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10837710
Cyclodextrins in transdermal and rectal delivery.
Transdermal and rectal routes of drugs are very important as a useful supplement of oral routes and the direct exposing method of drugs when the systemic and local effects are required. The widespread use of parent cyclodextrins (CDs) and chemically modified CD derivatives (CD derivatives) for in-vitro and in-vivo derm...
10837709
Cyclodextrins in ophthalmic drug delivery.
Most ocular diseases are treated by topical drug application in the form of aqueous eye drop solutions. Recent studies have shown that cyclodextrins are useful additives in ophthalmic formulations for increasing the aqueous solubility, aqueous stability and bioavailability of ophthalmic drugs, and to decrease drug irri...
10837708
Cyclodextrins in nasal drug delivery.
Nasal drug delivery is an attractive approach for the systemic delivery of high potency drugs with a low oral bioavailability due to extensive gastrointestinal breakdown and high hepatic first-pass effect. For lipophilic drugs nasal delivery is possible if they can be dissolved in the dosage form. Peptide and protein d...
10837707
Cyclodextrins in targeting. Application to nanoparticles.
For some years cyclodextrins and their hydrophilic derivatives have been described in the literature as solubilizers capable of enhancing the loading capacity of liposomes and microparticles. We present here two new possibilities of using cyclodextrins in the design of colloidal carriers. The first possibility consists...
10837706
Highly soluble cyclodextrin derivatives: chemistry, properties, and trends in development.
As the first pharmaceutical products which contain highly soluble cyclodextrin (CD) derivatives (e.g. Sporanox=itraconazole/HP-beta-CD by Janssen and Clorocil=chloramphenicol/methyl-beta-CD by Oftalder) are already on the market it seems to be timely to give an overview on the technological and commercial aspects of th...
10837705
Mechanisms of drug release from cyclodextrin complexes.
This review addresses the issue of the mechanisms of drug release from cyclodextrin complexes. More specifically, it attempts to answer the question whether drug release from aqueous formulations is slow or incomplete? A critique of the literature, our own work, and various simulations suggests that drug release from c...
10205296
Fluorescence study of conformational transitions in the structure of myoglobin
Fluorescence studies of myoglobin and Mb-like structures, apomyoglobin and the complex of apo-Mb with protoporphyrin IX, reveal both the similarity between them, which is due to a common type of polypeptide chain folding, and the distinctions imposed by the influence of the prosthetic group. Close resemblance of struct...
10049864
Induction of defense responses in cucumber plants (Cucumis sativus L. ) By the biocontrol agent trichoderma harzianum
The potential of the biocontrol agent Trichoderma harzianum T-203 to trigger plant defense responses was investigated by inoculating roots of cucumber seedlings with Trichoderma in an aseptic, hydroponic system. Trichoderma-treated plants were more developed than nontreated plants throughout the experiment. Electron mi...
11674216
Site-Directed Mutagenesis of the Sterol Methyl Transferase Active Site from Saccharomyces cerevisiae Results in Formation of Novel 24-Ethyl Sterols.
Delta(24(28))-Sterols are end products of a mono C-methylation pathway catalyzed by the native Delta(24(25))- to Delta(24(28))-sterol methyl transferase (SMT) enzyme from Saccharomyces cerevisiae. Using a Tyr(81) to Phe mutant SMT enzyme of S. cerevisiae, generated by site-directed mutagenesis of a highly conserved res...
11674211
1H and (13)C NMR and Molecular Dynamics Study of Chiral Recognition of Camphor Enantiomers by alpha-Cyclodextrin.
1H and (13)C NMR spectra of the complexes of camphor enantiomers with alpha-cyclodextrin in D(2)O manifest splittings due to chiral recognition. The complexes were found to be of 1:2 guest-to-host stoichiometry. Free energies of the complex formation obtained from (1)H NMR titration data are equal to -7.95 +/- 0.09 kca...
11674209
Molecular Recognition Study on Supramolecular Systems. 20. Molecular Recognition and Enantioselectivity of Aliphatic Alcohols by L-Tryptophan-Modified beta-Cyclodextrin.
L-Tryptophan-modified beta-cyclodextrin (L-Trp-beta-CD) has been synthesized and its molecular recognition behavior investigated through fluorescence and circular dichroism spectrometry, as well as fluorescence lifetime measurement in the presence and absence of various alcohols as guest molecules. Employing the indoly...
11674201
Proton-Template Synthesis, Structure, and Characterization of a Robson-Type Macrocycle with a Totally pi-Conjugated System.
pi-Conjugated (1-4) and partially reduced (5) macrocyclic Schiff bases have been obtained by proton-template condensation of 2,6-diformyl-4-R(1)-phenol (R(1) = Me, t-Bu) with 1,2-diamino-4,5-R(2)-benzene (R(2) = H, Me). The macrocyclic ligands have been characterized by elemental analysis, by IR, (1)H NMR, and (13)C NM...
11670908
Formation of Dinuclear Copper(II) Complexes from a Macrocycle with Built-in Pyrazole Groups.
