The action of proteolytic enzymes on N,N-dimethyl proteins. Basis for a microassay for proteolytic enzymes.
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Biomedical subjects
Publications and source records attributed to Y Lin.
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The large and growing body of experimental data on molecular binding is of enormous value in biology, pharmacology, and chemistry. Applications include the assignment of function to biomolecules, drug discovery, molecular modeling, and nanotechnology. However, binding data are difficult to find and access because they are available almost exclusively through scientific journals. BindingDB, a public, web-accessible database of measured binding affinities, is designed to address this problem. BindingDB collects data for natural and modified biomolecules and for synthetic compounds, and provides detailed experimental information. Currently, measurements by isothermal titration calorimetry are fully supported; measurements by enzyme inhibition will soon be included as well. The web site allows data to be searched by a range of criteria, including binding thermodynamics, sequence homology, and chemical structure, substructure, and similarity. Experimentalists are encouraged to publicize their data by entering it into BindingDB via the online forms. Such data can be updated or revised by the depositor, if necessary, and will remain publicly accessible. User involvement and feedback are welcomed.
DNA vaccination with the plasmid expressing Japanese encephalitis virus (JEV) nonstructural protein 1 (pJNS1) has been shown to induce effective immunity against JEV infection. To further increase the efficacy of pJNS1 DNA vaccination, we coinjected pJNS1 with a plasmid that expresses heat shock protein 70.1 (pHSP70.1) into mice. We found that coinjection of pHSP70.1 enhanced both T cell proliferation and cytotoxic effects, but not the antibody response to JEV. Moreover, mice immunized with both pHSP70.1 and pJNS1 were resistant to lethal challenges of JEV, indicating that the protective immunity against JEV is not decreased, in spite of the low antibody titer via the immunization of pHSP70.1. Since DNA vaccination administered by pJNS1 did not elicit strong cellular immunity in our previous study, the administration of pHSP70.1 apparently could be used as an adjuvant to enhance cell-mediated immunity in this model system. Thus, coadministration of pHSP70.1 DNA with plasmid DNA encoding tumor- or virus-specific antigens might be very useful in the treatment of cancers and other infectious diseases.
Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon soft tissue tumors. In children with neurofibromatosis 1 (NF1), a MPNST often arises in a pre-existing neurofibroma, or may represent an initial manifestation without other obvious stigmata of the disease. The development of MPNSTs may be associated with instability of the p53 tumor suppressor gene since it is the most frequent genetic abnormality in soft tissue sarcomas. To assess the presence of p53 accumulation in MPNSTs and its correlation with clinical and pathologic features, we studied 12 neurofibromas (NFs), including 4 tumors with cellular features (one congenital) and 10 MPNSTs. Six MPNSTs were associated with NF1, all of which developed within a plexiform neurofibroma. Cell proliferation evaluated with an antibody to Ki-67 and nuclear p53 staining were both detected by immunohistochemistry. We found p53 positivity in 60% of MPNSTs. All NFs except the congenital tumor were p53 immunonegative (P < 0.01). Rare p53-positive nuclei were detected in the transitional zone in two of six MPNSTs arising in plexiform NFs. Ki-67 distinguished the NFs from MPNSTs (P < 0.005). Half of the NF1 patients with p53-positive MPNSTs developed recurrence or metastases or developed a second malignancy within 2 years of diagnosis, whereas patients with p53-positive sporadic MPNSTs were free of disease 1 to 7 years later. We found p53 accumulation more frequently in NF1-associated MPNSTs. p53 mutations may be an additional biologic factor to account for the poor prognosis in these tumors.
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A novel tracer technique is presented for the simultaneous and independent measurement of multiple stable isotopically labeled essential fatty acids. Gas chromatography/negative chemical ionization mass spectrometry was employed for high sensitivity detection of the following isotopes: deuterium-labeled-linolenate, carbon-13-U-labeled-eicosapentaenoate, carbon-13-U-labeled-linoleate, and deuterium-labeled-dihomo-gamma-linolenate. These isotope-labeled fatty acids in vehicle oil were given to rats either singly or together as a single oral dose. Rat blood was collected after dosing and the isotopomers of the precursors and their main metabolites, including those containing both(13) C and (2)H, were detected simultaneously with good resolution and without interference from other isotopes due to differences in mass and chromatographic retention.
In the recent years, functional electrical stimulation has been applied to restore impaired motility in the gastrointestinal tract. Unlike other methods of electrical stimulation of the gut, microprocessor-controlled, sequential electrical stimulation has been shown to induce peristalsis and enhance emptying in acute canine gastric and colonic models. This study aims at completing the development of a portable microprocessor-based functional stimulator system consisting of a microelectronic stimulator, patient-specific computer-based real-time software and a programming interfacing device. The ultimate goals of the design are to ensure that (1) the portable stimulator can be efficiently utilized in chronic animal experiments; and (2) the device can be further miniaturized into an implantable version. The designed portable stimulator generates four channel sequential bipolar rectangular pulse trains with programmable parameters within the stimulation requirements obtained from a previously developed computer model. Real-time simulation of colonic peristalsis and a case-specific stimulation model were implemented using patient-specific computer-based software. A chronic canine case study confirmed the feasibility of this microprocessor-controlled stimulation method for future clinical applications in humans.
A new triterpene glycoside, rollentoside A, has been isolated from Asterias rollentoni Bell and identified as 3beta-O-{3-O-methyl-beta-D-xylopyranosyl-(1-->3)-O-beta-D-glucopyranosyl-(1-->4)-O-beta-D-quinopyranosyl-(1-->2)-O-beta-D-xylopyranosyl}-16-beta-acetoxy-23S-acetoxy-holost-7-ene (1), together with a new natural product, rollentoside B (2). The structures of compounds1 and 2 were elucidated by extensive 1D and 2D NMR investigation (1H-1H COSY, TOCSY, HSQC, HMBC, NOESY).