was significantly higher when streptomycin had been treated with sera or a serum protein fraction from patients with hearing loss (58+/-10% and 68+/-9%, respectively) than with sera or a serum protein fraction from a control group (10+/-5% and 17+/-4%, respectively). In addition, several incubation mixtures were analyzed using high performance liquid chromatography. A new chromatographic peak was only found in the incubations of streptomycin with serum protein from patients with hearing loss. The results suggest that sera from individuals sensitive to aminoglycoside antibiotics may metabolize these drugs to cytotoxins.

Adolescent↗
PubMed1999

Receptor-mediated targeting of 67Ga-deferoxamine-folate to folate-receptor-positive human KB tumor xenografts.

The radiochemical synthesis and stability of 67Ga-deferoxamine-folate ([67Ga]Ga-DF-Folate) were examined as a function of DF-Folate concentration. Optimal labeling occurred at DF-Folate concentrations > or =2.5 microg/mL. To define the possible biological significance of variations in product formulation, the biodistribution of [67Ga]Ga-DF-Folate was examined as a function of administered deferoxamine-folate dose in an athymic mouse KB tumor model. The folate-receptor-positive KB tumors were found to concentrate the 67Ga radiolabel in a dose-dependent fashion, consistent with saturable involvement of the folate receptor in mediating tumor accumulation of the radiopharmaceutical.

Animals↗
PubMed1999

Simple single-section method for measurement of left and right atrial volumes with electron-beam CT.

RATIONALE AND OBJECTIVES: The authors estimated left and right atrial volumes by using a simple method of measurement with nonenhanced electron-beam computed tomography (CT). MATERIALS AND METHODS: One hundred sixty-four contrast material-enhanced electron-beam CT studies were divided into two groups. Group 1, which included 104 studies, was used to develop the measurement method (i.e., the formulas) for measuring left and right atrial volumes from a nonenhanced study. Group 2 consisted of 60 studies on which the validity of the method was tested. Measurement of left and right atrial volumes was performed on all section levels by tracing the respective atrial borders for each section, then multiplying the area by section thickness and summing the resultant volumes. RESULTS: Calculated left and right atrial volumes were derived by using the biggest atrial area and cephalic-caudal span. The span was equal to section thickness times the number of sections in which the atria were present. Linear regression analysis formulas were acquired with the biggest atrial area and cephalic-caudal span. Left and right atrial calculated volumes were obtained with these formulas and demonstrated a significant good relation (r > .95, P < .001) and a difference of less than 11% (P < .05) in absolute values between measured and calculated volumes. Intraobserver, interobserver, and interstudy reproducibility were excellent, with less than 10% difference in absolute values. CONCLUSION: Left and right atrial volumes can be accurately estimated from a single midventricular section by using nonenhanced electron-beam CT.

Anatomy, Cross-Sectional↗
PubMed1999

Isolation of a mutant of Kluyveromyces sp. Y-85 resistant to catabolite repression.

The production of inulinase in Kluyveromyces sp. Y-85 is repressed by the carbon catabolites. To screen for derepression mutants, the strain of Kluyveromyces sp. Y-85 was treated with the mutagenic agent, ethyl methane sulfonate (EMS). Initially, mutants resistant to catabolite repression by 2-deoxy-D-glucose were isolated. One such mutant, Kluyveromyces sp. Y-85 K6, was found to exhibit stable, 2-fold higher expression of inulinase than the wild-type in glucose-containing medium, indicating that it is a promising strain for industrial production.

Journal Article↗
PubMed1999

A potential mechanism for selective control of cap-independent translation by a viral RNA sequence in cis and in trans.