The 22-membered macrocycle, containing four endocyclic pyrazole groups and two exocyclic pyridine groups, viz. (9,22-di(pyridin-2-ylmethyl)-1,4,9,14,17,22,27,28,29,30-decaaza-5,13,18,26-tetramethyl)pentacyclo[24.2.1.1(4,7).1(11,14).1(17,20)]triacontane-5,7(28),11(29),12,18,20(30),24(27),25-octaene (MePy22Pz), has been ...
11670904
Unusual Me-O Bond Cleavage in a Metalated Crown-Ether: X-ray Molecular Structure of (5-Methoxy-4,6-dimethyl-1,3-xylylene-2-one)-15 Crown-4 Complex of Pentamethylcyclopentadienyl Iridium.
The reaction of [(C(5)Me(5))Ir(Solvent)(3)][BF(4)](2) (1) with (2,5-dimethoxy-4,6-dimethyl-1,3-xylylene)-15 crown-4 (2) affords the metalated crown-ether complex [(eta(5)-C(5)Me(5))Ir(eta(6)-C(18)H(28)O(6))][BF(4)](2) (3) in 88% yield. Complex 3 undergoes a facile Me-O bond cleavage to give the related semiquinone form...
11670864
Metal Complexes of Pyridylphenylisocyanides and Pyridylethynylphenylisocyanides as Building Blocks for Coordination Polymers and Supramolecular Assemblies.
The isocyanides 3-(4-pyridylethynyl)phenylisocyanide, 3, 4-(4-pyridylethynyl)phenylisocyanide, 6, 2,6-diisopropyl-4-(4-pyridylethynyl)phenylisocyanide, 9, and 2,6-diisopropyl-4-(4-pyridyl)phenylisocyanide, 11, were prepared. With PdI(2) and PtI(2), these isocyanides form the complexes trans-[MI(2)(CNR)(2)], 12-19 (M = ...
11670856
Solution and Solid State Structure of a Canted, Side-to-Face, Bis(porphyrin) Adduct.
The coordination chemistry of meso-pyridyl/phenyl porphyrins (PyPs) toward metallo-porphyrins with substitutionally labile axial ligands has been exploited for the self-assembling of ordered arrays of pigments. PyPs are particularly versatile bulding blocks: the peripheral N atom can be either in the 4'-position (4'PyP...
10077607
Periodical distribution of transcription factor sites in promoter regions and connection with chromatin structure.
Nucleosomes regulate transcriptional initiation when positioned in the promoter area. This may require the transcription factor (TF) sites to be correlated with the nucleosome positions and phased on the nucleosome surface. If this is the case, one would expect a periodical distribution of TF sites in the vicinity of p...
10077589
Estradiol induces the calcium-dependent translocation of endothelial nitric oxide synthase.
Although estrogen is known to stimulate nitric oxide synthesis in vascular endothelium, the molecular mechanisms responsible for this effect remain to be elucidated. Using quantitative immunofluorescence imaging approaches, we have investigated the effect of estradiol on the subcellular targeting of endothelial nitric ...
10077582
Phosphorylating DNA with DNA.
Nearly 50 individual DNAs with polynucleotide kinase-like activity were isolated from a random-sequence pool by using in vitro selection. Each self-phosphorylating deoxyribozyme makes use of one or more of the eight standard NTPs or dNTPs as a source of activated phosphate. Although most prototypic deoxyribozymes poorl...
10077580
In vitro suicide inhibition of self-splicing of a group I intron from Pneumocystis carinii by an N3' --> P5' phosphoramidate hexanucleotide.
Binding enhancement by tertiary interactions is a strategy that takes advantage of the higher order folding of functionally important RNAs to bind short nucleic acid-based compounds tightly and more specifically than possible by simple base pairing. For example, tertiary interactions enhance binding of specific hexamer...
10077568
Transcriptional activation by artificial recruitment in yeast is influenced by promoter architecture and downstream sequences.
The idea that recruitment of the transcriptional machinery to a promoter suffices for gene activation is based partly on the results of "artificial recruitment" experiments performed in vivo. Artificial recruitment can be effected by a "nonclassical" activator comprising a DNA-binding domain fused to a component of the...
10077560
Structural characteristics of supramolecular assemblies formed by guanidinium-cholesterol reagents for gene transfection.
We have recently discovered that cationic cholesterol derivatives characterized by guanidinium polar headgroups are very efficient for gene transfection in vitro and in vivo. In spite of being based on some rationale at the molecular level, the development of these new synthetic vectors was nevertheless empirical. Inde...
10075938
Self assembly of NuMA: multiarm oligomers as structural units of a nuclear lattice.
NuMA is a nuclear matrix protein in interphase and relocates to the spindle poles in mitotis. Different NuMA constructs, in which either N- or C-terminal domains were deleted, and the full-length construct were expressed in Escherichia coli, and the NuMA polypeptides were purified to homogeneity and allowed to assemble...
10075932
A trans-acting peptide activates the yeast a1 repressor by raising its DNA-binding affinity.
The cooperative binding of gene regulatory proteins to DNA is a common feature of transcriptional control in both prokaryotes and eukaryotes. It is generally viewed as a simple energy coupling, through protein-protein interactions, of two or more DNA-binding proteins. In this paper, we show that the simple view does no...
