Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MACROMOLECULAR SYSTEMS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 901 records · Page 50Linked to original sources
PubMed2001

Studies of magnetization transfer and relaxation in irradiated polymer gels--interpretation of MRI-based dosimetry.

Magnetization transfer and NMR relaxation rates were measured for water protons in two types of polymer gels developed for radiation dosimetry with MRI in order to quantify the contributions of different relaxation processes to the radiation response in such gels. Measurements included the rate of magnetization transfer between proton pools and the ratio of the sizes of exchanging pools, R1 and R2. A model of relaxation in irradiated gels is presented to explain their properties. The model incorporates three proton pools: free water, macromolecular and interfacial. Two pools are insufficient to model the data. In these systems, radiation-induced polymerization appears to increase the size of a solid-like macromolecular proton pool but does not affect the rate constant of magnetization transfer per proton from macromolecular protons to the free water protons. The relation between R1 and the pool size ratio is consistent with free water exchanging with a macromolecular pool with an R1 of approximately 8 Hz. In addition, the rate of magnetization transfer is not limited by the rate of chemical exchange between the free water and the interfacial protons, and magnetization transfer most probably occurs via labile proton exchange rather than via bound water molecules.

Acrylamide↗
PubMed1984

The membranous epithelial (M) cell and the mucosal immune system.

Membranous epithelial (M) cells are specialized epithelial cells overlying the subepithelial lymphoid follicles in the gastrointestinal and respiratory tracts. Antigens, including some viruses and bacteria, penetrate the mucosal barrier via the M cell, which endocytoses and transports antigens and microorganisms into the Peyer's patch or bronchial-associated lymphoid tissue. Here antigens may initiate an immune response and/or disseminate and induce disease. This review discusses the structure and function of the M cell, its role in macromolecular uptake, and its interaction with the immune system.

Animals↗
PubMed2005

Transport ATPases: structure, motors, mechanism and medicine: a brief overview.

Today we know there are four different types of ATPases that operate within biological membranes with the purpose of moving many different types of ions or molecules across these membranes. Some of these ions or molecules are transported into cells, some out of cells, and some in or out of organelles within cells. These ATPases span the biological world from bacteria to eukaryotic cells and have become most simply and commonly known as "transport ATPases." The price that each cell type pays for transport work is counted in molecules of hydrolyzed ATP, a metabolic currency that is itself regenerated by a transport ATPase working in reverse, i.e., the ATP synthase. Four major classes of transport ATPases, the P, V, F, and ABC types are now known. In addition to being involved in many different types of biological/physiological processes, mutations in these proteins also account for a large number of diseases. The purpose of this introductory article to a mini-review series on transport ATPases is to provide the reader with a very brief and focused look at this important area of research that has an interesting history and bears significance to cell physiology, biochemistry, immunology, nanotechnology, and medicine, including drug discovery. The latter involves potential applications to a whole host of diseases ranging from cancer to those that affect bones (osteoporosis), ears (hearing), eyes (macromolecular degeneration), the heart (hypercholesterolemia/cardiac arrest,), immune system (immune deficiency disease), kidney (nephrotoxicity), lungs (cystic fibrosis), pancreas (diabetes and cystic fibrosis), skin (Darier disease), and stomach (ulcers).

ATP-Binding Cassette Transporters↗
PubMed1986

Heterogeneity of intimal and microvessel endothelial cell barriers in vitro.

We have compared the barriers provided by bovine aortic endothelial cells (AEC), cerebral microvessel endothelial cells (CMEC), and pulmonary microvessel endothelial cells (PMEC) cultured on microcarriers to the passage of trypan blue-bovine serum albumin (TB-BSA). AEC and PMEC barriers were quantitatively comparable, and significantly more permeable to TB-BSA than the CMEC barrier. Serotonin, norepinephrine, and histamine, shown to modulate the AEC barrier, had no effect on the CMEC barrier to TB-BSA. These results suggest that cultured endothelial cells (EC) retain region-specific phenotypic modifications of barrier function observed in vivo. Glutaraldehyde-fixed EC and EC kept at 4 degrees C to minimize transcytosis displayed TB-BSA passage that was reduced by less than 30%, which indicated that the bulk of tracer movement occurred via diffusion between EC. Treatment with cytochalasin B (5 micrograms/ml) resulted in significant AEC and CMEC barrier loss. These results suggest that microfilament bundles are involved in maintaining EC close junctional apposition. We have reported previously that exogenous serotonin and norepinephrine stimulate the EC barrier function in vivo and in vitro, and modulate EC motility, shape, and stress fiber assembly in vitro. In light of these data and the present results, we hypothesize that EC motility and shape change determine in part intercellular macromolecular diffusion by way of a dynamic system of pores of varying radii.

