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Biomedical subjects

J Tu

Publications and source records attributed to J Tu.

At least 19 recordsLinked to original sources
PubMed2005

Alginate microparticles prepared by spray-coagulation method: preparation, drug loading and release characterization.

A spray-coagulation method was developed for the preparation of large scale of porous alginate microparticles. The effect of three variables on porosity was evaluated: (1) alginate solution concentration (2) the concentration of CaCl2 in the coagulation medium and (3) the ratio of guluronic acid to manuronic acid of the alginate. Methylene blue (MB), a highly water-soluble compound and a practically water-insoluble compound, 4-phenylazoaniline (PAA) were used as the model drugs to study drug loading and release characteristics from alginate microparticles. The release of the model compounds from the microparticles was found to depend upon the release medium. Incomplete in vitro release of both model drugs in deionized (DI) water was observed. The release of MB in simulated gastrointestinal fluid (0.1N HCl) was fast and complete, while the release of PAA was slow in 0.1N HCl and fast in phosphate buffer solution (pH 6.8). Interactions between the model drugs and alginate microparticles were identified from scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) analysis. The results indicated that (1) porous alginate microparticles can be produced by the spray-coagulation method; (2) drugs can be loaded by the adsorption method; (3) and the obtained microparticles may be used for delaying the release of drugs of low water solubility in acidic conditions.

Adsorption↗
PubMed2002

Pyramiding transgenes for multiple resistance in rice against bacterial blight, yellow stem borer and sheath blight.

Here we describe the development of transgene-pyramided stable elite rice lines resistant to disease and insect pests by conventional crossing of two transgenic parental lines transformed independently with different genes. The Xa21 gene (resistance to bacterial blight), the Bt fusion gene (for insect resistance) and the chitinase gene (for tolerance of sheath blight) were combined in a single rice line by reciprocal crossing of two transgenic homozygous IR72 lines. F4 plant lines carrying all the genes of interest stably were identified using molecular methods. The identified lines, when exposed to infection caused by Xanthomonas oryzae pv oryzae, showed resistance to bacterial blight. Neonate larval mortality rates of yellow stem borer ( Scirpophaga incertulas) in an insect bioassay of the same identified lines were 100%. The identified line pyramided with different genes to protect against yield loss showed high tolerance of sheath blight disease caused by Rhizoctonia solani.

Animals↗
PubMed2001

Enhanced resistance to sheath blight by constitutive expression of infection-related rice chitinase in transgenic elite indica rice cultivars.

Genetic transformation has been attempted for management of rice sheath blight disease, caused by Rhizoctonia solani. We introduced a PR-3 rice chitinase gene (RC7), isolated from R. solani-infected rice plants, into indica rice cultivars IR72, IR64, IR68899B, MH63, and Chinsurah Boro II by the biolistic and PEG-mediated transformation system. Inheritance was studied up to the T(2) generation by Southern blot analysis. Western blot analysis of transgenic plants with polyclonal antibody revealed the presence of chitinase protein with a molecular weight of 35 kDa that reacts with chitinase antibody. The transformants synthesized different levels of chitinase proteins constitutively and progeny from the plants containing the chitinase gene showed different levels of enhanced resistance when challenged with the sheath blight pathogen R. solani.

Journal Article↗
PubMed2001

1,2,5-Thiadiazolidin-3-one 1,1 dioxide: a powerful scaffold for probing the S' subsites of (chymo)trypsin-like serine proteases.

The 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold (I) embodies a motif that allows it to dock to the active site of (chymo)trypsin-like proteases in a predictable and substrate-like fashion. Consequently, inhibitors derived from this heterocyclic scaffold interact with both the S and S' subsites of an enzyme. Exploitation of binding interactions with both the S and S' subsites of a target enzyme may lead to compounds with greatly enhanced enzyme selectivity and inhibitory potency. This preliminary report describes the use of a series of compounds having the heterocyclic scaffold linked to various amino acids to probe the S' subsites of human leukocyte elastase (HLE), proteinase 3 (PR 3), and cathepsin G (Cat G). For comparative purposes, a series of compounds derived from a related scaffold, isothiazolidin-3-one 1,1 dioxide (II), was also generated. Several of the compounds were found to be highly potent and selective time-dependent inhibitors of HLE, PR 3, and Cat G.

Cathepsin G↗
PubMed2001

Structural and functional characterization of the lexA gene of Xanthomonas campestris pathovar citri.

The role of the LexA protein and, specifically, its effect on recA expression were analyzed in Xanthomonas campestris pathovar citri (X.c. pv. citri). Overexpression of LexA from X.c. pv. citri, in the plant pathogen, as well as in Escherichia coli, results in increased sensitivity to the DNA-damaging agents mitomycin C and ultraviolet radiation, indicating that the recombinant X.c. pv. citri LexA protein is functional in a different bacterial species. Immunoblot analysis revealed that the overexpressed LexA protein functioned as a repressor of recA expression in X.c. pv. citri, and that the mitomycin C-induced increase in the abundance of RecA was accompanied by specific proteolysis of LexA that required RecA. Although the LexA protein from X.c. pv. citri also blocked the expression of recA in E. coli, the E. coli RecA protein was not able to support the autocatalytic cleavage of LexA from the plant pathogen. The transcription start site of the X.c. pv. citri lexA gene was identified, and the region upstream of this gene was shown to confer responsiveness to mitomycin C on a luciferase reporter gene construct. Electrophoretic mobility-shift assays demonstrated that X.c. pv. citri LexA interacts with the promoter region of X.c. pv. citri lexA, as well as with those of the recA genes of X.c. pv. citri and E. coli. These results indicate that LexA functions as a repressor of gene expression in X.c. pv. citri just as it does in E. coli.