Highly efficient cap-independent translation initiation at the 5'-proximal AUG is facilitated by the 3' translation enhancer sequence (3'TE) located near the 3' end of barley yellow dwarf virus (BYDV) genomic RNA. The role of the 3'TE in regulating viral translation was examined. The 3'TE is required for translation and thus replication of the genomic RNA that lacks a 5' cap (Allen et al., 1999, Virology253:139-144). Here we show that the 3'TE also mediates translation of uncapped viral subgenomic mRNAs (sgRNA1 and sgRNA2). A 109-nt viral sequence is sufficient for 3'TE activity in vitro, but additional viral sequence is necessary for cap-independent translation in vivo. The 5' extremity of the sequence required in the 3' untranslated region (UTR) for cap-independent translation in vivo coincides with the 5' end of sgRNA2. Thus, sgRNA2 has the 3'TE in its 5' UTR. Competition studies using physiological ratios of viral RNAs showed that, in trans, the 109-nt 3'TE alone, or in the context of 869-nt sgRNA2, inhibited translation of genomic RNA much more than it inhibited translation of sgRNA1. The divergent 5' UTRs of genomic RNA and sgRNA1 contribute to this differential susceptibility to inhibition. We propose that sgRNA2 serves as a novel regulatory RNA to carry out the switch from early to late gene expression. Thus, this new mechanism for temporal control of translation control involves a sequence that stimulates translation in cis and acts in trans to selectively inhibit translation of viral mRNA.

3' Untranslated Regions↗
PubMed1999

Analysis of Probe-Sample Interaction in Near-field Optical Image of Dielectric Structures.

: A two-dimensional formalism is provided for analyzing the probe-sample interaction of optical near-field images in transmission mode. The numerical simulation is performed on a dielectric surface with sub-wavelength structures. The constant-height, near-field intensity through two Gaussian ridges has been calculated for p-polarized incident light. The influence on the signal by the dielectric function of the probe, the size of the scatterers, and the angle of incidence is investigated. The passive probe model is compared when equipped with and without the tip and the near-field intensity is simultaneously calculated.

Journal Article↗
PubMed1999

Development of a compound-specific ELISA for flufenoxuron and an improved class-specific assay for benzoylphenylurea insect growth regulators.

This study describes immunochemical approaches for the compound-specific detection of flufenoxuron and class-specific detection of benzoylphenylurea (BPU) insecticides. With the aim of developing a highly specific immunoassay for flufenoxuron, a hapten was synthesized by introducing a spacer arm at the 2,6-difluoro substituent aromatic ring of a flufenoxuron derivative. An IC(50) value of 2.4 ppb was obtained for flufenoxuron, with detection of the other four BPUs being more than 4000-fold less sensitive. For the development of class-specific ELISA for five BPUs, a new approach was used for the hapten preparation in which a butanoic acid linkage was introduced into the 3,5-dichloro-substituted aniline ring of chlorfluazuron analogue. Although the resultant ELISA still exhibited slightly differing cross-reactions for these five BPUs, this method had broader specificity than the previously reported polyclonal antibody-based ELISA. Spike and recovery studies for five BPUs in soil and water indicated that both the compound- and class-specific ELISAs were able to quantitatively detect BPU residues in soil and water. This study also provided additional insights into the influence of the immunizing hapten structure on the specificities of the antibodies obtained.

Animals↗
PubMed1999

Stereochemistry of the roridins. Diastereomers of roridin E.

A careful investigation of cultures of Myrothecium verrucaria has shown that this fungus produces all four roridin E isomers (3a-d), diastereomeric at the C-6' and C-13' centers. The stereochemistries at these centers were established by a combination of X-ray crystallographic analysis, NMR spectroscopy, and chemical transformations. NMR data from these and other macrocyclic trichothecenes allows for the assignment of configurations at the C-6' and C-13' centers for most of these compounds, the exceptions being those congeners having a C-4' ketone group in the macrolide ring.

Crystallography, X-Ray↗
PubMed1999

Single-chain 434 repressors with altered DNA-binding specificities. Isolation of mutant single-chain repressors by phenotypic screening of combinatorial mutant libraries.

Combinatorial mutant libraries of the single-chain 434 repressor were used to discover novel DNA-binding specificities. Members of the library contain one wild type domain and one mutant domain which are connected by a recombinant peptide linker. The mutant domain contains randomized amino acids in place of the DNA-contacting residues. The single-chain derivatives are expected to recognize artificial operators containing the DNA sequence of ACAA--6 base-pairs--NNNN, where ACAA is bound by the wild-type and NNNN by the mutant domain. An in vivo library screening method was used to isolate mutant DNA-binding domains which recognize the TTAA site of an asymmetric operator. Several mutants showed high affinity binding to the selection target and also strong (up to 80 fold) preference for TTAA over the wild type TTGT sequence. Some of the isolated mutants bound with very high affinities (10-50 pM) to operators containing the TTAC sequence, a close homologue of the TTAA selection target.

