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B Lin

Publications and source records attributed to B Lin.

At least 109 records · Page 6Linked to original sources
PubMed1999

Separation of drugs by capillary electrophoresis, Part 10. Permethyl-alpha-cyclodextrin as chiral solvating agent.

Following the German-Chinese Drug Screening Program, 86 racemic drugs were investigated in capillary zone electrophoresis in the presence of the chiral solvating agent (CSA) hexakis-(2,3,6-tri-O-methyl)-alpha-cyclodextrin (TM-alpha-CD). Of the 86 drugs, 23 were separated into enantiomeric pairs. A comparison of the migration separation factors (alpha(m)) and the migration retardation factors (Rm) with previously published data for native alpha-CD revealed that the 'upper-rim' hydroxyl groups do not necessarily facilitate the recognition of the drug enantiomers by the chiral host. In contrast, an overall increase in affinity for the permethylated host led to a higher rate of successful enantiomer separations. A key substructure (4H) was identified in the analyte structure domain, with a crucial influence on the behavior of a particular drug.

Cyclodextrins↗
PubMed1999

Study of interaction between drug enantiomers and serum albumin by capillary electrophoresis.

The interaction between drugs and human serum albumin (HSA) was investigated by capillary electrophoresis (CE). It involves stereoselectivity, drug displacement and synergism effects. Under protein-drug binding equilibrium, the unbound concentrations of drug enantiomers were measured by frontal analysis (FA). The stereoselectivity of verapamil (VER) binding to HSA was proved by the different free fractions of two enantiomers. In physiological pH (7.4, ionic strength 0.17 phosphate buffer) when 300 microM (+/-) VER were equilibrated with 500 microM HSA, the concentration of unbound S-VER was about 1.7 times its antipode. The binding constants of two enantiomers, K(R-VER) and K(S-VER), were 2670 and 850 M(-1), respectively. However, no obvious stereoselective binding of propranolol (PRO) to HSA was observed. Trimethyl-beta-cyclodextrin (45 mM) was used as a chiral selector in pH 2.5 phosphate buffer. Several drug systems were studied by the method. When ibuprofen (IBU) was added into VER-HSA solution. R-VER was partially displaced while S-VER was not displaced at all. A binding synergism effect between bupivacaine (BUP) and verapamil was observed and further study suggested that verapamil and bupivacaine occupy different binding site of HSA (site II and site III, respectively).

Binding, Competitive↗
PubMed1999

Progressive parenchymal deposition of beta-amyloid precursor protein in rat brain following global cerebral ischemia.

In addition to producing acute neuronal necrosis within selectively vulnerable brain regions, our recent studies have shown that global cerebral ischemia may also be followed by protracted degenerative changes occurring over the course of 10 weeks. Chronic brain pathology may be associated with the abnormal deposition of beta-amyloid precursor protein (betaAPP). In the present study, we used a monoclonal antibody to the N-terminal portion of betaAPP to characterize the brains of rats surviving 1-10 weeks following 10 min of global brain ischemia produced by bilateral carotid artery occlusions plus systemic hypotension. After ischemia, increased betaAPP immunolabeling emerged in several brain regions. In the hippocampus, granular deposits appeared in the damaged CA1 area by 2 weeks, and by 4-10 weeks the remnants of necrotic CA1 neurons were also immunolabeled. In striatum and thalamus, regions with necrotic cell death also revealed granular betaAPP deposits. The neocortex was devoid of overt ischemic neuronal damage but revealed prominent betaAPP immunoreactivity. Large ovoid deposits of low-density betaAPP immunostaining occurred in cortical neurons at 1-2 weeks. At 4-10 weeks, large round or oval deposits immunoreactive for betaAPP appeared in several cortical regions. The highest density of deposits was seen in the temporal and piriform cortices. Our results indicate that abnormal betaAPP deposition may result from ischemic as well as chronic neurodegenerative processes.

Amyloid beta-Protein Precursor↗
PubMed1999

Type-1c glycogen storage disease is not caused by mutations in the glucose-6-phosphate transporter gene.

