bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional characterization of the mammalian mRNA decapping enzyme hDcp2
Authors: PICCIRILLO CHRISTOPHER , KHANNA RICHIE , KILEDJIAN MEGERDITCH
Published: August 2003

Regulation of decapping is a critical determinant of mRNA stability. We recently identified hDcp2 as a human decapping enzyme with intrinsic decapping activity. This activity is specific to N7-methylated guanosine containing RNA. The hDcp2 enzyme does not function on the cap structure alone and is not sensitive to competition by cap analog, suggesting that hDcp2 requires the RNA for cap recognition. We now demonstrate that hDcp2 is an RNA-binding protein and its recognition and hydrolysis of the cap substrate is dependent on an initial interaction with the RNA moiety. A biochemical characterization of hDcp2 revealed that a 163 amino acid region containing two evolutionarily conserved regions, the Nudix fold hydrolase domain and the adjacent Box B region contained methyl-cap-specific hydrolysis activity. Maximum decapping activity for wild-type as well as truncation mutants of hDcp2 required Mn2+as a divalent cation. The demonstration that hDcp2 is an RNA-binding protein with an RNA-dependent decapping activity will now provide new approaches to identify specific mRNAs that are regulated by this decapping enzyme as well as provide novel avenues to control mRNA decapping and turnover by influencing the RNA-binding property of hDcp2.
Regulation of the vitamin B12 metabolism and transport in bacteria by a conserved RNA structural element
Authors: VITRESCHAK ALEXEY G. , RODIONOV DMITRY A. , MIRONOV ANDREY A. , GELFAND MIKHAIL S.
Published: August 2003

Cobalamin in the form of adenosylcobalamin (Ado-CBL) is known to repress expression of genes for vitamin B12 biosynthesis and be transported by a posttranscriptional regulatory mechanism, which involves direct binding of Ado-CBL to 5′untranslated gene regions (5′UTR). Using comparative analysis of genes and regulatory regions, we identified a highly conserved RNA structure, the B12-element, which is widely distributed in 5′UTRs of vitamin B12-related genes in eubacteria. Multiple alignment of approximately 200 B12-elements from 66 bacterial genomes reveals their common secondary structure and several extended regions of sequence conservation, including the previously known B12-box motif. In analogy to the model of regulation of the riboflavin and thiamin biosynthesis, we suggest Ado-CBL-mediated regulation based on formation of alternative RNA structures including the B12-element. In Gram-negative proteobacteria, as well as in cyanobacteria, actinobacteria, and the CFB group, the cobalamin biosynthesis and vitamin B12 transport genes are predicted to be regulated by inhibition of translation initiation, whereas in the Bacillus/Clostridium group of Gram-positive bacteria, these genes seem to be regulated by transcriptional antitermination. Phylogenetic analysis of the B12-elements reveals a large number of likely duplications of B12-elements in several bacterial genomes. These lineage-specific duplications of RNA regulatory elements seem to be a major evolutionary mechanism for expansion of the vitamin B12 regulon.
An endonuclease activity similar to Xenopus PMR1 catalyzes the degradation of normal and nonsense-containing human β-globin mRNA in erythroid cells
Authors: BREMER KIRSTEN A. , STEVENS AUDREY , SCHOENBERG DANIEL R.
Published: August 2003

β-globin mRNA bearing a nonsense codon is degraded in the cytoplasm of erythroid cells by endonuclease cleavage, preferentially at UG dinucleotides. An endonuclease activity in polysomes of MEL cells cleaved β-globin and albumin mRNA in vitro at many of the same sites as PMR1, an mRNA endonuclease purified from Xenopus liver. Stable transfection of MEL cells expressing normal human β-globin mRNA with a plasmid vector expressing the catalytically active form of PMR1 reduced the half-life of β-globin mRNA from 12 to 1–2 h without altering GAPDH mRNA decay. The reduced stability of β-globin mRNA in these cells was accompanied by an increase in the production of mRNA decay products corresponding to those seen in the degradation of nonsense-containing β-globin mRNA. Therefore, β-globin mRNA is cleaved in vivo by an endonuclease with properties similar to PMR1. Inhibiting translation with cycloheximide stabilized nonsense-containing β-globin mRNA, resulting in a fivefold increase in its steady-state level. Taken together, our results indicate that the surveillance of nonsense-containing β-globin mRNA in erythroid cells is a cytoplasmic process that functions on translating mRNA, and endonucleolytic cleavage constitutes one step in the process of β-globin mRNA decay.
Zeptomole detection of a viral nucleic acid using a target-activated ribozyme
Authors: VAISH NARENDRA K. , JADHAV VASANT R. , KOSSEN KARL , PASKO CHRISTOPHER , ANDREWS LORI E. , MCSWIGGEN JAMES A. , POLISKY BARRY , SEIWERT SCOTT D.
Published: August 2003