Base Sequence↗
PubMed1999

Antioxidant properties of aspirin: characterization of the ability of aspirin to inhibit silica-induced lipid peroxidation, DNA damage, NF-kappaB activation, and TNF-alpha production.

Electron spin resonance (ESR) was used to investigate the reaction of aspirin toward reactive oxygen species, such as hydroxyl radicals (*OH), superoxide radicals (O2-) and H2O2. The Fenton reaction (Fe(II) + H2O2 ---> FE(III) + *OH + OR) was used as a source of *OH radicals. The results show that aspirin is an efficient *OH radical scavenger with a reaction rate constant of k = 3.6 x 10(10) M(-1) sec(-1), which is faster than several well established antioxidants, such as ascorbate, glutathione and cysteine. However, aspirin is not a good scavenger for O2- or H2O2. Through its antioxidant property, aspirin exhibited a protective effect against silica-induced lipid peroxidation and DNA strand breakage. Aspirin also inhibited the activation of nuclear transcription factor-kappaB induced by silica, lipopolysaccharide or the transition metal, Fe(II), as demonstrated by electrophoretic mobility shift assay. The results show that aspirin functions as an antioxidant via its ability to scavenge *OH radicals. This antioxidant property may explain some of its various physiological and pharmacological actions.

Animals↗
PubMed1999

MCDOCK: a Monte Carlo simulation approach to the molecular docking problem.

Prediction of the binding mode of a ligand (a drug molecule) to its macromolecular receptor, or molecular docking, is an important problem in rational drug design. We have developed a new docking method in which a non-conventional Monte Carlo (MC) simulation technique is employed. A computer program, MCDOCK, was developed to carry out the molecular docking operation automatically. The current version of the MCDOCK program (version 1.0) allows for the full flexibility of ligands in the docking calculations. The scoring function used in MCDOCK is the sum of the interaction energy between the ligand and its receptor, and the conformational energy of the ligand. To validate the MCDOCK method, 19 small ligands, the binding modes of which had been determined experimentally using X-ray diffraction, were docked into their receptor binding sites. To produce statistically significant results, 20 MCDOCK runs were performed for each protein-ligand complex. It was found that a significant percentage of these MCDOCK runs converge to the experimentally observed binding mode. The root-mean-square (rms) of all non-hydrogen atoms of the ligand between the predicted and experimental binding modes ranges from 0.25 to 1.84 A for these 19 cases. The computational time for each run on an SGI Indigo2/R10000 varies from less than 1 min to 15 min, depending upon the size and the flexibility of the ligands. Thus MCDOCK may be used to predict the precise binding mode of ligands in lead optimization and to discover novel lead compounds through structure-based database searching.

Binding Sites↗
PubMed1999

Signals in stochastically generated neurons.

To incorporate variation of neuron shape in neural models, we developed a method of generating a population of realistically shaped neurons. Parameters that characterize a neuron include soma diameters, distances to branch points, fiber diameters, and overall dendritic tree shape and size. Experimentally measured distributions provide a means of treating these morphological parameters as stochastic variables in an algorithm for production of neurons. Stochastically generated neurons shapes were used in a model of hippocampal dentate gyrus granule cells. A large part of the variation of whole neuron input resistance R(N) is due to variation in shape. Membrane resistivity Rm computed from R(N) varies accordingly. Statistics of responses to synaptic activation were computed for different dendritic shapes. Magnitude of response variation depended on synapse location, measurement site, and attribute of response.

Algorithms↗
PubMed1999

Proximal impact of two first-grade preventive interventions on the early risk behaviors for later substance abuse, depression, and antisocial behavior.

We assessed the immediate effects of two universal, first-grade preventive interventions on the proximal targets of poor achievement, concentration problems, aggression, and shy behaviors, known early risk behaviors for later substance use/abuse, affective disorder, and conduct disorder. The classroom-centered (CC) intervention was designed to reduce these early risk behaviors by enhancing teachers' behavior management and instructional skills, whereas the family-school partnership (FSP) intervention was aimed at improving parent-teacher communication and parental teaching and child behavior management strategies. Over the course of first and second grades, the CC intervention yielded the greatest degree of impact on its proximal targets, whereas the FSP's impact was somewhat less. The effects were influenced by gender and by preintervention levels of risk. Analyses of implementation measures demonstrated that greater fidelity to the intervention protocols was associated with greater impact on behavior ratings and on achievement scores, thus providing some evidence of specificity in the effect of the interventions.