Glycogen storage disease type 1 (GSD-1) is a group of autosomal recessive disorders caused by deficiencies in glucose-6-phosphatase (G6Pase) and the associated substrate/product transporters. Molecular genetic studies have demonstrated that GSD-1a and GSD-1b are caused by mutations in the G6Pase enzyme and a glucose-6-phosphate transporter (G6PT), respectively. While kinetic studies of G6Pase catalysis predict that the index GSD-1c patient is deficient in a pyrophosphate/phosphate transporter, the existence of a separate locus for GSD-1c remains unclear. We have previously shown that the G6Pase gene of the index GSD-1c patient is intact; we now show that the G6PT gene of this patient is normal, strongly suggesting the existence of a distinct GSD-1c locus.

Antiporters↗
PubMed1999

NF-kappaB functions as both a proapoptotic and antiapoptotic regulatory factor within a single cell type.

Recently NF-kappaB has been shown to have both proapoptotic and antiapoptotic functions. In T cell hybridomas, both T cell activators and glucocorticoids induce apoptosis. Here we show that blockade of NF-kappaB activity, using a dominant negative IkappaBalpha, has opposite effects on these two apoptotic signals. Treatment with PMA plus ionomycin (P/I) results in the upregulation of Fas Ligand (FasL) and induction of apoptosis. Inhibition of NF-kappaB activity inhibits the P/I mediated induction of FasL mRNA and decreases the level of apoptosis in these cultures, thus establishing NF-kappaB as a proapoptotic factor in this context. Conversely, inhibition of NF-kappaB confers a tenfold increase in glucocorticoid mediated apoptosis, establishing that NF-kappaB also functions as an antiapoptotic factor. We conclude that NF-kappaB is a context-dependent apoptosis regulator. Our data suggests that NF-kappaB may function as an antiapoptotic factor in thymocytes while functioning as a proapoptotic factor in mature peripheral T cells.

Apoptosis↗
PubMed1999

Geometrical and wave optics of paraxial beams.

Most calculational techniques used to evaluate beam propagation are geared towards either fully coherent or fully incoherent beams. The intermediate partial-coherence regime, while in principle known for a long time, has received comparably little attention so far. The resulting shortage of adequate calculational techniques is currently being felt in the realm of x-ray optics where, with the advent of third generation synchrotron light sources, partially coherent beams become increasingly common. The purpose of this paper is to present a calculational approach which, utilizing a "variance matrix" representation of paraxial beams, allows for a straightforward evaluation of wave propagation through an optical system. Being capable of dealing with an arbitrary degree of coherence, this approach covers the whole range from wave to ray optics, in a seamless fashion.

Journal Article↗
PubMed1999

The Caulobacter crescentus CgtA protein displays unusual guanine nucleotide binding and exchange properties.

The Caulobacter crescentus CgtA protein is a member of the Obg-GTP1 subfamily of monomeric GTP-binding proteins. In vitro, CgtA specifically bound GTP and GDP but not GMP or ATP. CgtA bound GTP and GDP with moderate affinity at 30 degrees C and displayed equilibrium binding constants of 1.2 and 0.5 microM, respectively, in the presence of Mg(2+). In the absence of Mg(2+), the affinity of CgtA for GTP and GDP was reduced 59- and 6-fold, respectively. N-Methyl-3'-O-anthranoyl (mant)-guanine nucleotide analogs were used to quantify GDP and GTP exchange. Spontaneous dissociation of both GDP and GTP in the presence of 5 to 12 mM Mg(2+) was extremely rapid (k(d) = 1.4 and 1.5 s(-1), respectively), 10(3)- to 10(5)-fold faster than that of the well-characterized eukaryotic Ras-like GTP-binding proteins. The dissociation rate constant of GDP increased sevenfold in the absence of Mg(2+). Finally, there was a low inherent GTPase activity with a single-turnover rate constant of 5.0 x 10(-4) s(-1) corresponding to a half-life of hydrolysis of 23 min. These data clearly demonstrate that the guanine nucleotide binding and exchange properties of CgtA are different from those of the well-characterized Ras-like GTP-binding proteins. Furthermore, these data are consistent with a model whereby the nucleotide occupancy of CgtA is controlled by the intracellular levels of guanine nucleotides.

Bacterial Proteins↗
PubMed1999

Nursing information systems: a survey of current practices.

This article reports the results of a recent survey on usefulness of computer-based nursing information systems (NISs). To assess their usefulness, three research questions were asked: Are computer-based NISs useful to most nurses? What accounts for the nurses' assessment of NISs? What factors influence the usefulness of NISs? This framework can serve to guide empirical investigations into various aspects of information systems in hospitals. The findings lead to implications for nursing care management, as well as suggestions for nursing quality research opportunities.