10077477
Inhibition of viral adhesion and infection by sialic-acid-conjugated dendritic polymers.
Multiple sialic acid (SA) residues conjugated to a linear polyacrylamide backbone are more effective than monomeric SA at inhibiting influenza-induced agglutination of red blood cells. However, "polymeric inhibitors" based on polyacrylamide backbones are cytotoxic. Dendritic polymers offer a nontoxic alternative to pol...
10049388
Peptidoglycan-hydrolyzing activity of the FlgJ protein, essential for flagellar rod formation in Salmonella typhimurium.
Because the rod structure of the flagellar basal body crosses the inner membrane, the periplasmic space, and the outer membrane, its formation must involve hydrolysis of the peptidoglycan layer. So far, more than 10 genes have been shown to be required for rod formation in Salmonella typhimurium. Some of them encode th...
10072328
Plasmodium falciparum: structural and functional domains of the mature-parasite-infected erythrocyte surface antigen.
The mature parasite-infected erythrocyte surface antigen (MESA) is a protein exported to the membrane skeleton of the infected red cell, where it forms a strong noncovalent interaction with the host red cell protein, protein 4.1. The complete gene structure of MESA from the Ugandan isolate Palo Alto is described. Compa...
10071835
The effect of 2-hydroxypropyl-beta-cyclodextrin on in vitro drug release of steroids from suppository bases.
The effects of 2-hydroxypropyl-beta-cyclodextrin (HPCD) on drug solubility and drug release from suppository bases were studied for dexamethasone (DX), dexamethasone acetate (DXA), hydrocortisone (HC), hydrocortisone acetate (HCA), and prednisolone acetate (PNA). It was found that HPCD significantly increased the aqueo...
10071820
Effects of the host cavity size and the preparation method on the physicochemical properties of ibuproxam-cyclodextrin systems.
The effect of cyclodextrin (Cd) complexation on ibuproxam (IBUX) dissolution properties was studied by evaluating both the influence of Cd cavity size and the preparation method used for obtaining solid inclusion complexes. Binary systems of IBUX with natural Cds, prepared using different techniques (kneading, sealed-h...
10068518
Ischemia-reperfusion protects the rat small intestine against subsequent injury.
<h4>Background</h4>It has been suggested that multiple sublethal insults are commonly associated with the development of multiple organ failure (MOF). The gut is considered to be pivotal in the pathogenesis of MOF. This study investigated the effects of repeated ischemia-reperfusion of the rat small intestine.<h4>Metho...
10069046
Do charge-remote fragmentations occur under matrix-assisted laser desorption ionization post-source decompositions and matrix-assisted laser desorption ionization collisionally activated decompositions?
The precursor ions of tetraphenylporphyrins that are substituted with fatty acids can be introduced into the gas phase by matrix-assisted laser desorption ionization (MALDI) and undergo post-source and collisionally activated decompositions (CAD) in a time-of-flight mass spectrometer. The goal of the research is to obt...
10066836
Surface proteins of gram-positive bacteria and mechanisms of their targeting to the cell wall envelope.
The cell wall envelope of gram-positive bacteria is a macromolecular, exoskeletal organelle that is assembled and turned over at designated sites. The cell wall also functions as a surface organelle that allows gram-positive pathogens to interact with their environment, in particular the tissues of the infected host. A...
10064890
Differential expression of inflammatory mediators in rat microglia cultured from different brain regions.
Microglial cells show a rather uniform distribution of cell numbers throughout the brain with only minor prevalences in some brain regions. Their in situ morphologies, however, may vary markedly from elongated forms observed in apposition with neuronal fibers to spherical cell bodies with sometimes extremely elaborated...
10053216
Characterization of itraconazole/2-hydroxypropyl-beta-cyclodextrin inclusion complex in aqueous propylene glycol solution.
The interaction of itraconazole, a triazole antifungal agent, with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) in water and 10% v/v propylene glycol/water solution at pH 2.0 was investigated by the solubility method and ultraviolet and 1H-nuclear magnetic resonance (NMR) spectroscopies. The solubility of itraconazo...
10053215
Formulation of triamcinolone acetonide pellets suitable for coating and colon targeting.
Spherical pellets containing 5% of triamcinolone acetonide (TA) were formed by extrusion/spheronization following formulation with microcrystalline cellulose (MCC) and/or a hydrophilic excipient (lactose, sodium carboxymethylcellulose or beta-cyclodextrin, beta-CD). Their suitability for coating, with a view to colonic...
10053208
Influence of the preparation method on the physicochemical properties of ketoprofen-cyclodextrin binary systems.
Binary systems of ketoprofen with native crystalline beta-cyclodextrin and amorphous statistically substituted methyl-beta-cyclodextrin were investigated for both solid phase characterization (Differential Scanning Calorimetry, powder X-ray diffraction, Infrared Spectroscopy, Scanning Electron Microscopy) and dissoluti...
10053203
Improvement of the in vitro dissolution of praziquantel by complexation with alpha-, beta- and gamma-cyclodextrins.