Analysis of Variance↗
PubMed2006

Bacterial adhesion and entry into host cells.

Successful establishment of infection by bacterial pathogens requires adhesion to host cells, colonization of tissues, and in certain cases, cellular invasion-followed by intracellular multiplication, dissemination to other tissues, or persistence. Bacteria use monomeric adhesins/invasins or highly sophisticated macromolecular machines such as type III secretion systems and retractile type IV pili to establish a complex host/pathogen molecular crosstalk that leads to subversion of cellular functions and establishment of disease.

Bacteria↗
PubMed2002

Imaging and manipulation of biological structures with the AFM.

Many biologists have dreamt of physically touching and manipulating the biomolecules they were investigating. With the invention of the atomic force microscope (AFM), this dream has come true. Here, recent applications of the AFM to image and to manipulate biological systems at the nanometer scale are reviewed. Macromolecular biological assemblies as well as individual biomolecules can be subjected to controlled nanomanipulation. Examples of AFM application in imaging and nanomanipulation include the extraction of chromosomal DNA for genetic analysis, the disruption of antibody--antigen bonds, the dissection of biological membranes, the nanodissection of protein complexes, and the controlled modulation of protein conformations. Also reviewed is the novel combination of single molecule imaging and force spectroscopy which allows biomolecules to be imaged, and inter- and intramolecular forces to be measured. Future application of these nanotechniques will reveal new information on the structure, function and assembly of biomolecules.

Antigen-Antibody Complex↗
PubMed1974

Transfer of newly synthesized proteins from Schwann cells to the squid giant axon.

The squid giant axon is presented as a model for the study of macromolecular interaction between cells in the nervous system. When the isolated giant axon was incubated in sea water containing [(3)H]leucine for 0.5-5 hr, newly synthesized proteins appeared in the sheath and axoplasm as demonstrated by: (i) radioautography, (ii) separation of the sheath and axoplasm by extrusion, and (iii) perfusion of electrically excitable axons. The absence of ribosomal RNA in the axoplasm [Lasek, R. J. et al. (1973) Nature 244, 162-165] coupled with other evidence indicates that the labeled proteins that are found in the axoplasm originate in the Schwann cells surrounding the axon. Approximately 50% of the newly synthesized Schwann cell proteins are transferred to the giant axon. These transferred proteins are soluble for the most part and range in molecular size from 12,000 to greater than 200,000 daltons. It is suggested that proteins transferred from the Schwann cell to the axon have a regulatory role in neuronal function.

Animals↗
PubMed2006

Fucosphere--new microsphere carriers for peptide and protein delivery: preparation and in vitro characterization.

PURPOSE: Fucoidan is a complex polysaccharide containing sugars and high amounts of sulphate derived from marine brown algaes. In this study, a new microsphere-delivery system based on cross-linking of fucoidan with chitosan, named Fucosphere, was evaluated as a drug carrier. Bovine serum albumin (BSA) was used as a model protein. The effect of fucoidan (1.5, 1.75, 2.0 and 2.5%), chitosan (0.25, 0.50 and 0.75%) and protein (0.25, 0.50 and 0.75%) concentrations, the origin of chitosan and the preparation methods of the particles on the microsphere characteristics were evaluated. METHODS: The microspheres were prepared by a simple method based on the cross-linking of the opposite charged biopolymers. The shape and surface morphologies of the particles were evaluated by scanning electron microscopy (SEM) and the size, charge and encapsulation capacity of the microspheres were determined. The released amount of BSA from the microspheres into phosphate buffered saline (PBS pH 7.4) was determined spectrophotometrically by the Bradford method. SDS-PAGE was performed to check the structural integrity of BSA after the preparation. RESULTS: Smooth and spherical microspheres between the size ranges of 0.61-1.28 microm were obtained. BSA was efficiently encapsulated into the microspheres (51.8-89.5%). All formulation parameters affected the encapsulation capacity of Fucosphere (p < 0.05). The highest encapsulation was obtained with microspheres containing 2.5% of fucoidan (89.5%). CONCLUSIONS: The extent of drug release from the microspheres was dependent on the concentrations of polymers and BSA, chitosan origin and type of preparation method. When the addition methods of protein compared, BSA encapsulated into Fucosphere released slower than the adsorbed protein (E) (p < 0.05). The electrophoretic mobility values of Fucospheres changed between +6.9 and +32.3 mV. In general, BSA release from Fucosphere showed a three-phasic release curve. In conclusion, this new fucoidan microsphere system may be a potential delivery of macromolecular drug such as peptide and protein.

