A narrative meta-review of a series of systematic and meta-analytic reviews on the intervention outcome for children with developmental co-ordination disorder.

BACKGROUND: Systematic reviews and meta-analyses are considered to be the 'gold standards' for synthesizing research evidence in particular areas of enquiry. However, such reviews are only useful if they themselves are conducted to a sufficiently high standard. The aim of this study was to conduct a narrative meta-review of existing analyses of the effectiveness of interventions designed for children with developmental co-ordination disorder (DCD). METHODS: A narrative meta-review of systematic and meta-analytic reviews aimed at evaluating the effectiveness of intervention for children with DCD was conducted on studies published between 1950 and 2014. We identified suitable reviews, using a modification of the Population, Intervention, Comparison, Outcome (PICO) system and evaluated their methodological quality using the Assessment of Multiple Systematic Reviews (AMSTAR). In addition, the consistency of the quality of evidence and classification of intervention approaches was assessed independently by two assessors. RESULTS: The literature search yielded a total of four appropriate reviews published in the selected time span. The Assessment of Multiple Systematic Reviews percentage quality scores assigned to each review ranged from 0% (low quality) to 55% (medium quality). Evaluation of the quality of evidence and classification of intervention approaches yielded a discrepancy rate of 25%. All reviews concluded that some kind of intervention was better than none at all. CONCLUSIONS: Although the quality of the reviews progressively improved over the years, the shortcomings identified need to be addressed before concrete evidence regarding the best approach to intervention for children with DCD can be specified.

Coesite and stishovite in a shocked lunar meteorite, Asuka-881757, and impact events in lunar surface.

Microcrystals of coesite and stishovite were discovered as inclusions in amorphous silica grains in shocked melt pockets of a lunar meteorite Asuka-881757 by micro-Raman spectrometry, scanning electron microscopy, electron back-scatter diffraction, and transmission electron microscopy. These high-pressure polymorphs of SiO(2) in amorphous silica indicate that the meteorite experienced an equilibrium shock-pressure of at least 8-30 GPa. Secondary quartz grains are also observed in separate amorphous silica grains in the meteorite. The estimated age reported by the (39)Ar/(40)Ar chronology indicates that the source basalt of this meteorite was impacted at 3,800 Ma ago, time of lunar cataclysm; i.e., the heavy bombardment in the lunar surface. Observation of coesite and stishovite formed in the lunar breccias suggests that high-pressure impact metamorphism and formation of high-pressure minerals are common phenomena in brecciated lunar surface altered by the heavy meteoritic bombardment.

Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein.

We have isolated a novel actin filament-binding protein, named afadin, localized at cadherin-based cell-cell adherens junctions (AJs) in various tissues and cell lines. Afadin has one PDZ domain, three proline-rich regions, and one actin filament-binding domain. We found here that afadin directly interacted with a family of the immunoglobulin superfamily, which was isolated originally as the poliovirus receptor-related protein (PRR) family consisting of PRR1 and -2, and has been identified recently to be the alphaherpes virus receptor. PRR has a COOH-terminal consensus motif to which the PDZ domain of afadin binds. PRR and afadin were colocalized at cadherin-based cell-cell AJs in various tissues and cell lines. In E-cadherin-expressing EL cells, PRR was recruited to cadherin-based cell-cell AJs through interaction with afadin. PRR showed Ca2+-independent cell-cell adhesion activity. These results indicate that PRR is a cell-cell adhesion molecule of the immunoglobulin superfamily which is recruited to cadherin-based cell-cell AJs through interaction with afadin. We rename PRR as nectin (taken from the Latin word "necto" meaning "to connect").

Preparation and catalytic performances of ultralarge-pore TiSBA-15 mesoporous molecular sieves with very high Ti content.

Highly ordered TiSBA-15 mesoporous molecular sieves with different nSi/nTi ratios and tunable pore diameters have been prepared through direct synthesis under various hydrochloric acid concentrations and synthetic temperatures. The structure and the textural parameters of the materials were investigated by powder X-ray diffraction and nitrogen adsorption/desorption measurements. Decrease of the acid concentration and nSi/nTi ratio in the synthetic gel enhanced the amount of Ti incorporation in SBA-15 materials without affecting their structural order and textural parameters. Highly ordered mesoporous TiSBA-15 with a very high Ti content up to a nSi/nTi ratio of 1.9 was prepared for the first time under the optimized synthesis conditions. Control of synthetic temperature resulted in tuning of pore geometries without structural deterioration and Ti content. Ultralarge-pore TiSBA-15 with a pore size of 12.6 nm and a pore volume of 1.3 cm3 g-1 was also synthesized. The nature and the coordination of the Ti atoms in SBA-15 prepared under various synthesis conditions were investigated by UV-vis spectroscopy. It has been found that the Ti atoms are well-dispersed and mostly occupy the tetrahedral coordination under the optimized synthesis conditions. Catalytic performance of the obtained TiSBA-15 materials was also investigated through oxidation of styrene by hydrogen peroxide and tert-butylhydroperoxide as oxidants.