Although praziquantel (PZQ) is the primary drug of choice in the treatment of schistosomiasis, its poor solubility has restricted its delivery via the oral route. In spite of its poor solubility, PZQ is well absorbed across the gastrointestinal tract, but large doses are required to achieve adequate concentrations at t...
10053187
Stabilization of proteins against methylene chloride/water interface-induced denaturation and aggregation.
The purpose of this study was to stabilize proteins during the commonly used microencapsulation process of methylene chloride/water emulsification. The model proteins used in this study included bovine serum albumin (BSA), S-carboxymethylated BSA (CM-BSA), reduced-S-carboxymethylated BSA (RCM-BSA), ovalbumin, and lysoz...
10064607
P1 ParA interacts with the P1 partition complex at parS and an ATP-ADP switch controls ParA activities.
The partition system of P1 plasmids is composed of two proteins, ParA and ParB, and a cis-acting site parS. parS is wrapped around ParB and Escherichia coli IHF protein in a higher order nucleoprotein complex called the partition complex. ParA is an ATPase that autoregulates the expression of the par operon and has an ...
10064606
Mutants of Tn3 resolvase which do not require accessory binding sites for recombination activity.
Tn3 resolvase promotes site-specific recombination between two res sites, each of which has three resolvase dimer-binding sites. Catalysis of DNA-strand cleavage and rejoining occurs at binding site I, but binding sites II and III are required for recombination. We used an in vivo screen to detect resolvase mutants tha...
10064587
A region of the Yersinia pseudotuberculosis invasin protein enhances integrin-mediated uptake into mammalian cells and promotes self-association.
Invasin allows efficient entry into mammalian cells by Yersinia pseudotuberculosis. It has been shown that the C-terminal 192 amino acids of invasin are essential for binding of beta1 integrin receptors and subsequent uptake. By analyzing the internalization of latex beads coated with invasin derivatives, an additional...
10064583
The EH and SH3 domain Ese proteins regulate endocytosis by linking to dynamin and Eps15.
Clathrin-mediated endocytosis is a multistep process which requires interaction between a number of conserved proteins. We have cloned two mammalian genes which code for a number of endocytic adaptor proteins. Two of these proteins, termed Ese1 and Ese2, contain two N-terminal EH domains, a central coiled-coil domain a...
10064580
Head-to-tail dimers and interdomain flexibility revealed by the crystal structure of HIV-1 capsid protein (p24) complexed with a monoclonal antibody Fab.
The crystal structure of an intact molecule of HIV-1 capsid protein (p24) in complex with a monoclonal antibody fragment recognizing an epitope on the C-terminal domain has been determined at 3 A resolution. The helical N- and C-terminal domains of p24 are linked by an extended peptide forming a flexibly linked dumb-be...
10051566
Small antibody-like proteins with prescribed ligand specificities derived from the lipocalin fold.
We demonstrate that the ligand pocket of a lipocalin from Pieris brassicae, the bilin-binding protein (BBP), can be reshaped by combinatorial protein design such that it recognizes fluorescein, an established immunological hapten. For this purpose 16 residues at the center of the binding site, which is formed by four l...
10051560
Structure of a cytochrome P450-redox partner electron-transfer complex.
The crystal structure of the complex between the heme- and FMN-binding domains of bacterial cytochrome P450BM-3, a prototype for the complex between eukaryotic microsomal P450s and P450 reductase, has been determined at 2.03 A resolution. The flavodoxin-like flavin domain is positioned at the proximal face of the heme ...
10052991
Interaction between surface active drug (FK906:rennin inhibitor) and cyclodextrins in aqueous solution.
The aggregation behavior of FK906, which is a peptide like hypertensive agent, in aqueous solution was studied by static light scattering, 1H-nuclear magnetic resonance (NMR), and surface tension. These experiments showed a clear critical micelle concentration (cmc) at around 6.3 x 10(-3) to 1.3 x 10(-2) M of FK906 aqu...
10052987
Pharmacokinetic analysis of 6-monoamino-beta-cyclodextrin after intravenous or oral administration to rats using a specific enzyme immunoassay.
We have developed a highly sensitive enzyme immunoassay for 6-monoamino-beta-CD (mono(6-amino-6-deoxy)cyclomaltoheptaose) and its parent compound (beta-CD) with a detection limit in the 100 pg/mL range. The polyclonal antibodies obtained are highly specific for the beta-cyclodextrin core and do not recognize other cycl...
10051522
Occupancy of the chromophore binding site of opsin activates visual transduction in rod photoreceptors.
The retinal analogue beta-ionone was used to investigate possible physiological effects of the noncovalent interaction between rod opsin and its chromophore 11-cis retinal. Isolated salamander rod photoreceptors were exposed to bright light that bleached a significant fraction of their pigment, were allowed to recover ...
10052950
Resonance Raman investigation of nickel microperoxidase-11.
Resonance Raman and UV-visible absorption spectra show that nickel(II) microperoxidase-11 (NiMP-11) is four-coordinate in aqueous solution in the pH range from 1.0 to 13.0. In aqueous solutions of NiMP-11 in the absence of cetyltrimethylammonium bromide (CTAB), NiMP-11 is aggregated. In CTAB micellar solutions, where a...