Animals↗
PubMed1974

Induction of aryl hydrocarbon (benzo(a)pyrene) hydroxylase and tyrosine aminotransferase in hepatoma cells in culture.

In the Reuber (H35) hepatoma cell strain, microsomal aryl hydrocarbon (benzo[a]pyrene) hydroxylase is induced 25-fold by the polycyclic hydrocarbon benz[a]anthracene but is not induced by the steroid hormone dexamethasone. Soluble tyrosine aminotransferase is induced sixfold by dexamethasone and twofold by benz[a]anthracene. Each enzyme requires similar inducer concentrations for induction, and their induction kinetics are similar. The induction of each enzyme requires RNA and protein synthesis; in each case the transcriptional and translational steps can occur independently. The two induction systems are differentially sensitive to inhibitors of macromolecular synthesis. Simultaneous exposure to both inducers produces increases in both enzyme activities that are greater than those produced by either inducer alone. Each inducer acts at a pretranslational level to produce this synergistic effect. The results suggest that the requirements for macromolecular synthesis are similar for the induction of each enzyme, but that the turnover of enzyme-specific macromolecules may differ for each.

Animals↗
PubMedDate not supplied

Alfimeprase: pharmacology of a novel fibrinolytic metalloproteinase for thrombolysis.

Alfimeprase is a recombinantly produced, truncated form of fibrolase, a known directly fibrinolytic zinc metalloproteinase that was first isolated from the venom of the southern copperhead snake (Agkistrodon contortrix contortrix). Both fibrolase and alfimeprase have been shown to have direct proteolytic activity against the fibrinogen Aalpha chain. In vivo pharmacology studies have shown that thrombolysis with alfimeprase is up to 6 times more rapid than with plasminogen activators. Alfimeprase can be bound and neutralized by serum alpha(2)-macroglobulin, a prevalent mammalian protease inhibitor which is capable of forming a macromolecular complex with alfimeprase. As a result, systemic bleeding complications have been greatly reduced due to the inhibitory effects of alpha(2)-macroglobulin. This article reviews the biochemical in vitro and in vivo characteristics of this novel acting thrombolytic.

Animals↗
PubMedDate not supplied

[Highest level of division in the organism classification. 1. Prokaryotes and eukaryotes].

The works on the general classification of all organisms are considered as a convenient opportunity to sum up numerous data obtained in organic world studying. The present stage is characterized by rapid development of the molecular reconstructions that have already caused considerable changes in our classification practice. These changes look especially impressive at studying the organism cellular structure. The great massive of new data allow us to compare Prokaryotes and Eukaryotes on the nucleic acids and especially proteins whose number in Eukaryote cell approaches to several thousands. Basing on the structure of macromolecules one can hypothesize with great certainty about Prokaryote or Eukaryotes origin. The article presents the detailed characteristic of Prokaryotes or Eukaryotes with the emphasis placed on the comparative analysis of biological macromolecules. Among specially considered cellular structures and processes are cell wall, intracellular components, cellular cycle, nucleus, DNA compactness, replication, genome organization, transcription, posttranscriptional modifications, introns, ribosomes and translation, cytoskeleton, mitosis, cytokinesis, cellular organelles, intracellular membranes systems, modes of nutrition, sexual condition. The macromolecular analysis let to carry out the homology of structures and to find out some new connections. It was shown that typology considered as a search for morphological patterns within the biodiversity structure has almost exhausted the subject. It was directed mostly to distinguishing "main" group in contrast with intermediate and aberrant ones, which were considered as minor phenomenon. At present due to macromolecules systematics it is able to estimate the whole diversity of forms including typologically transitive.