Bacterial Proteins↗
PubMed2001

Inhibition of serine proteases by functionalized sulfonamides coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold.

A challenge associated with drug design is the development of selective inhibitors of proteases (serine or cysteine) that exhibit the same primary substrate specificity, that is, show a preference for the same P(1) residue. While these proteases have similar active sites, nevertheless there are subtle differences in their S and S' subsites which can be exploited. We describe herein for the first time the use of functionalized sulfonamides as a design and diversity element which, when coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold yields potent, time-dependent inhibitors of the serine proteases human leukocyte elastase (HLE), proteinase 3 (PR 3) and cathepsin G(Cat G). Our preliminary findings suggest that (a) appending to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold recognition and diversity elements that interact with both the S and S' subsites of a target protease may result in optimal enzyme selectivity and potency and, (b) functionalized sulfonamides constitute a powerful design and diversity element with low intrinsic chemical reactivity and potentially wide applicability.

Cathepsin G↗
PubMed2001

Congenital abdominal aortic aneurysm causing renovascular hypertension, cardiomyopathy, and death in a 19-day-old neonate.

A full-term baby girl who was sent home day of life 2 was admitted to the hospital on day of life 7 for respiratory distress and poor feeding. The child was found to be hypertensive and in heart failure. Further workup led to the diagnosis of a suprarenal abdominal aortic aneurysm, but the infant had deteriorated clinically with heart failure, modest renal failure, renovascular hypertension, and no operative cure. The child died on day of life 20. Early diagnosis and prompt surgical resection are essential to managing this rare and lethal condition.

Aortic Aneurysm, Abdominal↗
PubMed2001

Formulation and pharmacokinetic studies of acyclovir controlled-release capsules.

Acyclovir controlled-release capsules (CRCs) were prepared by a three-step process: (1) melt granulation of acclovir; (2) coating of granules with ethyl-cellulose, (3) incorporation of coated granules into hard gelatin capsules. In vitro release experiments showed that the main factors affecting the release rate were the mean particle size of the actylovir raw material and the amount of coating material applied. Release of acyclovir from the capsules was in accordance with the Higuchi equation. Pharmacokinetic studies in dogs after oral administration of acyclovir controlled-release capsules showed that the formulation was successful in providing slow release of aciclovir and was superior to a commercially available controlled-release formulation.

Acyclovir↗
PubMed2001

[Recombinant Salmonella typhimurium anticaries vaccine. II. Construction and confirmation of expressing plasmid carrying a region of S. mutans pac gene].

OBJECTIVE: The objective of this study is to construct prokaryotic expressing plasmids carrying A region of S. mutans pac gene. METHODS: The A region of pac gene was amplified by using PCR from plasmid pPC41 containing S. mutans surface protein pac gene. The new expression plasmid was constructed by using A region of pac gene and expressing plasmids pET17-b and directed cloning technique. The recombinant plasmid was identified by agarose gel electrophoresis after it was cut by using BamHI and EcoRV. RESULTS: The expressing plasmid carrying pac gene A region was acquired. CONCLUSION: The recombinant plasmid provides useful experimental materials for further research work.

Dental Caries↗
PubMed2000

Molecular characterization of a granulocyte macrophage-colony-stimulating factor receptor alpha subunit-associated protein, GRAP.

The granulocyte macrophage-colony-stimulating factor receptor (GM-CSF-R) is a heterodimer composed of 2 subunits, alpha and beta, and ligand binding to the high-affinity receptor leads to signalling for the multiple actions of GM-CSF on target cells. In order to explore the role of the alpha subunit in signalling, we used a yeast-2-hybrid system to identify proteins interacting with the intracellular domain of the GMR-alpha. A cDNA encoding a predicted protein of 198 amino acids, designated GRAP (GM-CSF receptor alpha subunit-associated protein), was isolated in experiments using the intracellular portion of GMR-alpha as bait. The interaction between GRAP and GMR-alpha was confirmed by coimmunoprecipitation in mammalian cells. GRAP mRNA is widely expressed in normal human and mouse tissues and in neoplastic human cell lines, but it is not restricted to cells or tissues that express GM-CSF receptors. Three discrete GRAP mRNA species were detected in human tissues and cells, with estimated sizes of 3.3, 3.1, and 1.3 kb. GRAP is highly conserved throughout evolution, and homologues are found in yeast. The GRAP locus in Saccharomyces cerevisiae was disrupted, and mutant yeast cells showed an inappropriate stress response under normal culture conditions, manifested by early accumulation of glycogen during the logarithmic growth phase. GRAP is, therefore, a highly conserved and widely expressed protein that binds to the intracellular domain of GMR-alpha, and it appears to play an important role in cellular metabolism.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Utilization of the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold in the design of potent inhibitors of serine proteases: SAR studies using carboxylates.

