| 11753505 |
Oxytocinase as the most important marker of fetal development |
None |
Early Pregnancy (Cherry Hill) |
Oxytocinase as the most important marker of fetal development
Abstract
- Enzymes as biochemical markers come within the entire scope of the live mother-fetus system. The most important are the enzymes which regulate physiological processes, of which oxytocinase (a type of aminopeptidase) has a much wider scope of action than its name suggests, as it regulates also the level of aminopeptide hypothalamic hormones. Thus, it determines neurological, endocrinological and immunological regulation of entire steroidogenesis. Under the influence of gestational enlargement of the uterine cavity, the mothers hypothalamus produces an increasing amount of hormones, which in turn induces an increasing oxytocinase synthesis in the placenta in order to prevent the hormone in the blood reaching the level which could bring about uterine contractions. Also, the growing fetus additionally induces the production of oxytocinase by releasing its own hormones. All this occurs in combined action of the mother, fetus, placenta and even fetal membranes in one space-time process called pregnancy. When in the late pregnancy the enzyme remains at constant level or decreases without appearance of uterus contractions, labour induction is necessary due to fetus life hazard of as much as several percent. Reduction in enzyme level and even its insufficient growth in the second trimester of pregnancy, occur several weeks before preterm birth or death of the fetus. On the other hand, in the event of treatment of diseases accompanying the pregnancy,normalization of oxytocynasaemia shows the effectiveness of treatment. With the dominating profile of the steady increase of oxytocinase (>90% of cases), the target values are higher than in the case of irregular growth. Their close values are a result of the hormonal treatment of threatened pregnancies with ACTH depot. In the cases of the primary hypothalamic insufficiency, this treatment reduces the rate of fetal deaths, which would stand at several dozen percent. It is a classical example of biological pregnancy monitoring since the risk of fetal death can be predicted several weeks earlier when assessment of chemical compounds or physical changes still gives accurate results within physiological limits.
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| 11754596 |
Isomalabaricane-type nortriterpenoids and other constituents of the marine sponge Geodia japonica |
10.1021/np0100789. |
J Nat Prod |
Isomalabaricane-type nortriterpenoids and other constituents of the marine sponge Geodia japonica
Abstract
- Twelve compounds were isolated from the sponge Geodia japonica collected from the South China Sea, including two new isomalabaricane-type nortriterpenoids, geoditins A (1) and B (2), and a new sterol derivative (4). All chemical structures were established by interpretation of the spectroscopic data.
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| 11764864 |
Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections |
None |
Am Fam Physician |
Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections
Abstract
- The steady increase in resistant organisms is related to the widespread use of antibiotics in community and hospital settings. New therapeutic options are needed, including treatments for infections caused by antibiotic-resistant gram-positive organisms. Quinupristin-dalfopristin, the first formulation of a distinct class of antibiotics known as the streptogramins, has activity against a range of gram-positive bacteria that are usually resistant to other agents, including vancomycin-resistant Enterococcus faecium. The pharmacodynamic (postantibiotic effect) and pharmacokinetic characteristics of quinupristin-dalfopristin allow dosing at eight- to 12-hour intervals. The safety profile of the formulation is generally favorable, with no demonstrable ototoxicity, nephrotoxicity, bone marrow suppression, or cardiovascular adverse effects. Reversible arthralgias, myalgias, and peripheral venous irritation are the formulation's major side effects. A potential for drug interactions exists because quinupristin-dalfopristin significantly inhibits the cytochrome P450-3A4 enzyme system. Quinupristin-dalfopristin has been shown to be effective in the management of documented severe infections caused by vancomycin-resistant E. faecium, nosocomial pneumonia, and infections related to the use of intravascular catheters.
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| 11769252 |
The effects of a cyanobacterial crude extract on different aquatic organisms: evidence for cyanobacterial toxin modulating factors |
10.1002/tox.10014. |
Environ Toxicol |
The effects of a cyanobacterial crude extract on different aquatic organisms: evidence for cyanobacterial toxin modulating factors
Abstract
- In an aquatic ecosystem, during cyanobacterial bloom lysis, a mixture of toxins and other cyanobacterial and bacterial components will be present in the water, acting on aquatic organisms. Most of the research into toxic effects of cyanobacteria has involved the use of purified toxins. In this study, the "real-life" situation of a cyanobacterial lysis event was investigated. For this purpose, intact cells from a natural cyanobacterial bloom from Lake Müggelsee, Berlin, were taken and the cells were broken by repeated freeze/thaw cycles. This crude extract was used to expose several aquatic organisms ranging from microalgae (Scenedesmus armatus), macrophyte (Ceratophyllum demersum), invertebrate (Chaoborus crystallinus) up to fish eggs (Danio rerio) to look at several physiological parameters such as detoxication enzyme activity and, in the case of the microalgae and the macrophyte, also the effect on activity of photosynthesis. In all the tests, the cyanobacterial crude extract caused stronger effects than the pure cyanobacterial toxins used in equivalent concentrations.