Baltimore↗
PubMed1999

Bryostatin 1 enhances paclitaxel-induced mitochondrial dysfunction and apoptosis in human leukemia cells (U937) ectopically expressing Bcl-xL.

The effects of the protein kinase C (PKC) activator and down-regulator bryostatin 1 were examined with respect to paclitaxel-induced apoptosis and antiproliferative activity in human myeloid leukemia cells (U937) displaying enforced expression of the anti-apoptotic protein Bcl-xL. Overexpression of Bcl-xL blocked various aspects of paclitaxel-mediated apoptosis, including caspase-3 activation, degradation of poly(ADP-ribose) polymerase (PARP), loss of mitochondrial membrane potential (Delta Psim), and release of cytochrome c. However, subsequent (but not prior) exposure of paclitaxel-treated U937/Bcl-xL cells (500 nM; 6 h) to bryostatin 1 (10 nM; 15 h) restored the extent of apoptosis, caspase activation, and mitochondrial damage to levels approximating those in paclitaxel-treated empty-vector control cells (U937/Neo). Potentiation of paclitaxel-induced apoptosis by bryostatin 1 in U937/Bcl-xL cells occurred primarily in the G2M cell population, and was associated with alterations in Bcl-xL gel mobility and a reduction in paclitaxel-mediated stimulation of CDK1 activity. Enhancement of paclitaxel-induced apoptosis by bryostatin 1 in Bcl-xL overexpressors was accompanied by a corresponding reduction in clonogenic potential. In contrast to its effects on apoptosis, bryostatin 1 failed to restore paclitaxel-mediated increases in free Bax levels in U937/Bcl-xL cells. Lastly, the actions of bryostatin 1 were mimicked by a pharmacologic inhibitor of the MEK1/MAP kinase pathway (PD98059), but not by SB203580, an inhibitor of p 38 MAP kinase. Moreover, sequential exposure of both U937/Neo or/Bcl-xL cells to paclitaxel followed by bryostatin 1 or PD98059 was associated with a net reduction in MAP kinase activity. Collectively, these findings indicate that protection against paclitaxel-mediated mitochondrial dysfunction and apoptosis in human U937 leukemia cells conferred by Bcl-xL overexpression can be substantially overcome by bryostatin 1 and possibly other agents that interrupt the MAP kinase signal transduction pathway.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Systemic mycobacterial infection inhibits antigen-specific immunoglobulin E production, bronchial mucus production and eosinophilic inflammation induced by allergen.

As the burden of infectious diseases becomes reduced in many countries, a remarkable increase in the incidence of allergies has occurred. The basis for the rise in atopic disorders as a correlate of the decline in infectious diseases has not been defined. In the present study, we tested experimentally whether prior systemic infection with Mycobacterium bovis bacillus Calmette Guérin (BCG) had any effect on ovalbumin (OVA) Al(OH)3 (alum)-induced immunoglobulin E (IgE) production, airway mucus production and eosinophilic inflammation. The data showed that allergen-specific IgE production and OVA-induced eosinophilia and goblet cell development were significantly inhibited by prior infection with BCG. Correspondingly, following immunization with OVA alum, BCG-infected mice exhibited significantly higher levels of allergen-driven interferon-gamma (IFN-gamma) production than the mice without infection. The ratio of IFN-gamma: interleukin (IL)-4 production was higher in OVA-sensitized mice with prior BCG infection than in those without infection. The abrogation of OVA-induced mucus production and pulmonary eosinophilia in BCG-infected mice correlated with significantly decreased IL-5 production and increased IFN-gamma and IL-12 production. These data provide direct evidence that intracellular bacterial infection (i.e. BCG) can inhibit antigen-specific IgE and airway reactivity induced by environmental allergen. Furthermore, the results suggest that changes in cytokine-producing patterns of T lymphocytes and other cells may be the mechanism by which infections influence allergies.

Allergens↗