Different behavior of l-afadin and neurabin-II during the formation and destruction of cell-cell adherens junction.

We have recently isolated two novel actin filament-binding proteins, l-afadin and neurabin-II and shown that they are localized at cell-cell adherens junction (AJ) in epithelial cells. We found here that l-afadin, neurabin-II, ZO-1, and E-cadherin showed similar and different behavior during the formation and destruction of cell-cell AJ in MDCK cells. In MDCK cells, the accumulation of both l-afadin and E-cadherin, but not that of ZO-1, changed in parallel depending on Rac small G protein activity. Dissociation of MDCK cells by culturing the cells at 2 microM Ca2+ caused rapid endocytosis of E-cadherin, but not that of l-afadin or ZO-1. Addition of phorbol 12-myristate 13-acetate to these dissociated cells formed a tight junction-like structure where ZO-1 and l-afadin, but not neurabin-II or E-cadherin, accumulated. We furthermore found that, in non-epithelial EL cells, which expressed E-cadherin and attached to each other, l-afadin, neurabin-II, ZO-1 and E-cadherin were all localized at AJ. In cadherin-deficient L cells, I-afadin was mainly localized at cell-cell contact sites, but ZO-1 was mainly localized at the tip area of cell processes. Neurabin-II did not accumulate at the plasma membrane area. Neither l-afadin nor neurabin-II significantly interacted with alpha-, beta-catenin, E-cadherin, ZO-1 or occludin.

Two actions of frabin: direct activation of Cdc42 and indirect activation of Rac.

Frabin is an actin filament-binding protein which shows GDP/GTP exchange activity specific for Cdc42 small G protein and induces filopodium-like microspike formation and c-Jun N-terminal kinase (JNK) activation presumably through the activation of Cdc42. Frabin has one actin filament-binding (FAB) domain, one Dbl homology (DH) domain, first pleckstrin homology (PH) domain adjacent to the DH domain, one cysteine-rich FYVE domain, and second PH domain from the N-terminus to the C-terminus in this order. Different domains of frabin are involved in the microspike formation and the JNK activation, and the association of frabin with the actin cytoskeleton through the FAB domain is necessary for the microspike formation, but not for the JNK activation. We have found here that frabin induces the formation of not only filopodium-like microspikes but also lamellipodium-like structures in NIH3T3 and L fibroblasts. We have analysed the mechanism of frabin in these two actions and found that frabin induces filopodium-like microspike formation through the direct activation of Cdc42 and lamellipodium-like structure formation through the Cdc42-independent indirect activation of Rac small G protein. The FAB domain of frabin in addition to the DH domain and the first PH domain is necessary for the filopodium-like microspike formation, but not for the lamellipodium-like structure formation. The FYVE domain and the second PH domain in addition to the DH domain and the first PH domain are necessary for the lamellipodium-like structure formation. We show here these two actions of frabin in the regulation of cell morphology.

Swelling-induced O2- generation in guinea-pig neutrophils.

Without the addition of any exogenous stimuli, neutrophils generated O2- and then ceased in a reversible manner that correlated with cellular swelling and contraction. The nature of the possible mechanism responsible for this O2- generation was studied and compared with that observed in the triggering of stimulant-dependent O2- generation (respiratory burst). The swelling-induced O2- generation was inhibited by diphenyliodonium, and was independent of the functional distortion of mitochondrial and/or microsomal electron transport and xanthine oxidase. This suggested that such generation was involved in respiratory-burst oxidase activation; however, this generation was not accompanied by any new phosphorylation of the 47-kDa protein or of tyrosine proteins. Dihydrocytochalasin B potentiated the O2- generation. The cellular swelling produced a priming effect on the triggering of respiratory burst with different stimuli. Cellular contraction, conversely, suppressed the respiratory burst. The structural specificity of the swelling-induced plasma membrane modulation for the O2- generation was suggested by the finding that modulation of plasma membrane structures by various non-ionic detergents per se inhibited O2- generation. Lipophilic and positively-charged agents inhibited the generation and this inhibition was abrogated by negatively-charged, but not by non-ionic agents. Negatively-charged agents potentiated the O2- generation. These results suggest that both the interaction of the plasma membrane with the cytoskeleton and an increase in net negative charges at the plasma membrane play important role in evoking O2- generation; this is discussed and compared with the signal transduction reported previously for respiratory burst.