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| 11780052 |
The DNA sequence and comparative analysis of human chromosome 20. |
10.1038/414865a |
Nature |
The DNA sequence and comparative analysis of human chromosome 20.
Abstract
- The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.
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| 11788572 |
Novel cationic trypsinogen (PRSS1) N29T and R122C mutations cause autosomal dominant hereditary pancreatitis |
10.1136/gut.50.2.271. |
Gut |
Novel cationic trypsinogen (PRSS1) N29T and R122C mutations cause autosomal dominant hereditary pancreatitis
Abstract
- Hereditary pancreatitis (HP) is usually caused by mutations in the cationic trypsinogen (PRSS1) gene, especially R122H or N29I. We sequenced the PRSS1 gene in the proband of families without these common mutations. Novel R122C and N29T mutations were detected in independent families that segregated with the disease in an autosomal dominant fashion. The R122C mutation eliminates the arginine autolysis site as with R122H mutations. The N29T mutation may also enhance intrapancreatic trypsin activity as has been demonstrated in vitro. Identification of these new mutations requires special attention as commonly used detection methods may fail.
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| 11804488 |
A convergent approach to cyclopeptide alkaloids: total synthesis of sanjoinine G1 |
10.1021/ja0170807. |
J Am Chem Soc |
A convergent approach to cyclopeptide alkaloids: total synthesis of sanjoinine G1
Abstract
- A general strategy for the synthesis of cyclopeptide alkaloids containing an endocyclic aryl-alkyl ether bond has been developed featuring a key intramolecular S(N)Ar reaction. The importance of the N-terminal protective group in the realization of such a strategy is documented. From the appropriate amino acid constituents, the natural sanjoinine G1, a 14-membered para cyclophane, has been synthesized in seven steps with 21% overall yield.
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| 11805094 |
X-ray crystallographic structures of the Escherichia coli periplasmic protein FhuD bound to hydroxamate-type siderophores and the antibiotic albomycin. |
10.1074/jbc.m109385200 |
J. Biol. Chem. |
X-ray crystallographic structures of the Escherichia coli periplasmic protein FhuD bound to hydroxamate-type siderophores and the antibiotic albomycin.
Abstract
- Siderophore-binding proteins play an essential role in the uptake of iron in many Gram-positive and Gram-negative bacteria. FhuD is an ATP-binding cassette-type (ABC-type) binding protein involved in the uptake of hydroxamate-type siderophores in Escherichia coli. Structures of FhuD complexed with the antibiotic albomycin, the fungal siderophore coprogen and the drug Desferal have been determined at high resolution by x-ray crystallography. FhuD has an unusual bilobal structure for a periplasmic ligand binding protein, with two mixed beta/alpha domains connected by a long alpha-helix. The binding site for hydroxamate-type ligands is composed of a shallow pocket that lies between these two domains. Recognition of siderophores primarily occurs through interactions between the iron-hydroxamate centers of each siderophore and the side chains of several key residues in the binding pocket. Rearrangements of side chains within the binding pocket accommodate the unique structural features of each siderophore. The backbones of the siderophores are not involved in any direct interactions with the protein, demonstrating how siderophores with considerable chemical and structural diversity can be bound by FhuD. For albomycin, which consists of an antibiotic group attached to a hydroxamate siderophore, electron density for the antibiotic portion was not observed. Therefore, this study provides a basis for the rational design of novel bacteriostatic agents, in the form of siderophore-antibiotic conjugates that can act as "Trojan horses," using the hydroxamate-type siderophore uptake system to actively deliver antibiotics directly into targeted pathogens.
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| 11807098 |
Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin (beta) subunits. |
10.1083/jcb.200103037 |
J. Cell Biol. |
Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin (beta) subunits.
