PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “MACROMOLECULAR SYSTEMS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources
PubMed1994

Biological applications of atomic force microscopy.

The newly developed atomic force microscope (AFM) provides a unique window to the microworld of cells, subcellular structures, and biomolecules. The AFM can image the three-dimensional structure of biological specimens in a physiological environment. This enables real-time biochemical and physiological processes to be monitored at a resolution similar to that obtained for the electron microscope. The process of image acquisition is such that the AFM can also measure forces at the molecular level. In addition, the AFM can interact with the sample, thereby manipulating the molecules in a defined manner--nanomanipulation! The AFM has been used to image living cells and the underlying cytoskeleton, chromatin and plasmids, ion channels, and a variety of membranes. Dynamic processes such as crystal growth and the polymerization of fibrinogen and physicochemical properties such as elasticity and viscosity in living cells have been studied. Nanomanipulations, including dissection of DNA, plasma membranes, and cells, and transfer of synthetic structures have been achieved. This review describes the operating principles, accomplishments, and the future promise of the AFM.

Animals↗
PubMed1994

High-flow microinfusion: tissue penetration and pharmacodynamics.

High-flow microinfusion provides a means for delivering macromolecules to large volumes of brain in easily obtainable time intervals. Slowly degraded approximately 180-kDa macromolecules, delivered at a constant volumetric flow rate of 3 microliters/min into homogeneous brain tissue (e.g., gray matter), would penetrate to a 1.5-cm radius in 12 h. The predicted concentration profile is relatively flat until it declines precipitously at the flow front. Hence, tissues are dosed rather uniformly, providing control over the undesired toxicity that may occur with alternative methods that depend on large concentration gradients for tissue transport. The penetration advantage of high-flow (convective) over low-flow (diffusive) microinfusion has been assessed at fixed pharmacodynamic effect. A 12-h high-flow microinfusion of a macromolecule degraded with a characteristic time of 33.5 h would provide 5- to 10-fold increases in volume over low-flow infusion and total treatment volumes > 10 cm3. Slower degradation rates would result in larger treatment volumes; more rapid degradation rates would reduce the volume but still favor convective over diffusive administration. This technique may be applicable to a variety of diagnostic and therapeutic agents such as radioimmunoconjugates, immunotoxins, enzymes, growth factors, and oligonucleotides.

Animals↗
PubMed2002

Polymeric complexes of lidocaine hydrochloride with poly(acrylic acid) and poly(2-hydroxyethyl vinyl ether).

The specific interactions of local anesthetic lidocaine hydrochloride with poly(acrylic acid) and poly(2-hydroxyethyl vinyl ether), as well as in a triple system composed of the drug and both polymers, have been studied in aqueous solutions by viscometric, turbidimetric, potentiometric, and FTIR spectroscopic methods. The mechanism of the drug binding to the polymers and the structures of the polycomplexes formed are clarified.

Acrylic Resins↗
PubMed2006

Synthesis of core-shell Au@polypyrrole nanocomposite using a dendrimer-template approach.

Conducting polymeric nanostructures have been reported recently, which were produced from polypyrrole (PPy), including hollow nanocapsules, nanofibers, nanoporous membranes, nanowires, and nanofilms. In most cases, new synthetic routes were used aimed at controlling specific properties of these conducting nanostructures at the molecular level. In this communication we present a new chemical route to synthesize polypyrrole-based nanocomposites, in which polyamidoamine (PAMAM) dendrimers encapsulating Au nanoparticles are used as template. The two-step synthesis comprises the reduction of Au nanoparticles inside PAMAM molecules followed by PPy polymerization around the PAMAM-Au nanoparticles. The structure of the core-shell PAMAM-gold@polypyrrole nanospheres comprises a 40 nm PPy shell enclosing a core of 3 nm gold nanoparticles, as revealed by Transmission Electronic Microscopy (TEM). This new, environmentally-friendly approach may be suitable to produce hybrid nanomaterials for applications in catalysis, batteries, sensors, and micro/nanoelectronic devices.

Dendrimers↗
PubMed1988

Multiple ubiquitination of vertebrate calmodulin by reticulocyte lysate and inhibition of calmodulin conjugation by phosphorylase kinase.