10049873
Isolation from estuarine sediments of a Desulfovibrio strain which can grow on lactate coupled to the reductive dehalogenation of 2,4, 6-tribromophenol.
Strain TBP-1, an anaerobic bacterium capable of reductively dehalogenating 2,4,6-tribromophenol to phenol, was isolated from estuarine sediments of the Arthur Kill in the New York/New Jersey harbor. It is a gram-negative, motile, vibrio-shaped, obligate anaerobe which grows on lactate, pyruvate, hydrogen, and fumarate ...
10049844
Role of the Trichoderma harzianum endochitinase gene, ech42, in mycoparasitism.
The role of the Trichoderma harzianum endochitinase (Ech42) in mycoparasitism was studied by genetically manipulating the gene that encodes Ech42, ech42. We constructed several transgenic T. harzianum strains carrying multiple copies of ech42 and the corresponding gene disruptants. The level of extracellular endochitin...
10049841
Thermus aquaticus ATCC 33923 amylomaltase gene cloning and expression and enzyme characterization: production of cycloamylose.
The amylomaltase gene of the thermophilic bacterium Thermus aquaticus ATCC 33923 was cloned and sequenced. The open reading frame of this gene consisted of 1,503 nucleotides and encoded a polypeptide that was 500 amino acids long and had a calculated molecular mass of 57,221 Da. The deduced amino acid sequence of the a...
10047476
Folding and self-assembly of the domains of betaB2-crystallin from rat eye lens.
betaB2-Crystallin from vertebrate eye lens forms domain-swapped dimers, with subunits consisting of two all-beta domains connected by an eight-residue extended linker peptide. Topologically, the two domains show great similarity; however, they differ widely in their stability. As shown by urea-induced equilibrium unfol...
10049344
Polarization-modulated FTIR spectroscopy of lipid/gramicidin monolayers at the air/water interface.
Monolayers of gramicidin A, pure and in mixtures with dimyristoylphosphatidylcholine (DMPC), were studied in situ at the air/H2O and air/D2O interfaces by polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). Simulations of the entire set of amide I absorption modes were also performed, using c...
10049341
Model-independent analysis of the orientation of fluorescent probes with restricted mobility in muscle fibers.
The orientation of proteins in ordered biological samples can be investigated using steady-state polarized fluorescence from probes conjugated to the protein. A general limitation of this approach is that the probes typically exhibit rapid orientational motion ("wobble") with respect to the protein backbone. Here we pr...
10037819
Oligonucleotide-europium complex conjugate designed to cleave the 5' cap structure of the ICAM-1 transcript potentiates antisense activity in cells.
The 5' cap structure of mRNA is a N7 methylated guanosine residue that is linked by a 5'-5' triphosphate linkage to the 5'-terminus of cellular and viral RNAs synthesized by RNA polymerase II. This unique structure facilitates several processes of mRNA metabolism, including splicing, nucleocytoplasmic transport,initiat...
10037806
hnRNP C and polypyrimidine tract-binding protein specifically interact with the pyrimidine-rich region within the 3'NTR of the HCV RNA genome.
Like other members of the Flaviviridae family, the 3' non-translated region (NTR) of the hepatitis C virus (HCV) is believed to function in the initiation and regulation of viral RNA replication by interacting with components of the viral replicase complex. To inves-tigate the possibility that host components may also ...
10024532
Variable domain-linked oligosaccharides of a human monoclonal IgG: structure and influence on antigen binding.
The variable-domain-attached oligosaccharide side chains of a human IgG produced by a human-human-mouse heterohybridoma were analysed. In addition to the conserved N-glycosylation site at Asn-297, an N-glycosylation consensus sequence (Asn-Asn-Ser) is located at position 75 in the variable region of its heavy chain. Th...
10024526
Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor.
A novel and potent azetidinone inhibitor of the lipoprotein-associated phospholipase A2 (Lp-PLA2), i.e. platelet-activating factor acetylhydrolase, is described for the first time. This inhibitor, SB-222657 (Ki=40+/-3 nM, kobs/[I]=6. 6x10(5) M-1.s-1), is inactive against paraoxonase, is a poor inhibitor of lecithin:cho...
10024513
Comparison of the fibrin-binding activities in the N- and C-termini of fibronectin.
Fibronectin (Fn) binds to fibrin in clots by covalent and non-covalent interactions. The N- and C-termini of Fn each contain one non-covalent fibrin-binding site, which are composed of type 1 (F1) structural repeats. We have previously localized the N-terminal site to the fourth and fifth F1 repeats (4F1.5F1). In the c...
10068415
Prostanoids for chronic critical leg ischemia. A randomized, controlled, open-label trial with prostaglandin E1. The ICAI Study Group. Ischemia Cronica degli Arti Inferiori.
<h4>Background</h4>No effective pharmacologic intervention is available for critical leg ischemia, a severe clinical condition associated with high morbidity and mortality.<h4>Objective</h4>To assess the safety and efficacy of prostaglandin E1 in improving the prognosis and quality of life in patients with critical leg...