We describe a strategy for the ultra-sensitive detection of nucleic acids using “half” ribozymes that are devoid of catalytic activity unless completed by a trans-acting target nucleic acid. The half-ribozyme concept was initially demonstrated using a construct derived from a multiple turnover Class I ligase. Iterative RNA selection was carried out to evolve this half-ribozyme into one activated by a conserved sequence present in the hepatitis C virus (HCV) genome. Following sequence optimization of substrate RNAs, this HCV-activated half-ribozyme displayed a maximal turnover rate of 69 min−1 (pH 8.3) and was induced in rate by approximately 2.6 × 109-fold by the HCV target. It detected the HCV target oligonucleotide in the zeptomole range (6700 molecules), a sensitivity of detection roughly 2.6 × 106-fold greater than that previously demonstrated by oligonucleotide-activated ribozymes, and one that is sufficient for molecular diagnostic applications.
Mitochondrial RNase P RNAs in ascomycete fungi: Lineage-specific variations in RNA secondary structure
Authors: SEIF ELIAS R. , FORGET LISE , MARTIN NANCY C. , LANG B. FRANZ
Published: August 2003

The RNA subunit of mitochondrial RNase P (mtP-RNA) is encoded by a mitochondrial gene (rnpB) in several ascomycete fungi and in the protists Reclinomonas americana and Nephroselmis olivacea. By searching for universally conserved structural elements, we have identified previously unknown rnpB genes in the mitochondrial DNAs (mtDNAs) of two fission yeasts, Schizosaccharomyces pombe and Schizosaccharomyces octosporus; in the budding yeast Pichia canadensis; and in the archiascomycete Taphrina deformans. The expression of mtP-RNAs of the predicted size was experimentally confirmed in the two fission yeasts, and their precise 5′ and 3′ ends were determined by sequencing of cDNAs generated from circularized mtP-RNAs. Comparative RNA secondary structure modeling shows that in contrast to mtP-RNAs of the two protists R. americana and N. olivacea, those of ascomycete fungi all have highly reduced secondary structures. In certain budding yeasts, such as Saccharomycopsis fibuligera, we find only the two most conserved pairings, P1 and P4. A P18 pairing is conserved in Saccharomyces cerevisiae and its close relatives, whereas nearly half of the minimum bacterial consensus structure is retained in the RNAs of fission yeasts, Aspergillus nidulans and Taphrina deformans. The evolutionary implications of the reduction of mtP-RNA structures in ascomycetes will be discussed.
Delayed Onset of Oculogyric Crisis and Torticollis with Intramuscular Haloperidol
Authors: Jhee Stanford S , Zarotsky Victoria , Mohaupt Stephen M , Yones Cynthia L , Sims Steve J
Published: August 2003

Objective

To report a case of delayed-onset dystonic reactions, oculogyric crisis (OGC), and torticollis after treatment with intramuscular haloperidol lactate injection.

Case Summary

A 22-year-old Mexican American woman received intramuscular haloperidol lactate 7.5 mg followed 4 hours later by 10 mg. Twenty-six hours after the first injection, the patient reported that she was unable to lower her gaze and that her neck was stiff. She was immediately given intramuscular benztropine 2 mg; there was a nearly complete remission of symptoms within 15 minutes of treatment. An objective causality assessment revealed a probable relationship between the OGC/torticollis and haloperidol therapy.

Discussion

Dystonic reactions have been reported in 10–60% of patients treated with neuroleptic medication, most commonly when patients just start or increase the dose of the drug. The highest frequency of dystonic reactions has occurred in patients receiving high-potency neuroleptics. It has also been suggested that haloperidol-induced dystonic reactions are a result of the toxic metabolites of that agent.