Charge-dependent regulation of NADPH oxidase activity in guinea-pig polymorphonuclear leukocytes.

The mechanism of respiratory burst was studied by modulating membrane surfaces with lipophilic ions in guinea-pig polymorphonuclear leukocytes and their subcellular membranes. Positively charged alkylamines in concentration ranges of 0.5 to 15 microM (ED50 values) inhibited the O2- generation with phorbol 12-myristate 13-acetate, N-formylmethionylleucylphenylalanine, A23187, myristate and arachidonate in intact cells, and the inhibition was relieved by negatively charged agents. A similar molecular size of alkylalcohols had no effects. A similar charge-dependent O2- generation was also observed with fatty acids in subcellular membrane fractions prepared from unstimulated control cells, and this was insensitive to H-7 and W-7. These results suggest that triggering of NADPH oxidase activation involves a reaction(s) that is regulated by membrane charges.

Selective interaction of D-beta-hydroxybutyrate dehydrogenase with intracellular membranes.

We are investigating the properties of pre-existing membrane structures that may contribute to localization of newly formed polypeptides on target membranes. To this end, D-beta-hydroxybutyrate dehydrogenase (EC 1.1.1.30) was purified from inner membranes of rat liver mitochondria and interacted with three different cellular membranes, as well as with liposomes prepared from membrane lipid extracts. (1) The purified lipid-free enzyme displayed little catalytic activity. Its activity was restored by interaction with rat liver mitochondrial inner membranes or microsomal membranes, but not with rat erythrocyte plasma membrane vesicles. (2) Plasma membranes from which membrane proteins had been partially removed did not reactivate the enzyme, but microsomal membranes treated in a similar manner displayed an increased efficiency of reactivation. (3) The selective reactivation found in the three membrane species was confirmed in liposomes prepared with total lipid extracts of the native membranes. The results suggest that the interaction of exogeneously added enzyme with the membranes is primarily dependent on lipid components or some specific lipid environment on the acceptor membranes.

Lipid-dependent interaction of D-beta-hydroxybutyrate dehydrogenase with cellular membranes.

A mechanism of selective localization of membrane-bound enzymes was examined by studying the interaction between D-beta-hydroxybutyrate dehydrogenase (EC 1.1.1.30) and native cellular membranes in which the lipid components were altered. (1) The catalytic activity of the purified lipid-free enzyme could be restored by the re-interaction with microsomal and mitochondrial membranes, whereas with erythrocyte membranes or liposomes from lipids of erythrocyte membranes this activity could not be restored (Miyahara, M., Utsumi, K. and Deamer, D.W. (1981) Biochim. Biophys. Acta 641, 222-231). In the erythrocyte lipid components, only lysophosphatidylcholine markedly inhibited the enzyme reactivation. (2) The inhibitory effect of lysophosphatidylcholine was confirmed in microsomes in which the lysophosphatidylcholine contents had been increased, by phospholipase A2 treatment, to the levels in erythrocyte membranes. (3) Selective digestion by phospholipase C of phosphatidylcholine in the microsomes was accompanied by a lowering of the level of reactivation in the membranes. (4) The presence of lipophilic alkyl compounds such as cetylamine and cetyltrimethylammonium bromide, which contain the ammonium group, in the membranes also inhibited the enzyme reactivation. However, negatively charged and neutral alkyl compounds were less suppressive. The results above suggested that the interaction of D-beta-hydroxybutyrate dehydrogenase with native cellular membranes is dependent on the amounts of phosphatidylcholine and lysophosphatidylcholine exposed on the membrane surface. It was also suggested that the presence of the ammonium group of non-diacyl compounds is unfavorable for the effective interaction of the enzyme.

Charge-dependent regulation of NADPH oxidase activities in intact and subcellular systems of polymorphonuclear leukocytes.