Abstract
- Integrins connect the extracellular matrix with the cell interior, and transduce signals through interactions of their cytoplasmic tails with cytoskeletal and signaling proteins. Using the yeast two-hybrid system, we isolated a novel splice variant (filamin-Bvar-1) of the filamentous actin cross-linking protein, filamin-B, that interacts with the cytoplasmic domain of the integrin beta1A and beta1D subunits. RT-PCR analysis showed weak, but wide, expression of filamin-Bvar-1 and a similar splice variant of filamin-A (filamin-Avar-1) in human tissues. Furthermore, alternative splice variants of filamin-B and filamin-C, from which the flexible hinge-1 region is deleted (DeltaH1), were induced during in vitro differentiation of C2C12 mouse myoblasts. We show that both filamin-Avar-1 and filamin-Bvar-1 bind more strongly than their wild-type isoforms to different integrin beta subunits. The mere presence of the high-affinity binding site for beta1A is not sufficient for targeting the filamin-Bvar-1 construct to focal contacts. Interestingly, the simultaneous deletion of the H1 region is required for the localization of filamin-B at the tips of actin stress fibers. When expressed in C2C12 cells, filamin-Bvar-1(DeltaH1) accelerates their differentiation into myotubes. Furthermore, filamin-B variants lacking the H1 region induce the formation of thinner myotubes than those in cells containing variants with this region. These findings suggest that specific combinations of filamin mRNA splicing events modulate the organization of the actin cytoskeleton and the binding affinity for integrins.
|
| 11809060 |
Isolation and structure determination of obyanamide, a novel cytotoxic cyclic depsipeptide from the marine cyanobacterium Lyngbya confervoides |
10.1021/np0102253. |
J Nat Prod |
Isolation and structure determination of obyanamide, a novel cytotoxic cyclic depsipeptide from the marine cyanobacterium Lyngbya confervoides
Abstract
- Obyanamide (1) was isolated from a variety of the marine cyanobacterium Lyngbya confervoides collected in Saipan, Commonwealth of the Northern Mariana Islands. Gross structure elucidation of this novel cyclic depsipeptide relied on extensive application of 2D NMR techniques. The absolute stereochemistry was deduced by chiral chromatography of the hydrolysis products and comparison with authentic and synthetic standards. Obyanamide (1) was cytotoxic against KB cells with an IC(50) of 0.58 microg/mL.
|
| 11812144 |
Solution structure of Pisum sativum defensin 1 by high resolution NMR: plant defensins, identical backbone with different mechanisms of action |
10.1006/jmbi.2001.5252. |
J Mol Biol |
Solution structure of Pisum sativum defensin 1 by high resolution NMR: plant defensins, identical backbone with different mechanisms of action
Abstract
- Pisum sativum defensin 1 (Psd1) is a 46 amino acid residue plant defensin isolated from seeds of pea. The three-dimensional structure in solution of Psd1 was determined by two-dimensional NMR data recorded at 600 MHz. Experimental restraints were used for structure calculation using CNS and torsion-angle molecular dynamics. The 20 lowest energy structures were selected and further subjected to minimization, giving a root-mean-square deviation of 0.78(+/- 0.22) A in the backbone and 1.91(+/-0.60) A for over all atoms of the molecule. The protein has a globular fold with a triple-stranded antiparalell beta-sheet and an alpha-helix (from residue Asn17 to Leu27). Psd1 presents the so called "cysteine stabilized alpha/beta motif" and presents identical three-dimensional topology in the backbone with other defensins and neurotoxins. Comparison of the electrostatic surface potential among proteins with high three-dimensional (selected using the softwares TOP and DALI) topology gave insights into the mode of action of Psd1. The surface topologies between proteins that present antifungal activity or sodium channel inhibiting activity are different. On the other hand the surface topology presents several common features with potassium channel inhibitors, suggesting that Psd1 presents this activity. Other common features with potassium channel inhibitors were found including the presence of a lysine residue essential for inhibitory activity. The identity of Psd1 in primary sequence is not enough to infer a mechanism of action, in contrast with the strategy proposed here.
|
| 11827028 |
Isolation and structural determination of phepropeptins A, B, C, and D, new proteasome inhibitors, produced by Streptomyces sp |
10.7164/antibiotics.54.874. |
J Antibiot (Tokyo) |
Isolation and structural determination of phepropeptins A, B, C, and D, new proteasome inhibitors, produced by Streptomyces sp
Abstract
- We have isolated four related compounds named phepropeptins A, B, C, and D, as inhibitors of proteasome proposed to regulate many cellular functions. From an NMR analysis, the phepropeptins appeared as cyclic hexapeptides, differing in the two residues of the constituent amino acids from one another, with four conserved amino acid moieties. Based on an amino acid analysis, we synthesized two possible cyclic peptides to phepropeptin B that differ in the configurations. A comparison of the properties between the natural and synthesized compounds revealed that the structure of phepropeptin B was cyclo(-L-Leu-D-Phe-L-Pro-L-Phe-D-Leu-L-Val-). The phepropeptins showed inhibition to the proteasomal chymotrypsin-like activity but not to alpha-chymotrypsin.