Conclusions

OGC and torticollis reactions may occur 12–24 hours after treatment with a high-potency neuroleptic, even in the absence of symptoms of extrapyramidal side effects (EPSEs). The delayed dystonic reaction may begin suddenly (no early EPSE symptomatology).
Treatment of Hypertension in Bahrain
Authors: Khaja Khalid A Jassim Al , Sequeira Reginald P , Damanhori Awatif HH
Published: August 2003

Objective

To evaluate the adequacy of blood pressure (BP) control and therapeutic appropriateness of antihypertensive drug(s) prescribed, taking into consideration laboratory parameters and the presence of comorbidities, in hypertensive patients.

Methods

Therapeutic audit of medical records of hypertensive patients from 9 primary care health centers in Bahrain using World Health Organization/International Society of Hypertension guidelines criteria.

Results

The recommended target BP <140/<90 mm Hg was achieved in 37 (16.5%) patients with a mean BP of 126 ± 6 / 80 ± 5 mm Hg. Groups with inadequate BP control were 15 (6.7%) with normal systolic BP (SBP) and high diastolic BP (DBP), 59 (26.3%) with high SBP and normal DBP, and 113 (50.4%) with high SBP and high DBP. Pulse pressure of the controlled group was 46.3 ± 5.9, whereas pulse pressures of the inadequately controlled groups with BP cutoffs <140/≥90, ≥140/<90, and ≥140/≥90 mm Hg were 37.4 ± 6.1, 72.7 ± 13.5, and 59.7 ± 13.6 mm Hg, respectively. Of the 281 treated hypertensive patients, 56.6% were on monotherapy; BP of patients on combination therapy versus monotherapy did not differ. The choice of antihypertensives in relation to comorbidities and laboratory findings revealed that many hypertensive patients with dyslipidemia were on β-blockers and diuretics, 39.3% of patients with ischemic heart disease were on β-blockers, approximately 20% of patients with hyperuricemia were on diuretics, and 27.6% and 10.4% of patients with isolated systolic hypertension were on diuretics and calcium-channel blockers, respectively.

Conclusions

BP control was achieved in 1 of 6 treated patients. In several instances, metabolic abnormalities and comorbidities were apparently not considered while prescribing antihypertensives. A rational drug therapy approach is needed in treating hypertension to achieve better control rates.
Aspirin and Warfarin versus Aspirin Monotherapy after Myocardial Infarction
Authors: Jeddy Azzah S , Gleason Brenda L
Published: August 2003

Objective

To review data concerning combined aspirin/warfarin versus aspirin alone for secondary prevention after myocardial infarction (MI).

Data Sources

Literature was accessed through MEDLINE (1966–September 2002). Search terms included aspirin, warfarin, secondary prevention, and myocardial infarction.

Data Synthesis

Despite use of low-dose aspirin after an MI, risk of subsequent death and ischemic events remains high, making strategies for secondary prevention imperative. Relevant, large, long-term studies focusing on dual aspirin/warfarin versus aspirin alone in post-MI patients were evaluated.

Conclusions

Aspirin 75–325 mg/d should remain first-line therapy for secondary prevention after MI. Combining aspirin 75–81 mg with warfarin to maintain the international normalized ratio at 2.0–2.5 may provide added benefit, but should be considered only for patients at high risk for thromboembolic events.
Safety of COX-2 Inhibitors in Asthma Patients with Aspirin Hypersensitivity
Authors: West Patricia M , Fernández Cristina
Published: August 2003

Objective

To review the safety of cyclooxygenase-2 (COX-2) inhibitors in asthma patients with aspirin hypersensitivity.

Data Sources

Clinical studies were identified using MEDLINE (1966–September 2002). Key search terms included cyclooxygenase inhibitors, aspirin, asthma, and hypersensitivity. English-language articles were identified and included. References from the identified articles were also reviewed.

Data Synthesis

The literature provides information regarding the safety of COX-2 inhibitors in asthma patients with aspirin-exacerbated respiratory disease (AERD). The mechanism of AERD involves inhibition of cyclooxygenase, particularly COX-1. Inhibition of COX-1 causes an increased production of certain inflammatory mediators, which results in the reactions seen with AERD. Considering this mechanism, COX-2 inhibitors may be an alternative to aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) in a patient with AERD. This article analyzes 4 studies to evaluate the safety of COX-2 inhibitors in this population.