It has been reported that respiratory bursts with N-formylmethionylleucylphenylalanine, A23187, phorbol ester and fatty acids are switched off and on by modulating the net charges of plasma membranes in guinea-pig neutrophils (Miyahara, M. et al. (1987), Biochim. Biophys. Acta, 929, 253-262). In the present study, this was further extended in cells treated with protein kinase C inhibitors which completely suppressed the phorbol ester-dependent respiratory burst. This suggested that the initiation of the respiratory burst, which is generally accepted as linked to protein kinase C activation, might also be implicated in the net charge changes of plasma membranes. The above results were also supported by data obtained with a cell-free system reconstituted with plasma membranes and cytosolic fractions from unstimulated neutrophils, guanosine 5'-[gamma-thio]triphosphate and NADPH. Arachidonate stimulated NADPH oxidase activity accompanied by a marked phosphorylation of membrane proteins. The phosphorylation was sensitive to H-7, but it did not appear to be essential for the respiratory burst, because the oxidase activation was insensitive to H-7. Pretreating the plasma membranes with positively charged cetylamine inhibited the oxidase activation by arachidonate. These results suggest that a charge-dependent process, which does not use protein kinase C, may play an important role in the reaction leading to NADPH oxidase activation, and this may be related to the interaction of plasma membranes with the cytosolic activation factor.

Xenopus PKN: cloning and sequencing of the cDNA and identification of conserved domains.

cDNA clone encoding Xenopus laevis PKN has been isolated from Xenopus kidney library. Sequencing of this clone has revealed a single open reading frame encoding a protein of 901 amino acids. Immunoprecipitate from cytoplasmic fraction of COS7 cells transfected with this cDNA construct using antiserum against bacterially expressed Xenopus PKN revealed arachidonic acid-dependent autophosphorylation activity. Comparison of the closely related sequences of human and rat PKN with a protein from evolutionarily distant Xenopus, revealed several highly invariant domains in the NH2-terminal regulatory regions, suggesting that they participate in binding interaction with arachidonic acid.

Mitochondrial damage in galactosamine-induced liver intoxication in rats.

Mitochondria isolated from livers of rats which received D-galactosamine (375 mg/kg body wt., four times) demonstrated a marked decrease in respiratory control ratios, the ADP/O ratios, and state 3 respiration rates and an increase in state 4 respiration rates. The aberration was profound with site I being altered prior to sites II and III. Quantitation of phospholipids revealed a reduction of total phospholipids per mg protein with decreases in phosphatidylcholine and phosphatidylethanolamine contents. Caldiolipin was the only phospholipid which remained unaltered. Fatty acid composition was altered in these phospholipids; caldiolipin was altered most severely, showing reductions in linoleic and arachidonic acids, and an elevation in saturated fatty acids and in some other small components of fatty acids. In phosphatidylethanolamine, palmitic acid decreased, whereas stearic and docosahexenoic acids increased. These changes were smaller in phosphatidylcholine fatty acids. These mitochondria were also characterized by an altered composition in high molecular weight polypeptide components. By experiments with normal mitochondria in vitro, galactosamine, but not other aminohexoses, was proved to be an uncoupling agent of the oxidative phosphorylation system. Electron microscopic observation demonstrated that both in vivo and in vitro treatments with galactosamine induced marked disorganization of mitochondrial structures. These results suggest that mitochondrial damage is also included in galactosamine-induced hepatic lesion.

Characterization of the isoenzymes of cyclic nucleotide phosphodiesterase in human platelets and the effects of E4021.

In extracts of human platelets, three isoenzymes of cyclic nucleotide phosphodiesterase (PDE), namely, PDE2, PDE3, and PDE5, were identified; activities of PDE1 and PDE4 were not detected. In human platelets, the cGMP-hydrolytic activity was about six times higher than the cAMP-hydrolytic activity, and PDE5 and PDE3 are the major phosphodiesterase isoenzymes that hydrolyze cGMP and cAMP, respectively. PDE5 exhibited organ-specific expression in humans, and platelets were among the tissues richest in PDE5. A novel inhibitor of PDE5, sodium 1-[6-chloro-4-(3,4-methylenedioxybenzyl)aminoquinazolin-2-yl ] piperidine-4-carboxylate sesquihydrate (E4021), was a potent and highly selective inhibitor of human platelet PDE5. However, E4021 (up to 10 microM) did not inhibit 9,11-epithio-11,12-methano-thromboxane A2-induced platelet aggregation, in vitro. E4021 plus SIN-1 (3-morpholino-sydnonimine), at concentrations that had little effect individually, inhibited aggregation. These results suggest the unique distribution of phosphodiesterase isoenzymes in human platelets and the PDE5 inhibitors might be useful as a new class of antiplatelet drugs.