10024602
Pseudomonas aeruginosa exoenzyme S is a biglutamic acid ADP-ribosyltransferase.
Kinetic analysis of two mutations within Pseudomonas aeruginosa exoenzyme S (ExoS) showed that a E379D mutation inhibited expression of ADP-ribosyltransferase activity but had little effect on the expression of NAD glycohydrolase activity while a E381D mutation inhibited expression of both activities. These data identi...
10024592
Responses of human intestinal microvascular endothelial cells to Shiga toxins 1 and 2 and pathogenesis of hemorrhagic colitis.
Endothelial damage is characteristic of infection with Shiga toxin (Stx)-producing Escherichia coli (STEC). Because Stx-mediated endothelial cell damage at the site of infection may lead to the characteristic hemorrhagic colitis of STEC infection, we compared the effects of Stx1 and Stx2 on primary and transformed huma...
10021487
Release of testosterone from an osmotic pump tablet utilizing (SBE)7m-beta-cyclodextrin as both a solubilizing and an osmotic pump agent.
A controlled porosity osmotic pump system for poorly water soluble drugs has been developed using sulfobutyl ether-beta-cyclodextrin sodium salt, (SBE)7m-beta-CD, which can act as both a solubilizing and an osmotic agent. The release of testosterone, a poorly water soluble drug (0.039 mg/ml at 37 degrees C), was evalua...
10022893
A novel H2A/H4 nucleosomal histone acetyltransferase in Tetrahymena thermophila.
Recently, we reported the identification of a 55-kDa polypeptide (p55) from Tetrahymena macronuclei as a catalytic subunit of a transcription-associated histone acetyltransferase (HAT A). Extensive homology between p55 and Gcn5p, a component of the SAGA and ADA transcriptional coactivator complexes in budding yeast, su...
9986837
Usefulness of PCR and antigen latex agglutination test with samples obtained by transthoracic needle aspiration for diagnosis of pneumococcal pneumonia.
In a large number of cases, the etiology of community-acquired pneumonia (CAP) is not established. Some cases are probably caused by Streptococcus pneumoniae. Transthoracic needle aspiration (TNA) culture has a limited sensitivity which might be improved by antigen detection or gene amplification techniques. We evaluat...
9971909
Studies on the interaction of diflunisal ion with cyclodextrins using ion-selective electrode potentiometry.
The interaction of diflunisal ion (DF) with beta-cyclodextrin (betaCD), gamma-cyclodextrin (gammaCD), and hydroxypropyl-beta-cyclodextrin (HPbetaCD) was studied in phosphate buffer, pH 7.4, at 5-37 degrees C and various CD concentrations using a home-made diflunisal ion-selective electrode. Typical direct binding plots...
9971810
In vitro assembly properties of human immunodeficiency virus type 1 Gag protein lacking the p6 domain.
Human immunodeficiency virus type 1 (HIV-1) normally assembles into particles of 100 to 120 nm in diameter by budding through the plasma membrane of the cell. The Gag polyprotein is the only viral protein that is required for the formation of these particles. We have used an in vitro assembly system to examine the asse...
9971805
Modulation of nuclear localization of the influenza virus nucleoprotein through interaction with actin filaments.
The influenza virus genome is transcribed in the nuclei of infected cells but assembled into progeny virions in the cytoplasm. This is reflected in the cellular distribution of the virus nucleoprotein (NP), a protein which encapsidates genomic RNA to form ribonucleoprotein structures. At early times postinfection NP is...
9971781
ATP depletion blocks herpes simplex virus DNA packaging and capsid maturation.
During herpes simplex virus (HSV) assembly, immature procapsids must expel their internal scaffold proteins, transform their outer shell to form mature polyhedrons, and become packaged with the viral double-stranded (ds) DNA genome. A large number of virally encoded proteins are required for successful completion of th...
9971769
Human immunodeficiency virus type 1 protease triggers a myristoyl switch that modulates membrane binding of Pr55(gag) and p17MA.
The human immunodeficiency virus type 1 (HIV-1) Pr55(gag) gene product directs the assembly of virions at the inner surface of the cell plasma membrane. The specificity of plasma membrane binding by Pr55(gag) is conferred by a combination of an N-terminal myristoyl moiety and a basic residue-rich domain. Although the m...
12549165
[Separation of levonorgestrel, progesterone and testosterone by micellar electrokinetic capillary chromatography].
Separation of levonorgestrel, progesterone and testosterone was achieved by using micellar electrokinetic capillary chromatography (MECC). A column of 53 cm (to the detector) x 50 microns i.d. uncoated fused-silica capillary (totally 68 cm in length) and an ultra-violet detector with fixed wavelength at 254 nm were use...
12549156
[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...
12549153
[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 pe...
12549152
[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 i...
12205918
[The synthesis of multifunctional groups and multibranched compounds: IX. Synthesis of several branched building block].