Results

The 4 studies evaluated included a total of 172 patients with AERD. All patients included demonstrated intolerance to aspirin or NSAIDs and tolerated the selective COX-2 inhibitor administered.

Conclusions

COX-2 inhibitors provide a potentially safe alternative for treatment of inflammatory conditions in patients with AERD.
Somnambulism Due to Probable Interaction of Valproic Acid and Zolpidem
Authors: Sattar S Pirzada , Ramaswamy Sriram , Bhatia Subhash C , Petty Frederick
Published: August 2003

Objective

To report a case of somnambulism due to a probable interaction between valproic acid and zolpidem in a patient with no prior personal or family history of somnambulism.

Case Summary

A 47-year-old white man with a history of bipolar disorder was being maintained on citalopram 40 mg once daily and zolpidem 5 mg at bedtime. During treatment, he developed manic symptoms and was started on adjunctive valproic acid therapy. Soon after this, he developed episodes of somnambulism, which stopped when valproic acid was discontinued. On rechallenge with valproic acid, somnambulism returned.

Discussion

To our knowledge, this is the first report in the literature describing a probable interaction between valproic acid and zolpidem leading to somnambulism. Even though valproic acid has been associated with sleep changes, there are no published reports of somnambulism with this agent. Zolpidem has been associated with somnambulism, but our patient did not experience this when he was on zolpidem monotherapy. However, within 2 days of starting adjunctive valproic acid, sleepwalking occurred. It stopped after valproic acid was withdrawn. On rechallenge with valproic acid, sleepwalking recurred. However, when zolpidem was discontinued and valproic acid was continued, somnambulism did not occur. An assessment on the Naranjo probability scale suggests probable pharmacokinetic or pharmacodynamic interactions between the 2 medications.

Conclusions

Valproic acid and zolpidem are generally safe medications that are commonly prescribed and often used together. No interactions have been previously reported with combined use of valproic acid and zolpidem. This case suggests a probable interaction between these 2 agents that can have a serious consequence, somnambulism. This could be frightening to patients and put them in danger. Recognition of such interactions that place patients at risk for potentially serious adverse events is imperative for appropriate care.
Oral Budesonide in the Management of Crohn's Disease
Authors: Hofer Kristi N
Published: August 2003

Objective

To review the pharmacology, pharmacokinetics, efficacy, and safety of oral budesonide (Entocort EC) in the treatment of mild to moderate Crohn's disease (CD).

Data Sources

The MEDLINE database (1966–December 2002) was searched using the key words budesonide and inflammatory bowel diseases and restricted to the English language. The references from relevant articles were also reviewed for additional citations.

Study Selection and Data Extraction

Articles and abstracts that evaluated oral budesonide for management of CD were considered, with emphasis on randomized, controlled clinical trials.

Data Synthesis

Budesonide's high potency at the glucocorticoid receptor and extensive first-pass hepatic metabolism result in a topical antiinflammatory effect on intestinal tissue, with minimal systemic glucocorticoid adverse effects. Clinical trials have demonstrated that budesonide is effective in the treatment of patients with mild to moderate CD of the ileum and ascending colon, with efficacy similar to prednisolone and superior to mesalamine. Long-term therapy with budesonide increased the duration of CD remission, but the effect was not sustained up to 1 year. Budesonide failed to prevent postsurgical relapse of CD. Adrenal suppression and glucocorticoid-related adverse effects have been reported at lower rates in patients treated with budesonide compared with prednisolone. Patients prescribed budesonide should be monitored for hepatic dysfunction and potential drug interactions.

Conclusions

Budesonide is an effective and relatively safe option for treatment of mild to moderate CD of the ileum and ascending colon.
2,6‐Diaryl‐4,4‐disubstituted 1,4‐dihydropyridines: Source for spiro heterocycles
Authors: Padmavathi V. , Balaiah A. , Reddy T. V. Ramana , Reddy B. Jagan Mohan , Reddy D. Bhaskar
Published: September 2003

Novel spiro heterocycles (5–12) were obtained by the cyclocondensation of 2,6‐diaryl‐4,4‐dimethoxycarbonyl‐/4‐cyano‐4‐ethoxycarbonyl‐1,4‐dihydropyridines(3/4) with hydrazine hydrate, hydroxylamine hydrochloride, urea, and thiourea. All the compounds were characterized by IR, 1H NMR, and 13C NMR spectral data.© 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:513–517, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10183
Aluminum five‐ and six‐coordination in bis(acetylacetonato)aminoalkoxides
Authors: Jain A. K. , Bohra R. , Mehrotra R. C. , Nagar S. , Sharma S.
Published: September 2003