|
| 11827484 |
Crystal structures of the SH2 domain of Grb2: highlight on the binding of a new high-affinity inhibitor |
10.1006/jmbi.2001.5299. |
J Mol Biol |
Crystal structures of the SH2 domain of Grb2: highlight on the binding of a new high-affinity inhibitor
Abstract
- The activation of growth factor receptors induces phosphorylation of tyrosine residues in its C-terminal part, creating binding sites for SH2 domain-containing proteins. Grb2 is a protein that recruits Sos, the exchange factor for Ras. Recruitment of Sos allows for Ras activation and subsequent signal transmission. This promotes translocation of MAP kinases into the nucleus and activation of early transcription factors. Grb2, a 25 kDa protein, is composed of one SH2 domain surrounded by two SH3 domains. The SH2 domain of Grb2 binds to class II phosphotyrosyl peptides with the consensus sequence pYXNX. Thus, Grb2 is a good example of a bifunctional adaptor protein that brings proteins into close proximity, allowing signal transduction through proteins located in different compartments. To explore the interactions between Grb2 and phosphorylated ligands, we have solved the crystal structure of complexes between the Grb2-SH2 domain and peptides corresponding to Shc-derived sequences. Two structures are described: the Grb2-SH2 domain in complex with PSpYVNVQN at 1.5 A; and the Grb2-SH2 domain in complex with mAZ*-pY-(alphaMe)pY-N-NH2 pseudo-peptide, at 2 A. Both are compared to an unliganded SH2 structure determined at 2.7 A which, interestingly enough, forms a dimer through two swapping subdomains from two symmetry-related molecules. The nanomolar affinity of the mAZ-pY-(alphaMe)pY-N-NH2 pseudo-peptide for Grb2-SH2 is related to new interactions with non- conserved residues. The design of Grb2-SH2 domain inhibitors that prevent interaction with tyrosine kinase proteins or other adaptors like Shc or IRS1 should provide a means to interrupt the Ras signaling pathway. Newly synthesized pseudo-peptides exhibit nanomolar affinities for the Grb2-SH2 domain. It will then be possible to design new inhibitors with similar affinity and simpler chemical structures.
|
| 11835990 |
Antimicrobial peptides with atypical structural features from the skin of the Japanese brown frog Rana japonica |
10.1016/s0196-9781(01)00634-9. |
Peptides |
Antimicrobial peptides with atypical structural features from the skin of the Japanese brown frog Rana japonica
Abstract
- Japonicin-1 (FFPIGVFCKIFKTC) and japonicin-2 (FGLPMLSILPKALCILLKRKC), two peptides with differential growth-inhibitory activity against the Gram-negative bacterium, Escherichia coli and the Gram-positive bacterium Staphylococcus aureus, were isolated from an extract of the skin of the Japanese brown frog Rana japonica. Both peptides show little amino acid sequence similarity to previously characterized antimicrobial peptides isolated from the skins of Ranid frogs. Circular dichroism studies, however, demonstrate that japonicin-2 adopts an alpha-helical conformation in 50% trifluoroethanol in common with many other cationic antimicrobial peptides synthesized in amphibian skin. Peptides belonging to the brevinin-1, brevinin-2, and tigerinin families, previously identified in the skins of Asian Ranid frogs, were not detected but a temporin-related peptide (ILPLVGNLLNDLL.NH(2); temporin-1Ja), that atypically bears no net positive charge, was isolated from the extract. The minimum inhibitory concentrations (MICs) of the peptides against E. coli were japonicin-1, 30 microM; japonicin-2, 12 microM; and temporin-1Ja > 100 microM. The MICs against S. aureus were japonicin-1, > 100 microM; japonicin-2, 20 microM; and temporin-1Ja, > 100 microM.
|
| 11836123 |
Psammaplin A, a chitinase inhibitor isolated from the Fijian marine sponge Aplysinella rhax |
10.1016/s0968-0896(01)00372-8. |
Bioorg Med Chem |
Psammaplin A, a chitinase inhibitor isolated from the Fijian marine sponge Aplysinella rhax
Abstract
- Several brominated tyrosine derived compounds, psammaplins A (1), K (2) and L (3) as well as bisaprasin (4) were isolated from the Fijian marine sponge Aplysinella rhax during a bioassay guided isolation protocol. Their structures were determined using NMR and MS techniques. Psammaplin A was found to moderately inhibit chitinase B from Serratia marcescens, the mode of inhibition being non-competitive. Crystallographic studies suggest that a disordered psammaplin A molecule is bound near the active site. Interestingly, psammaplin A was found to be a potent antifungal agent.
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