The branched building plays a pivotal part in the study of Dendrimers. In order to synthesized Dendrimers more effectively, we designed and synthesized four new branched building blocks via 2-4 steps starting from diethyl malonate and pentaerythritol. Their structures were confirmed by IR and 1HNMR etc. They compare fa...
11233929
Effects of ultrasound on the formation of alpha-benzoylbenzyl cyanide from benzyl cyanide and alkylphenyl ketone from alpha-alkylbenzyl cyanide by potassium superoxide in the presence of crown ether.
Ultrasound accelerates the formation of alpha-benzoylbenzyl cyanide and benzoic acid in the reaction of benzyl cyanide with potassium superoxide in the presence of 18-crown-6. Similarly, 4-methylbenzyl cyanide, 4-methoxybenzyl cyanide and 4-chlorobenzyl cyanide gave the corresponding alpha-(4-methylbenzoyl)-4-methylben...
10704124
Mexiletine-sensitive membrane electrode for medical application.
Response characteristics of mexiletine-sensitive membrane electrodes based on crown ether and ion-exchanger were examined in a physiological saline in order to find an electrode suitable for determining concentrations of this drug under physiological conditions. Among various crown ethers screened, 4',4"(5")-di-tert-bu...
10704119
Modelling of conditions for the enantiomeric separation of beta2-adrenergic sympathicomimetics by capillary electrophoresis using cyclodextrins as chiral selectors in a polyethylene glycol gel.
A two-factor central composite design was used to determine a mathematical model for prediction of the optimal conditions for the separation of the enantiomers of some widely used beta2-sympathicomimetic drugs (beta2-agonists) by capillary electrophoresis using cyclodextrins (CD) as a chiral selector in a polyethylene ...
10704104
Characterization of the complexation of diflunisal with hydroxypropyl-beta-cyclodextrin.
The equilibrium dialysis method was applied to the determination of drug cyclodextrin stability constants using diflunisal and 2-hydroxypropyl-beta-cyclodextrin (HPBCD) as a model system. Analysis of the data showed the existence of a linear Scatchard plot, indicative of the formation of a 1:1 diflunisal:HPBCD complex....
10641162
Biodegradable dental implants of ciprofloxacin beta-cyclodextrin inclusion complex in the treatment of periodontitis.
Dental implants of ciprofloxacin beta-cyclodextrin inclusion complex were formulated using poly (epsilon-caprolactone), a biodegradable polymer and evaluated. Clinical evaluation was carried out in ten patients with acute peridontitis. Various clinical parameters, viz. gingival index, plaque score, attachment gain, red...
10398405
Targetting of the N-terminal domain of the human papillomavirus type 16 E6 oncoprotein with monomeric ScFvs blocks the E6-mediated degradation of cellular p53.
The E6 protein of cancer-associated human papillomavirus type 16 (HPV16) binds to cellular p53 and promotes its degradation through the ubiquitin pathway. In an attempt to identify the regions of E6 that could be targetted for functional inhibition, we generated monoclonal antibodies to the HPV16 E6 oncoprotein (16E6) ...
10398404
Unique single-domain antigen binding fragments derived from naturally occurring camel heavy-chain antibodies.
The humoral immune response of camels, dromedaries and llamas includes functional antibodies formed by two heavy chains and no light chains. The amino acid sequence of the variable domain of the naturally occurring heavy-chain antibodies reveals the necessary adaptations to compensate for the absence of the light chain...
10398403
Sequence-specific interactions of minor groove binders with restriction fragments of cDNAs for H tau 40 protein and MAP kinase 2. A qualitative and quantitative footprinting study.
A series of DNA minor groove binders comprising netropsin, distamycin, the bisquaternary ammonium heterocycles SN 6999 and SN 6570, cis-diammine platinum(II)-bridged bis-netropsin, cis-diammine platinum(II)-bridged bis-distamycin and bis-glycine-linked bis-distamycin were investigated for sequence-specific interactions...
10398402
Processing of PDGF gene products determines interactions with glycosaminoglycans.
The platelet derived growth factor (PDGF), a mitogen for mesenchymal cells, may be bound to and inhibited by heparin and other glycosaminoglycans. PDGF is a homo- or heterodimer of A- and B-chains. They occur as short (A109 and B110) and long (A125 and B160) isoforms. The latter contain basic carboxyl-terminal extensio...
10398401
Fine mapping of the antigen-antibody interaction of scFv215, a recombinant antibody inhibiting RNA polymerase II from Drosophila melanogaster.
A bacterially expressed single chain antibody (scFv215) directed against the largest subunit of drosophila RNA polymerase II was analysed. Structure and function of the antigen binding site in scFv215 were probed by chain shuffling and by site-specific mutagenesis. The entire variable region of either the heavy or ligh...
10398400
Biochemical purification and partial characterization of a murine macrophage surface receptor possessing specificity for small aromatic moieties including fluorescein.
Binding properties and requirements for internalization of hapten-protein antigens, such as fluorescein-polyderivatized bovine serum albumin (FITC-BSA) and poly-D-lysine (FITC-PDL), by murine macrophage was consistent with surface receptor recognition of fluorescyl moieties (Cherukuri et al., Mol. Immunol. 34, 21-32, 1...