Attitude of Health Personnel↗
PubMed1999

[Temperature effect and temperature gradient technology in capillary electrophoresis].

A review is given here to describe the temperature effect and temperature gradient technology in capillary electrophoresis (CE). The temperature effects on the analysis of DNA, protein peptides and amino acids, enantiomers, carbohydrates and other substances are discussed respectively. The theory of temperature effect is also mentioned. The importance of the temperature gradient in CE, the classifications of gradient technology in CE, the potential applications and different method development of the temperature gradient are described. Fifty-one references are cited.

Amino Acids↗
PubMed1999

[Investigation of association parameters of basic drugs to human serum albumin by capillary zone electrophoresis/frontal analysis].

A CZE/FA method was applied to the study of association parameters of basic drugs, verapamil (VER) and propranolol (PRO), to human serum albumin (HSA) under drug-HSA association equilibria. After the direct hydrodynamic injection of a drug-HSA mixed solution into a coated capillary (effective length, 32 cm; 50 microns i.d.), the basic drug is eluted as a zonal peak with a plateau region under condition of phosphate buffer (pH 7.4, ionic strength = 0.17) at 10 kV running voltage. The unbound concentration of drug can be determined from the plateau peak height with good linear response, r = 0.999 for both VER(n = 6) and PRO(n = 8), respectively. Six VER-HSA solutions (containing 50-175 mumol/L of VER and 450-325 mumol/L of HSA) and eight PRO-HSA solutions (containing 50-400 mumol/L of VER and 450-100 mumol/L of HSA) were investigated. Three analytical methods were used for the present CZE/FA system including Scatchard, Klotz and non-linear regression analyses. The estimated association parameters were as follows: the numbers of HSA binding site n for VER were over 1.21(0.04)-1.30(0.09), binding constant, K, was between 1,690(130) and 1,790(70). Whereas for PRO, n = 0.54(0.04)-0.62(0.03), and K = 1,390(70)-1,690(180). The data deduced from these three analyses agreed well with each other.

Drug Interactions↗
PubMed1999

[Intersection point rule for the retention value with mobile phase composition and boiling point of the homologues and chlorobenzenes in soil leaching column chromatography].

Based on the linear retention equation of the logarithm of the capacity factor (logk') vs. the methanol volume fraction (psi) of aqueous binary mobile phase in soil leaching column chromatography, the intersection point rule for the logk' of homologues and weak polar chlorobenzenes, with psi, as well as with boiling point, has been derived due to existence of the similar interactions among solutes of the same series, stationary phase (soil) and eluent (methanol-water). These rules were testified by experimental data of homologues (n-alkylbenzenes, methylbenzenes) and weak polar chlorobenzenes.

English Abstract↗
PubMed1999

[Albumin-drug binding study by capillary electrophoresis. I. Quantitative applicability examination of liquid pre-column].

To measure the free concentration of verapamil (a basic drug) enantiomers in the binding system of human serum albumin(HSA), a capillary electrophoretic method, liquid precolumn(LCP), was established, and the method was examined systematically. In physiological pH condition (pH 7.4, ionic strength 0.17), HSA migrates in the opposite direction of verapamil. This electrophoretic property basically supposed the probability of preventing HSA from entering the capillary whereas a positive electric field was used. Finally, the drug enantiomers were separated by the chiral selector (45 mmol/L trimethyl-beta-cyclodextrin, pH 2.5 phosphate buffer) and the free concentration of each optical isomer in the binding system was measured. Seven samples were examined and their relative standard deviations(RSD) and the relative errors (RE) of unbound drug were 2.1%-5.02% and 1.4%-5.8%, respectively.

Drug Interactions↗
PubMed1999

[Albumin-drug binding study by capillary electrophoresis. II. Determination of drug enantiomeric binding constants].

