Heterogeneous nature of microalbuminuria in NIDDM: studies of endothelial function and renal structure

Glutathione-related enzymes are thought to influence the prognoses of patients with adenocarcinoma of the lung. In this study, the localization of these enzymes was examined immunohistochemically in the primary lesions and metastatic lymph nodes of 61 patients with primary adenocarcinoma. Strong immunoreactivity for glutathione peroxidase (GSH-PO) and superoxide dismutase (SOD) was found in tissue from patients with poor prognoses, while tissue from patients with favorable prognoses demonstrated only immunoreactivity for these enzymes. Therefore, believe that glutathione-related enzymes may serve as predictors of tumor resistance in patients with adenocarcinoma, hence measuring these enzymes may be useful in determining the need for adjuvant therapy.     

CFTR: domains, structure, and function

Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) (Collins, 1992). Over 500 naturally occurring mutations have been identified in CF gene which are located in all of the domains of the protein (Kerem et al., 1990; Mercier et al., 1993; Ghanem et al., 1994; Fanen et al., 1992; Ferec et al., 1992; Cutting et al., 1990). Early studies by several investigators characterized CFTR as a chloride channel (Anderson et al.; 1991b,c; Bear et al., 1991). The complex secondary structure of the protein suggested that CFTR might possess other functions in addition to being a chloride channel. Studies have established that the CFTR functions not only as a chloride channel but is indeed a regulator of sodium channels (Stutts et al., 1995), outwardly rectifying chloride channels (ORCC) (Gray et al., 1989; Garber et al., 1992; Egan et al., 1992; Hwang et al., 1989; Schwiebert et al., 1995) and also the transport of ATP (Schwiebert et al., 1995; Reisin et al., 1994). This mini-review deals with the studies which elucidate the functions of the various domains of CFTR, namely the transmembrane domains, TMD1 and TMD2, the two cytoplasmic nucleotide binding domains, NBD1 and NBD2, and the regulatory, R, domain.     

Band 3 protein: physiology, function and structure

Band 3 protein is a typical polytropic membrane protein and mediates the exchange of the cellular HCO3- with CI- in plasma, which has been known as the "Chloride Shift". Owing to the "Chloride Shift", red blood cells can discriminate the metabolically active cells from inactive cells and deliver oxygen particularly to metabolically active tissues that produce carbon dioxide. Thus, band 3 protein is a sensor for metabolically active tissues and no excess oxygen is supplied to tissues as far as oxygen is delivered by red blood cells. In this chapter, we review the physiological role of the anion exchange mediated by band 3 protein and our work concerning the structure and function relationship in band 3 protein, that, is, affinity labeling of the active center for the anion exchange with pyridoxal phosphate, conformational change during the anion exchange process, examination of fidelity of hydropathy prediction on band 3 protein, and phosphoenolpyruvate transport mediated by band 3 protein and its clinical application.     

Guinea-pig vocalizations: their structure, causation and function

A colony of approximately 150 adult and infant guinea-pigs was studied in order to investigate the structure, causation and function of guinea-pig vocalizations. Behaviour and sound recording were made in a wide variety of contexts and sounds were analysed on the Kay Electric Sonagraph 6061 B. Sonagrams were measured, and on the basis of physical structure alone, 11 call types were distinguished. Behavioural records were examined and it was suggested that 5 functional categories existed. The significance of vocal communication in guinea-pig social behaviour was discussed.     

Band 3 protein: structure, flexibility and function

The oxidation of antibody carbohydrate residues is a common approach used for site-specific antibody immobilization or modification. In this study a flow injection analysis system (FIA) was developed for monitoring antibody oxidation. Antibodies were oxidized with periodate and the resulting aldehyde groups were labeled with Lucifer yellow CH (LyCH). The labeled antibodies were then injected onto an FIA system where the amount of LyCH label was determined by absorbance measurements at 428 nm and the amount of antibody was determined using an on-line bicinchoninic acid protein assay. The analysis time was 2 min per 20 microliters sample injection. The limits of detection for rabbit immunoglobulin G (IgG) and LyCH were 1 x 10(-8) and 4 x 10(-7) M, respectively. The dynamic ranges for IgG and LyCH extended to 2 x 10(-5) and 7 x 10(-3) M. The within-run precision was +/- 5% or less for both analytes. Studies with known LyCH/antibody mixtures indicated that the FIA system had greater accuracy than manual methods at high LyCH levels. One specific application studied for this system was its use in monitoring the time course of periodate-antibody oxidation.     