Mammalian calmodulin containing trimethyllysine 115 can be covalently coupled to ubiquitin in a Ca2+-dependent manner in the presence of ATP/Mg2+ by reticulocyte lysate. This conjugation reaction can be quantitated in a novel test employing fluphenazine-Sepharose. It is shown that at least 3 ubiquitin molecules can be coupled to calmodulin indicating that more than one lysine residue is involved in the ubiquitination reaction. In addition only the free form of calmodulin can be ubiquitinated. Neither calmodulin bound to phosphorylase kinase as an integral subunit (delta-subunit) nor that bound as a peripheral subunit (delta'-subunit) is ubiquitinated. A total binding of equimolar calmodulin to phosphorylase kinase occurs since the affinity of binding of calmodulin to phosphorylase kinase as integral (KCaMm unknown) or peripheral subunit (KCaMm ca. 30-50nM) is several order of magnitude higher than the corresponding affinity of calmodulin for the ubiquitin-conjugating enzyme (KCaMm ca. 8 microM). We conclude that the "protective" effect of phosphorylase kinase towards calmodulin conjugation is due to a changed conformation of bound calmodulin and/or inacessibility of the ubiquitination sites (e.g. at subunit-subunit interface). Thus Ca2+-dependent ubiquitination only of free calmodulin may provide an efficient scavanging mechanism (with subsequent breakdown) for all free calmodulin in excess of that amount which can be bound by the calmodulin-binding proteins in the cell.

Adenosine Triphosphate↗
PubMed1996

Novel systems for controlled delivery of macromolecules.

Gene therapy promises new treatments for human disease by alterations in the DNA content of tissues. Methods for efficient and stable introduction of genes into target cells in the body are critically important in this effort. Researchers and physicians now have many years of experience with synthetic polymers for controlled drug delivery; many of these polymers can also be used to deliver macromolecules at controlled rates to tissues. This article reviews the use of polymers in controlled protein delivery and suggests ways that polymer delivery systems may be useful in the delivery of gene transfer agents.

Animals↗
PubMed1988

The role of renal macrophages in the aglomerular kidney of the sea-horse (teleost) in the removal of exogenous macromolecules from circulating blood.

Mechanisms involved in the removal of exogenous macromolecules from circulating blood were investigated in the aglomerular nephrons of the kidney of the sea-horse, Hippocumpus kuda Bleeker, using either native anionic or cationized probes. After intraperitoneal injection of native anionic horse-spleen ferritin (HS-AF) or cationized one (HS-CF) into the sea-horse, kidneys and gills were examined morphologically at intervals of 1 h to 14 days. Histochemical and immunohistochemical studies and transmission electron microscopy of the kidneys revealed that most of the injected HS-AF or HS-CF were taken up by macrophages in the sinusoids of hemopoietic tissue through pinocytosis, being gradually accumulated into their phagolysosomes. By the 14th day, the injected ferritin particles were degraded and the ferric agglomerates were concentrated within the phagolysosomes. Then the macrophages heavily laden with densely packed ferric catabolites migrated into the hemopoietic area forming macrophage agglomerates or macrophage centers. Some HS-AF and HS-CF particles infiltrated into the tubular basement membrane, where they were taken up by the tubular epithelial cells through pinocytosis, translocated into the phagolysosomes, fragmented into small ferric catabolites and then excreted into the urinary space. In contrast, examination of the gills revealed neither HS-AF, HS-CF particles nor their histochemically detectable ferric catabolites in either the interstitial space including basal lamina or the alveolar epithelia. It seems that no appreciable egress of exogenous substances occurs from the gill into the environmental water.

Animals↗
PubMed1997

Development of targeted delivery systems for nucleic acid drugs.

Our increased understanding of disease pathogenesis is the basis for developing novel nucleic acid drugs. The main challenge encountered in this development is how to maintain therapeutically meaningful concentrations of the drugs in the vicinity of their targets for the desired periods. The intrinsic difficulty arises from the fact that nucleic acid drugs are not readily transported across membranes. Hence, their delivery and transport characteristics at the whole body, organ and cellular levels need to be thoroughly examined. Liposomes and receptor-mediated polycation systems are promising carriers for their delivery in vivo. There are many barriers to be overcome for successful antisense and gene therapies. Along with other factors, disposition, stability against nucleases, binding to cell surface receptor and internalization, and intracellular trafficking affect the in vivo delivery and efficacy of nucleic acid drugs. This review article discusses the delivery and transport of these compounds.

Animals↗
PubMed2002

Drug delivery systems based on sugar-macromolecule conjugates.

The specificity of carbohydrate-protein interactions can greatly outstrip that of many other ligand-binding systems; such is the enormous density of information that sugars can convey. In addition, macromolecules allow for the fine-tuning of active drug delivery through their great ability to undergo site-specific modification and their inherent physicochemical properties. Once combined, these two factors suggest that sugar-macromolecule conjugates, targeted using endogenous carbohydrate binding proteins, are a promising route to the 'magic bullet'.

Animals↗
PubMed2006

[Advances in the investigation of biological effect and surface modification of dendrimers as drug (gene) delivery systems].