Effect of norepinephrine infusion on plasma vasopressin levels in normal human subjects.

Norepinephrine was continuously infused for 30 minutes at a rate of 0.2 and 0.3 mug/kg/min into 3 normal human subjects, and plasma vasopressin levels, plasma osmolality, hematocrit value, blood pressure, and heart rate were determined simultaneously. In norepinephrine infusion, an elevation of mean blood pressure and a decrease in heart rate was seen, and the degree of these changes was greater with the infusion at a rate of 0.3 mug/kg/min. Plasma vasopressin levels were suppressed by the infusion, and a dose-response relationship was recognized between the infusion at rates of 0.2 mug/kg/min and 0.3 mug/kg/min, while plasma osmolality did not change, and the hematocrit value rose slightly. These results suggest that norepinephrine-induced water diuresis is related to the suppression of the vasopressin release.

A study of plasma vasopressin in patients undergoing chronic hemodialysis.

Plasma vasopressin (VP) was determined in 28 patients with chronic renal failure undergoing hemodialysis. Plasma VP levels were significantly higher in the patients than in the normal subjects. It was also observed that plasma VP levels did not fall significantly despite a marked decrease of effective plasma osmolality following hemodialysis, and that no correlation was obtained between the plasma VP levels and effective plasma osmolality, both before and after hemodialysis. By analyzing the changes in blood volume and blood pressure in addition to plasma osmolality in each case, a dysfunction of VP release in response to osmotic stimulus was found in 5 out of 28 patients.

Permeability of antidiuretic hormone and other hormones through the dialysis membrane in patients undergoing chronic hemodialysis.

In eight patients undergoing chronic hemodialysis, ultrafiltration was performed for 1 h in each patient. The concentration of urea nitrogen, creatinine, ADH, cortisol, GH, prolactin and TSH was measured in plasma and the filtering solution, and the permeability of each substance was determined. The plasma concentration of ADH coincided with that of the filtering solution, and no significant difference was noted between the permeability of creating and ADH. In contrast, cortisol, GH, prolactin and TSH were not detected in the filtering solution. Chromatographic study showed that ADH in the filtering solution coincided with synthetic ADH. From a comparison of the permeability with the molecular weight, it was suggested that ADH in the blood exists in free form without binding with plasma proteins or neurophysin.

Isolation and characterization of the StyD4I restriction endonuclease, a neoschizomer of ScrFI, from Escherichia coli K-12 carrying a small multicopy Hsd plasmid of Salmonella typhi origin.

A restriction endonuclease, designated StyD4I, a neoschizomer of ScrFI, has been isolated from Escherichia coli K-12 carrying a small multicopy host specificity for DNA (Hsd) plasmid of Salmonella typhi D4 origin. In the presence of 10 mM Mg2+, StyD4I cleaves the sequence 5'-/CCNGG-3' and generates a 5-nucleotide cohesive end. StyD4I should be useful for recombinant DNA technology, because of the stability and ease in handling the producer cells.

Isolation and characterization of new restriction endonucleases from Vibrio parahaemolyticus: VpaK32I enzyme with the class-IIS heptanucleotide specificity, GCTCTTCN1/N4.

Six restriction endonucleases (ENases), classified into four different specificities, were found in a screen among 68 reference strains of Vibrio parahaemolyticus of human origin. Five of these ENases are isoschizomers of well-known ENases, while the remaining one, designated VpaK32I, is a novel and highly efficient class-IIS ENase with the hepatanucleotide recognition site, 5'-GCTCTTC(1/4)-3'.

Restriction endonuclease PshAI from Plesiomonas shigelloides with the novel recognition site 5'-GACNN/NNGTC.

A new restriction endonuclease (ENase), PshAI, has been isolated from Plesiomonas shigelloides 319-73, an organism that causes food poisoning in humans. The enzyme was stable and produced a yield of 410 units/g of cells. In the presence of 10 mM MgCl2, PshAI recognizes and cleaves the nucleotide sequence 5'-GACNN/NNGTC, producing blunt ends. PshAI will be useful for structural analysis and molecular cloning of DNA, because no ENases recognizing sequence GACNNNNGTC have been previously described.