A series of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide and isothiazolidin-3-one 1,1 dioxide scaffolds has been synthesized and the inhibitory profile of these compounds toward human leukocyte elastase (HLE), cathepsin G (Cat G) and proteinase 3 (PR 3) was then determined. Most of the compounds were found to be potent, time-dependent inhibitors of elastase, with some of the compounds exhibiting k(inact)/K1 values as high as 4,928,300 M(-1) s(-1). The inhibitory potency of carboxylate derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide platform was found to be influenced by both the pKa and the inherent structure of the leaving group. Proper selection of the primary specificity group (R(I)) was found to lead to selective inhibition of HLE over Cat G, however, those compounds that inhibited HLE also inhibited PR 3, albeit less efficiently. The predictable mode of binding of these compounds suggests that, among closely-related serine proteases, highly selective inhibitors of a particular serine protease can be fashioned by exploiting subtle differences in their S' subsites. This study has also demonstrated that the degradative action of elastase on elastin can be abrogated in the presence of inhibitor 17.

Cyclic S-Oxides↗
PubMed2000

Potent inhibition of serine proteases by heterocyclic sulfide derivatives of 1,2,5-thiadiazolidin-3-one 1,1 dioxide.

The existence of subtle differences in the Sn' subsites of closely-related (chymo)trypsin-like serine proteases, and the fact that the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold docks to the active site of (chymo)trypsin-like enzymes in a substrate-like fashion, suggested that the introduction of recognition elements that can potentially interact with the Sn' subsites of these proteases might provide an effective means for optimizing enzyme potency and selectivity. Accordingly, a series of heterocyclic sulfide derivatives based on the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold (I) was synthesized and the inhibitory activity and selectivity of these compounds toward human leukocyte elastase (HLE), proteinase 3 (PR 3) and cathepsin G (Cat G) were then determined. Compounds with P1 = isobutyl were found to be potent, time-dependent inhibitors of HLE and, to a lesser extent PR 3, while those with P1 = benzyl inactivated Cat G rapidly and irreversibly. This study has demonstrated that 1,2,5-thiadiazolidin-3-one 1,1 dioxide-based heterocyclic sulfides are effective inhibitors of (chymo)trypsin-like serine proteases.

Cathepsin G↗
PubMed2000

Field performance of transgenic elite commercial hybrid rice expressing bacillus thuringiensis delta-endotoxin.

Here we describe development of transgenic elite rice lines expressing a Bt fusion gene derived from cryIA(b) and cryIA(c) under the control of rice actinI promoter. The lines used in the study were indica CMS restorer line of Minghui 63 and its derived hybrid rice Shanyou 63. The level of Bt fusion protein CryIA(b)/CryIA(c) detected in Minghui 63 (T51-1) plants was 20 ng/mg soluble protein. The Bt Shanyou 63 was field-tested in natural and repeated heavy manual infestation of two lepidopteran insects, leaffolder and yellow stem borer. The transgenic hybrid plants showed high protection against both insect pests without reduced yield.

Actins↗
PubMed2000

[The spectroscopic study of topaz].

In this paper, the natural gem material--Topaz (colorless transparent samples and reactor irradiation induced blue color samples) was studied on the spectroscopic analysis of Fourier transformation infrared spectrum (FTIR) and FT-Raman spectrum. The structure of topaz consists of OH groups and SiO4 groups. Si-O vibration spectrum was characterized with the group theoretical analysis. OH stretching modes of vibration showed many changes among the different color samples, the reason of the changes was explained. The color origin was preliminary investigated by ultra-violet and visible absorption spectrum.

Resin Cements↗
PubMed1999

Expression and regulation of glucokinase in rat islet beta- and alpha-cells during development.

Glucokinase (GK) is the rate-limiting enzyme in the glycolytic pathway of the beta-cell and, even in the rat fetus at 22-days gestation, immediately before birth, acts as a sensor of glucose influencing the rate of glucose utilization. However, when GK first appears in islets during beta-cell development is unknown. Whether GK is expressed in fetal glucagon-producing cells is also unknown. To determine this information, fetal rat islets were examined at 16-, 18-, and 22-days gestation. GK was identified immunocytochemically in both beta- and alpha-cells at all these ages, with the number of GK immunoreactive cells positively correlated to the fetal age from 16-22 days. Western blot analysis of islet protein extracts demonstrated the presence of GK, at 52 kDa, at 16 days and thereafter. To determine whether glucose had any effect on regulation of GK biosynthesis, fetal islets were cultured in medium containing a wide range of concentrations of glucose for 7 days. The amount of GK protein was significantly decreased in low concentrations of glucose and augmented at high concentrations. In conclusion, GK was expressed in both beta- and alpha-cells in fetal rat islets during development. GK is an integral part of the function of both of these cells at all stages in the development of the fetal islet.

Aging↗