Biodiversity↗
PubMed1985

[Tumor-targeted chemotherapy with lipid contrast medium and macro molecular anticancer agents theoretical considerations and clinical outcome].

Theoretical considerations for tumor-selective chemotherapy are described which based on the unique character of the tumor neovasculature. Namely, most solid tumors possess four different unique features: hypervasculature, enhanced permeability even to macromolecules, architectural differences, and lack of the lymphatic recovery system. Lipid or lipid contrast medium and macromolecular anticancer agents using prototype drug smancs can be utilized for cancer-selective targeting based on the above four features. Selective targeting with lipid contrast medium with smancs has offered two clinical benefits; definite and pronounced antitumor effect and diagnostic value. These effects can be primarily attributed to the tumor-selective accumulation of the agent, i.e., more than 1,000 times greater in the tumor than in the plasma. As a consequence very few side effects are observed clinically. Primary or secondary hepatoma and lung cancer showed size reduction in more than 90 % of treated patients. Very few side effects such as hematosuppression or inhibited liver function were observed in these cases. Prolongation of life-span was marked in the patients. The above results indicate a new future direction for the development of the tumor-selective chemotherapy.

Animals↗
PubMed1986

Thoughts and studies on purification of the angiotensin II receptor.

The angiotensin receptor is the only macromolecular component of the renin-angiotensin system which has not yet been purified and characterized in the isolated state. A purified preparation could be useful for identifying the amino acid residues it preferentially recognizes in various positions of defined peptide ligands, and for elucidating the proximate molecular mechanism by which the binding event is transduced into a cellular response. Such knowledge should expedite the development of receptor antagonists which might be more physiologically specific than other inhibitors of the system. This paper elaborates on these thoughts, and describes some recent progress in purification of the rabbit hepatic receptor.

Angiotensin Receptor Antagonists↗
PubMed1984

Macromolecular charge and reticuloendothelial function: comparison between the kinetics of administered native and cationized ferritins and the corresponding immune complexes in the mouse.

In order to evaluate the role of macromolecular charge on uptake by the reticuloendothelial system (RES), kinetic studies were carried out following the intravenous administration of 125I-labelled native ferritin (NF, pI 4.5) or cationized ferritin (CF, pI 7) to Swiss-Webster female mice subsequently killed at 2, 4, 8, 24 and 36 hr later. The same experiments were performed following the administration of radio-labelled (125I) native ferritin immune complexes (NFIC, pI 5-6.5) and cationized ferritin immune complexes (CFIC, pI 6.5-7.5). These complexes were prepared in five-times antigen excess by combination of affinity-purified anti-ferritin IgG-125I with NF or CF. A striking difference between the plasma clearance of NF and that of CF was observed in that the former was rapidly eliminated within 8 hr whereas the latter persisted in the circulation at 24 hr. This was associated with a significant increase in the uptake of NF by the liver, spleen, and kidney. No differences were observed in blood cell-associated radioactivity. Immunohistochemical studies confirmed the presence of increased amounts of NF in Kupffer cells and splenic phagocytes. Thus, the uptake of ferritin by components of the RES is highly dependent upon its pI. The present data may be explained by differences in diffusibility of CF and NF or alternatively by differential interactions with the cell surface in vivo. Contrary to the prior investigation carried out with the antigens alone, the plasma clearance and organ (liver, spleen and kidney) kinetic studies of NFIC and CFIC were similar. In addition, immunohistochemical studies demonstrated that the uptakes of NFIC (pI 5-6.5), CFIC (pI 6.5-7.5) and CFIC (pI 7-9) by Kupffer cells and splenic phagocytes were similar. As further confirmation for similarity in binding to Fc receptors of human polymorphonuclear leucocytes, Scatchard analysis failed to demonstrate any differences between NFIC and CFIC. These studies provide evidence that, within the range employed in this investigation, the charge of ferritin within the immune complex (and hence the charge of the complex itself) does not affect its uptake by receptors of phagocytic cells. In contrast, the uptake of ferritin, which is not Fc or C3 receptor dependent, is clearly conditioned by electrostatic charge.