A capillary electrophoresis (CE) method was applied to determine the binding constants of the basic racemic drug, verapamil (VER) to human serum albumin (HSA) under drug-HSA binding equilibrium (in phosphae buffer pH 7.4, ionic strength = 0.17). In coated capillary, the unbound basic drug eluted as two zonal plateau peaks due to enantiomers separated by chiral selector (45 mmol/L trimethyl-beta-cyclodextrin dissolved in pH 2.5 phosphate buffer) at 15 kV, and their concentrations can be determined from the peak heights. To avoid disturbing the VER-HSA equilibrium, the pH 7.4 solution was used as the inlet vial buffer, and a plug(about 3 cm long) of this buffer was introduced to the capillary before injection of analyte. The binding constants were obtained from linear regression plots. The unbound concentration of S-VER was 1.67 times higher than that of the antipode for the solution 300 mumol/L (+/-) VER-500 mumol/L HSA, while 1.13 for 100 mumol/L (+/-) VER-100 mumol/L HSA. The study confidently provides the binding constants of VER enantiomers to HSA, which are KR = 2.7 x 10(3) (+/- 4.4 x 10(2)) and Ks = 8.5 x 10(3) (+/- 1.0 x 10(2)).

Binding, Competitive↗
PubMed1999

[Chiral resolution by capillary electrophoresis].

The application and development in the field of chiral resolution by capillary electrophoresis are reviewed according to recent references, including different operating models and different chiral selectors. The study on mechanism of chiral resolution is summarized as well. It appears that capillary electrophoresis is one of the most effective, fast and simple methods in chiral resolution.

Cyclodextrins↗
PubMed1998

Cloning and characterization of cDNAs encoding a candidate glycogen storage disease type 1b protein in rodents.

Glycogen storage disease type 1 (GSD-1) is a group of genetic disorders caused by a deficiency in the activity of the enzyme glucose-6-phosphatase. (G6Pase). GSD-1a and GSD-1b, the two major subgroups, have been confirmed at the molecular genetic level. The gene responsible for GSD-1b maps to human chromosome 11q23 and a candidate human GSD-1b cDNA that encodes a microsomal transmembrane protein has been identified. In this study, we show that this cDNA maps to chromosome 11q23; thus it is a strong candidate for GSD-1b. Furthermore, we isolated and characterized candidate murine and rat GSD-1b cDNAs. Both encode transmembrane proteins sharing 93-95% sequence homology to the human GSD-1b protein. The expression profiles of murine GSD-1b and G6Pase differ both in the liver and in the kidney; the GSD-1b transcript appears before the G6Pase mRNA during development. In addition to G6Pase deficiency, GSD-1b patients suffer neutropenia, neutrophil dysfunction, and recurrent bacterial infections. Interestingly, although the G6Pase mRNA is expressed primarily in the liver, kidney, and intestine, the GSD-1b mRNA is expressed in numerous tissues, including human neutrophils/monocytes.

Adult↗
PubMed1998

Intracellular retention of duck hepatitis B virus large surface protein is independent of preS topology.

The mechanism of intracellular retention for the large surface protein (L) of duck hepatitis B virus (DHBV) was analyzed by examination of the transmembrane topologies and secretory properties of a collection of DHBV L mutants and compared with that of human hepatitis B virus (HBV) L. Our results demonstrate that, in contrast to its HBV counterpart, intracellular retention of DHBV L does not depend on the cytosolic disposition of its preS domain. L mutants with either cytosolic or lumenal preS were mostly retained in the absence of the small surface protein (S), whereas coexpression with S resulted in efficient secretion of both topological forms. Coexpression of the wild-type DHBV L with S resulted in efficient incorporation of L into secreted S + L particles, whereas HBV L was partially excluded from secreted particles under the same conditions. We propose that HBV provides L retention even in the presence of an excess of S, by exclusion of molecules with cytosolic preS domains from secreted particles at the stage of their assembly. DHBV lacks such a retention mechanism due to the absence of topological selection in particulate assembly.

Animals↗
PubMed1998

Separation of enantiomers of drugs by capillary electrophoresis. V. Hydroxypropyl-alpha-cyclodextrin as chiral solvating agent.

In an extended chiral drug screening program, enantioseparation of 86 racemic drugs was tested with hydroxypropyl-alpha-cyclodextrin as chiral solvating agent (CSA). A total of 34 drugs out of 86 could be resolved in this straightforward approach. The number of experiments performed under identical conditions allows a correlation of the separation factors alpha(m) with the interaction strengths Rm. As shown for a subset of 23 drugs, the concentration of the CSA is a crucial parameter for further optimization.

2-Hydroxypropyl-beta-cyclodextrin↗