Dendrimers are highly branched macromolecules that have attractive nano-sized architectures. It seems that they can enter various cells easily because of their unique nanostructures and chemical properties, which make them to be one of important candidates of non-virus carriers for drug delivery or gene therapy. However, the understanding of cytotoxicity and related mechanisms of dendrimers are still limited. In recent years there has been rapid increases of researches regarding the biological effects of dendrimers, including the interactions of dendrimers to cells, transport mechanisms, intracellular distribution and biodistribution in vivo, as well as improvement of biocompatibility of dendrimers by surface engineering. In this paper, recent advances in the investigations of biological effect and surface modification for the dendrimers as drug or gene delivery systems were reviewed.

Animals↗
PubMed1989

[Dissociation of hexamers of cytochrome P-450 LM2 in the presence of the non-ionic detergent emulgin 913].

It was shown that the maximal degree of dissociation of cytochrome P-450 LM2 hexamers in the presence of the nonionic detergent Emulgene 913 (20 degrees C) is observed at the detergent concentration of about 0.2%. Using equilibrium centrifugation in solutions of different density, the molecular mass of the dissociation product minus that of the bound detergent was found to be equal to 50 +/- 8 kDa, thus corresponding to the molecular mass of the monomer. One cytochrome P-450 LM 2 molecule binds 80 +/- 20 molecules of Emulgene 913.

Centrifugation↗
PubMed1975

The active form of cytochrome P-450 from bovine adrenocortical mitochondria.

Cytochrome P-450 from bovine adrenocortical mitochondria exists in three forms of molecular weight: 850,000 (protein 16), of one-half (protein 8), and of one-quarter of this value (protein 4). The forms of the enzyme are named according to the number of subunits and all appear to be active in converting cholesterol to 3beta-hydroxy-5-pregnen-20-one (side chain cleavage) (Shikita, M., and Hall, P.F. (1973) J. Biol. Chem. 248, 5606). To determine whether all three forms are active at their characteristic molecular weights, the three cytochromes were each layered onto separate sucrose density gradients and centrifuged at 49,000 rpm for 60 min; the gradients contained all the factors necessary for side chain cleavage including one of the following substrates: cholesterol, 20S-hydroxycholesterol, and 20S,22R-dihydroxycholesterol. Regardless of the form of P-450 layered onto the gradient and regardless of the substrate, enzyme activity (side chain cleavage) was observed only in fractions corresponding to a sedimentation coefficient of 20 to 22 S which is that for protein 16. No activity was observed at S values corresponding to either protein 8 or protein 4. These findings indicate that the active form of cytochrome P-450 from adrenocortical mitochondria is that containing 16 subunits, i.e. the form in which the cytochrome is normally isolated from adrenal mitochondria. Forms consisting of eight and four subunits which can be prepared from protein 16 become active only by forming protein 16, at least in an aqueous medium in vitro.

Adrenal Cortex↗
PubMed1979

Hydrodynamic studies on interactions between the components of the liver microsomal cytochrome P-450 system.

To understand the different behaviour of cytochrome P-450 systems in kinetics as well as in the demethylase activity, sedimentation and molecular weight experiments have been carried out with the following results: 1) Sedimentation coefficients of solubilized P-450 and P-450 LM2 fractions amount to 24 +/- 4 [S] and 12.8 +/- 1.2 [S], respectively. Molecular weights were determined to be 1.0 +/- 0.2 . 10(6) and 3.0 +/- 0.5 . 10(5) Dalton. 2) Triton N-101 provokes splitting of the associated structure both of solubilized P-450 and P-450 LM2; this effect is reversible. 3) The dissociation depends not only on the absolute concentration of Triton but rather on the Triton P-450 ratio. The dissociation curves of solubilized P-450 and P-450 LM2 are similar in shape and in the Triton/P-450 ratio dependence. 4) In the presence of small concentrations of Triton a more complicated dissociation behaviour was observed with broad integral distribution of the sedimentation coefficients. 5) The ionic detergent cholate splits the associated structure of P-450 LM2 at considerably higher concentrations in comparison with Triton-N 101. 6) Addition of reductase causes a decrease of sedimentation coefficients and molecular weights of solubilized P-450. The same effect in P-450 LM2 could be observed only in the presence of phospholipids.

Animals↗
PubMed1983

Hydrodynamic studies on the association of cytochrome P-450.

Extended ultracentrifugation experiments have been performed on cytochrome P-450 LM2 from rabbit liver microsomes to analyse the behaviour of this membrane protein. The sedimentation coefficients and molecular weights vary between 11 S and 19 S and 350,000 and 700,000, respectively. No concentration dependence of these values could be observed between 0.3 microM 5.0 microM protein. The sedimentation coefficients and molecular weights appear to correlate with the heme content. Partial loss of heme leads to formation of aggregates of higher molecular weight. Analysis of the distribution of sedimentation coefficients clearly reveals the heterogeneity of the individual samples with values ranging from about 8 to 23 S. Thus, the smallest particle in the associate mixture of the enzyme consists of at most 3 monomers.

Animals↗