Animals↗
PubMed1996

Strategies for the isolation and purification of retroviral vectors for gene therapy.

Viral gene therapy vectors promise new opportunities for treatment of hitherto debilitating and life threatening illnesses. To enable early and rapid clinical evaluation of the therapeutic potential of the technology, the initial objectives of process development have so far largely concerned vector assembly, product quality and safety, and manufacturing consistency appropriate to modest scales. The first of such vectors are under test in clinical trials approved through the regulatory CTX/IND route and thus conform to the standards specified for purity and contaminant removal. Process optimisation, scale-up and operability have been of secondary concern and the establishment of a scientific basis for the mechanistic development of future vector manufacturing processes has yet to be seriously addressed. This review considers the manufacturing demands of retroviral vectors and the candidate separation technologies which could facilitate preparation of clinical grade materials. Note is made that the practising community appears to place implicit confidence in the capability of conventional membranes and chromatographic supports developed for protein purification to perform adequately for large-scale purification of viruses. In particular, these are expected to deliver virus preparations to product standards currently required of therapeutic proteins. It is argued that the basis for this confidence may be ill-placed, since the physical and chemical characteristics of viral particles differ significantly from macromolecular proteins. The specific requirements for separation systems and materials for processing of retroviral vectors are considered, and specific routes to more efficient manufacturing processes are proposed.

Animals↗
PubMed1989

Elevated levels of the alpha subunit of GTP-binding protein Go in cerebrospinal fluid of patients with neurological disorders.

By employing a highly sensitive immunoassay method, concentration of the alpha subunit of GTP-binding protein, Go (Go alpha), recently shown to be localized mainly in nervous tissues and neuroendocrine cells, was determined in cerebrospinal fluids (CSF) of 192 patients with various neurological disorders and 50 control subjects. The results were compared with CSF levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) in the same samples. Normal levels of Go alpha were 51.9 +/- 21.7 pg/ml. The levels of Go alpha, as well as NSE and S-100b, in CSF were enhanced in some patients with acute conditions, e.g., meningitis (48%), encephalitis (100%), and cerebral infarct (56%). In these disorders, cases with enhanced Go alpha levels were more frequent than those with enhanced NSE or S-100b. Three patients with encephalitis whose Go alpha levels were more than 1000 pg/ml all died; the remaining two patients with encephalitis and slightly elevated Go alpha levels had a good prognosis. Concentration of Go alpha in CSF correlated well with that of NSE but poorly with that of S-100b. However, cervical spondylosis and demyelinating diseases, CSF levels of Go alpha were generally lower than those of NSE or S-100b. These results suggest that Go alpha in CSF is a useful marker for monitoring patients with acute neuronal damage. Since these three proteins are distributed differently in the central nervous system, simultaneous determination of Go alpha, NSE, and S-100b levels in CSF might provide valuable information about the pathophysiology of neurological disorders.

Biomarkers↗
PubMed1995

Developmental expression of heterotrimeric G proteins in the nervous system of Manduca sexta.

The heterotrimeric G proteins are a conserved family of guanyl nucleotide-binding proteins that appear in all eukaryotic cells but whose developmental functions are largely unknown. We have examined the developmental expression of representative G proteins in the developing nervous system of the moth Manduca sexta. Using affinity-purified antisera against different G alpha subunits, we found that each of the G proteins exhibited distinctive patterns of expression within the developing central nervous system (CNS), and that these patterns underwent progressive phases of spatial and temporal regulation that corresponded to specific aspects of neuronal differentiation. Several of the G proteins examined (including Gs alpha and G(o) alpha) were expressed in an apparently ubiquitous manner in all neurons, but other proteins (including Gi alpha) were ultimately confined to a more restricted subset of cells in the mature CNS. Although most of the G proteins examined could be detected within the central ganglia, only G(o) alpha-related proteins were seen in the developing peripheral nerves; manipulations of G protein activity in cultured embryos suggested that this class of G protein may contribute to the regulation of neuronal motility during axonal outgrowth. G(o) alpha-related proteins were also localized to the developing axons and terminals of the developing adult limb during metamorphosis. These intracellular signaling molecules may, therefore, play similar developmental roles in both the embryonic and postembryonic nervous system.

Amino Acid Sequence↗