Cyclic nucleotide phosphodiesterases: diversity, classification, structure and function

PURPOSE: The effects of anti-inflammatory non-steroidal therapy combined with free-radical scavengers were studied and compared to corticosteroid use in the treatment of experimental corneal injury. METHOD: Eighty New Zealand albino rabbits were used in this study. A corneal alkali burn was induced by applying 1-N NaOH filter paper on the central axis of the right cornea for 30 s. Animals were distributed into five treatment groups: group 1 (control group) was only given gentamicin; group 2 was treated with 0.5% dimethylthiourea (DMU); group 3 received 1% dexamethasone; group 4 was given combined 0.5% DMU and 1% indomethacin; group 5 was treated with 0.5% DMU and 0.1% diclofenac sodium. One 50-microliter drop of gentamicin was instilled every 12 h, whereas the other drugs were instilled every 6 h (50 microliters). All groups received the same antibiotic treatment as the control group. The animals were killed on the 5th day. Inflammatory index, area and perimeter of the wounded corneal zone, and corneal transparency were evaluated. RESULTS: No significant differences in the inflammatory index were found between the treatment groups and the control group after 72 h. Significant differences (p < 0.001) were observed at 24 h in groups 3-5 when compared with the control group. Planimetry showed significant differences in group 4 when compared with the other groups (p < 0.05). Corneal transparency study showed statistically significantly better values in groups 4 and 5, when compared with the other groups, including group 3 (p < 0.05). CONCLUSIONS: The use of 0.5% DMU combined with 1% indomethacin can be considered an alternative to corticosteroid treatment in our experimental chemical corneal injury.     

Cancer-associated glycosphingolipid antigens: their structure, organization, and function

Experimental and human cancers are often characterized by the presence of tumor-associated glycosphingolipid (GSL) antigens defined by monoclonal antibodies. Major progress has been made during the past two decades on structural identification of these antigens. None of these structures are truly 'tumor-specific'. However, many of the antibodies show preferential or 'specific' reactivity with tumors, based on organizational differences of membrane GSLs in tumor cells versus normal cells. Clustered GSL antigens organized with transducer molecules in microdomain have been found recently to comprise a structural and functional unit involved in tumor cell adhesion coupled with signal transduction. Some of the GSL antigens have been identified as adhesion molecules recognized by carbohydrate-binding proteins or by complementary carbohydrates on target cells. Such adhesion, coupled with signaling, may initiate the metastatic process. Elucidating the mechanism of this initial adhesion/signaling step may lead to discovery of therapeutic agents that disrupt adhesion ('antiadhesion therapy') or normalize signaling ('ortho-signaling therapy'). Tumor-associated GSL antigens are also a target in immunotherapy of tumors, including development of antitumor vaccines.     

Granule-bound starch synthase: structure, function, and phylogenetic utility

Interest in the use of low-copy nuclear genes for phylogenetic analyses of plants has grown rapidly, because highly repetitive genes such as those commonly used are limited in number. Furthermore, because low-copy genes are subject to different evolutionary processes than are plastid genes or highly repetitive nuclear markers, they provide a valuable source of independent phylogenetic evidence. The gene for granule-bound starch synthase (GBSSI or waxy) exists in a single copy in nearly all plants examined so far. Our study of GBSSI had three parts: (1) Amino acid sequences were compared across a broad taxonomic range, including grasses, four dicotyledons, and the microbial homologs of GBSSI. Inferred structural information was used to aid in the alignment of these very divergent sequences. The informed alignments highlight amino acids that are conserved across all sequences, and demonstrate that structural motifs can be highly conserved in spite of marked divergence in amino acid sequence. (2) Maximum-likelihood (ML) analyses were used to examine exon sequence evolution throughout grasses. Differences in probabilities among substitution types and marked among-site rate variation contributed to the observed pattern of variation. Of the parameters examined in our set of likelihood models, the inclusion of among-site rate variation following a gamma distribution caused the greatest improvement in likelihood score. (3) We performed cladistic parsimony analyses of GBSSI sequences throughout grasses, within tribes, and within genera to examine the phylogenetic utility of the gene. Introns provide useful information among very closely related species, but quickly become difficult to align among more divergent taxa. Exons are variable enough to provide extensive resolution within the family, but with low bootstrap support. The combined results of amino acid sequence comparisons, maximum-likelihood analyses, and phylogenetic studies underscore factors that might affect phylogenetic reconstruction. In this case, accommodation of the variable rate of evolution among sites might be the first step in maximizing the phylogenetic utility of GBSSI.     

Foundations of genetics: genetic structure, function, and therapeutics

Molecular genetics provides the basis for understanding patterns of health and disease in people and is part of the scientific foundation on which acute and critical care nurses should build their practice. The human genome, defined as all the genetic information in the cells of humans, provides the blueprint for protein production and cellular function in the body. Alterations in protein production may result in illness or organ malfunction that has a genetic derivation. One therapeutic strategy that holds promise to manage genetic diseases is gene therapy. Gene therapy, or human gene transfer, occurs when scientists or physicians modify the genetic material in cells for therapeutic purposes. Genetic structure, function, and therapeutic reflect the science of the present and future and have profound practice implications for acute and critical care nurses.     