10398399
Advances in surface plasmon resonance biomolecular interaction analysis mass spectrometry (BIA/MS).
Ongoing, worldwide efforts in genomic and protein sequencing, and the ability to readily access corresponding sequence databases, have emphatically driven the development of high-performance bioanalytical instrumentation capable of characterizing proteins and protein-ligand interactions with great accuracy, speed and s...
10342773
Designing recombinant spider silk proteins to control assembly.
The consensus repeat sequence found in the dragline silk from the spider, Nephila clavipes, was redesigned to incorporate a redox trigger flanking the beta-sheet forming polyalanine sequences. The methionine redox trigger, in the oxidized state, was incorporated to prevent the formation of the beta sheets, while in the...
10342768
The effect of post-spin drawing on spider silk microstructure: a birefringence model.
Measurements of optical birefringence have been used to characterise the effect of mechanical history on supramolecular structure in major ampullate silk from Nephila clavipes (golden orb weaver) spiders. Birefringence modelling is demonstrated to be a powerful technique for obtaining quantitative information on supram...
10342767
Spider (Araneus diadematus) cocoon silk: a case of non-periodic lattice crystals with a twist?
Transmission electron microscopy was used to investigate the supramolecular structure of Araneus diadematus (garden spider) cocoon silk. Electron diffraction patterns contain features which are consistent with the presence of non-periodic lattice crystals, i.e. highly frustrated crystalline regions as identified previo...
10336300
Structural view of cadherin-mediated cell-cell adhesion.
Following the multiplication of biochemical, biophysical and structural studies describing cadherin molecules and their interactions, several ideas have emerged to explain the mechanisms of cadherin-mediated cell adhesion. Although different models were proposed for cadherin interactions, a consensus has come forth con...
10331247
Synthesis, structures and antitumor activity of the first crown ester-linked bipyridyl platinum complexes.
Three new crown ester-linked bipyridine homologs with three, four or five ethylene glycol units, which are bulky and soluble in both hydrophilic and lipophilic media, were synthesized. The reaction of the appropriate macrocycles with K2PtCl4 in water gave yellow cisplatin analogs in good yield. These complexes were con...
10234539
Influence of formulation technique for hydroxypropyl-beta-cyclodextrin on the stability of aspirin in HFA 134a.
The objective of this study was to determine the influence of the formulation technique for 2-hydroxypropyl-beta-cyclodextrin (HP beta CD) on the stability of aspirin in a suspension-based pressurized metered-dose inhaler (pMDI) formulation containing a hydrofluoroalkane (HFA) propellant. HP beta CD was formulated in a...
10230720
Activation of acyl-CoA cholesterol acyltransferase: redistribution in microsomal fragments of cholesterol and its facilitated movement by methyl-beta-cyclodextrin.
Acyl-CoA cholesterol acyltransferase (ACAT) (EC 2.3.1.26) in the yolk sac membrane of chicken eggs plays an important role in the transport of lipids, which serve as both structural components and as an energy source during embryogenesis. ACAT from the yolk sac membrane of chicken eggs 16 d after fertilization has high...
10228555
Eukaryotic glycosylation: whim of nature or multipurpose tool?
Protein and lipid glycosylation is a ubiquitous phenomenon. The task of cataloguing the great structural variety of the glycan part has demanded considerable efforts over decades. This patient endeavor was imperative to discern the inherent rules of glycosylation which cannot affirm assumptions on a purely coincidental...
10225368
Protection against ischemic damage by adenosine amine congener, a potent and selective adenosine A1 receptor agonist.
Although the selectivity and potency of adenosine amine congener (ADAC) at adenosine A1 receptors are similar to other highly selective agonists at this receptor type, the chemical structure of the N6 substituent is completely different. We now demonstrate that the characteristics of the therapeutic profile of ADAC are...
10220288
Effect of sugar-modified beta-cyclodextrins on dissolution and absorption characteristics of phenytoin.
Inclusion complexes of phenytoin (DPH) with 6-O-alpha-D-glucosyl (G1)- and 6-O-alpha-D-maltosyl (G2)-beta-cyclodextrins (beta-CyDs) were prepared in a molecular mixing ratio of 1:1. The advantages of these preparations in terms of dissolution characteristics and the oral absorbency of DPH were evaluated in comparison w...
10217532
Involvement of CB1 cannabinoid receptors in the EDHF-dependent vasorelaxation in rabbits.
1. It was recently suggested that an endogenous cannabinoid could represent an endothelium-derived hyperpolarizing factor (EDHF). The aim of the present study was to clarify whether CB1 cannabinoid receptors are involved in the nitric oxide (NO)- and prostanoid-independent vasodilation produced by acetylcholine in rabb...
10217526
In vitro prostanoid release from spinal cord following peripheral inflammation: effects of substance P, NMDA and capsaicin.
1. Spinal prostanoids are implicated in the development of thermal hyperalgesia after peripheral injury, but the specific prostanoid species that are involved are presently unknown. The current study used an in vitro spinal superfusion model to investigate the effect of substance P (SP), N-methyl-d-aspartate (NMDA), an...