Aminopeptidases: structure and function

Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or peptide substrates. They are widely distributed throughout the animal and plant kingdoms and are found in many subcellular organelles, in cytoplasm, and as membrane components. Several aminopeptidases perform essential cellular functions. Many, but not all, of these peptidases are zinc metalloenzymes and are inhibited by the transition-state analog bestatin. Some are monomeric, and others are assemblies of relatively high mass (50 kDa) subunits. cDNA sequences are available for several aminopeptidases, and a 3-dimensional structure is available for the bovine lens enzyme. Crystallographic, electron micrographic, NMR, and photoaffinity labeling studies indicate that lens leucine aminopeptidase protomers are bilobal and that bestatin and substrates are bound in an active site, which is found in the larger lobe on each protomer. Zn2+ is involved in substrate liganding in most aminopeptidases. There is no evidence of an acyl-enzyme intermediate in hydrolysis. Amino acid sequences determined directly or deduced from cDNAs indicate some amino acid sequence homologies in organisms as diverse as Escherichia coli and mammals, particularly in catalytically important residues or in residues involved in metal ion binding.     

Chemokine receptors: structure, function and role in microbial pathogenesis

The chemokine superfamily is composed of at least 20 different leukocyte chemoattractants that act by binding to a family of G protein-coupled receptors. Leukocyte subtypes respond preferentially to unique but overlapping subsets of chemokines as determined by the receptor distribution, yet the receptors appear to signal through a common Gi-type G protein. Since chemokines appear to play major roles in inflammatory pathology, their receptors may be good targets for developing leukocyte selective anti-inflammatory drugs. Two chemokine receptors, CC CKRS and ONCC, function pathologically as cell entry factors respectively for human immunodeficiency virus 1, the cause of AIDS, and Plasmodium vivax, the major cause of malaria.     

Ribozymes: structure, function, and potential therapy for dominant genetic disorders

Some dominant genetic disorders, viral processes and neoplastic disorders base their pathogenicity on the production of protein or proteins that negatively affect cellular metabolism or environment. Thus, the inhibition of the synthesis of those proteins should prevent the biological damage. A promising approach to decreasing the level of the abnormal protein(s) is represented by specific interference with gene expression at the level of mRNA. The specific suppression of the expression of an mRNA can be achieved by using ribozymes. Ribozymes are RNA molecules able to break and form covalent bonds within a nucleic acid molecule. These molecules, with even greater potential advantages than antisense oligodeoxynucleotides, are able to bind specifically and cleave an mRNA substrate. There are advantages to using ribozymes instead of antisense oligodeoxynucleotides. Ribozymes can inactivate the target RNA without relying on the host cell's machinery and they have the capacity to cleave more than one copy of the target RNA by dissociating from the cleavage products and binding to another target molecule. Most of the studies performed to date have described the use of ribozymes as therapeutic agents for viral and cancer diseases. However, some dominant genetic disorders may also benefit from this approach. This is the case for some connective tissue disorders such as osteogenesis imperfecta, Marfan syndrome and the craniosynostotic syndromes.     

Na, K-ATPase--its structure, function and intracellular transport

Na, K-ATPase is an integral plasma membrane protein and plays essential roles such as maintaining sodium and potassium ion gradients across the plasma membrane. The enzyme consists of the alpha and the beta subunits with the stoichiometry of one to one. Three alpha subunit and two beta subunit isoforms have been detected in animal cells with the tissue-specific expression of both subunits. Recent advances in molecular biological studies on the Na, K-ATPase enable us to understand the structure-function relationships and mechanisms of intracellular transport of the enzyme. In this article we review the findings deduced from these studies, especially on the assembly and transport to the plasma membrane of the alpha and beta subunits.     

Phospholamban: protein structure, mechanism of action, and role in cardiac function

A comprehensive discussion is presented of advances in understanding the structure and function of phospholamban (PLB), the principal regulator of the Ca2+-ATPase of cardiac sarcoplasmic reticulum. Extensive historical studies are reviewed to provide perspective on recent developments. Phospholamban gene structure, expression, and regulation are presented in addition to in vitro and in vivo studies of PLB protein structure and activity. Applications of breakthrough experimental technologies in identifying PLB structure-function relationships and in defining its interaction with the Ca2+-ATPase are also highlighted. The current leading viewpoint of PLB's mechanism of action emerges from a critical examination of alternative hypotheses and the most recent experimental evidence. The potential physiological relevance of PLB function in human heart failure is also covered. The interest in PLB across diverse biochemical disciplines portends its continued intense scrutiny and its potential exploitation as a therapeutic target.     

Review of Attitudes: Their structure, function, and consequences.

Reviews the book, Attitudes: Their structure, function, and consequences edited by Russell H. Fazio and Richard E. Petty (see record 2007-02438-000). Fazio and Pety developed a text of key readings on attitude structure, function, and outcomes. Indeed, the size of the literature under review led the editors to divide the work into two sections: one text targeting attitude structure and function and a second (forthcoming) volume targeting the attitudes and persuasion literature. The text we are reviewing is the first in this two-volume set. Despite the difficulty of the task Fazio and Petty set for themselves, the result is a book that is appropriate for an audience ranging from the advanced undergraduate to the professional academic. (PsycINFO Database Record (c) 2010 APA, all rights reserved)