Reactions of bis(acetylacetonato)aluminum(III)‐di‐μ‐isopropoxo‐di‐isopropoxo aluminum(III), [(CH3COCHCOCH3)2Al(μ‐OPri)2Al(OPri)2] with aminoalcohols, (HORNR1R2) in 1:1 and 1:2 molar ratios in refluxing anhydrous benzene yielded binuclear complexes of the types [(CH3COCHCOCH3)2Al(μ‐OPri)2Al(ORNR1R2)(OPri)] and [(CH3COCHCOCH3)2Al(μ‐OPri)2Al(ORNR1R2)2] (R  (CH2)3, R1 = R2 = H; R = CH2C(CH3)2, R1 = R2 = H; R = (CH2)2, R1 = H, R2 = CH3; and R  (CH2)2, R1 = R2 = CH3), respectively. All these compounds are soluble in common organic solvents and exhibit sharp melting points. Molecular weight determinations reveal their binuclear nature in refluxing benzene. Plausible structures have been proposed on the basis of elemental analysis, molecular weight measurements, IR, NMR (1H, 13C, and 27Al), and FAB mass spectral studies. 27Al NMR spectra show the presence of both five‐ and six‐coordinated aluminum sites. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:518–522, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10184
Thermolysis of symmetrical dithiobiurea and thioureidoethylthiourea derivatives
Authors: Hassan Alaa A. , Mourad Aboul‐Fetouh E. , El‐Shaieb Kamal M. , Abou‐Zied Ashraf H. , Döpp Dietrich
Published: September 2003

Microwave and thermal heterocyclization of N,N′‐disubstituted hydrazinecarbothioamide 1a,b and substituted thioureidoethylthioureas 2a–c as well as 1‐phenyl‐3[2‐(3‐phenylthio‐ureido)phenyl]thiourea 6 are reported. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:535–541, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10188
Synthesis of novel macrocyclic di‐ and tetralactams containing triazole subunits
Authors: Elwahy Ahmed H. M. , Abbas Ashraf A. , Kassab Refaie M.
Published: September 2003

The new macrocyclic di‐ and tetralactams 9, 15, and 16 were obtained in 16–24% yields by heating the appropriate bis‐amines 7 or 8 with the corresponding bisaldehyde 5 or 14 in refluxing acetic acid under high‐dilution conditions. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:551–559, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10191
Microwave‐assisted synthesis and diels–alder reactions of 1,3‐azaphospholo[5,1‐a]isoquinolines
Authors: Bansal Raj K. , Dandia Anshu , Gupta Nidhi , Jain Dheeraj
Published: September 2003

The application of microwave technique has been extended successfully for the first time to the synthesis of a representative class of azaphospholes, viz. 1,3‐bis(alkoxycarbonyl)‐1,3‐azaphospholo[5,1‐a]isoquinolines (2), which occurs rapidly giving higher yields. Stereoselectivity is observed in the reaction with 2,3‐dimethyl‐1,3‐butadiene, and isoprene reacts regioselectively as well. 1‐Methyl‐3‐ethoxycarbonyl‐1,3‐azaphospholo[1,5‐a]pyridine (4) remains inert toward [2+4] cycloaddition. The nonoccurrence of the Diels–Alder reaction in the latter case has been supported by semiempirical PM3 calculations. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:560–563, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10193
Stereospecific synthesis of azeto[2,1‐d]‐ [1,5]benzothiazepin/diazepin‐1‐ones
Authors: Huang Xu , Xu Jiaxi
Published: September 2003

2a,4‐Disubstituted 2‐phenoxy‐2,2a,3,4‐tetrahydro‐1H‐azeto[2,1‐d][1,5]benzothiazepin‐1‐ones and 5‐benzoyl‐2‐phenoxy‐2a,3,4,5‐tetrahydro‐azeto[1, 2‐a][1,5]benzodiazepin‐1(2H)‐ones were synthesized in moderate to good yields by stereospecific Staudinger cycloaddition reactions of 2,4‐disubstituted 2,3‐dihydro‐1,5‐benzothiazepines and 1‐benzoyl‐2,3‐dihydro‐1H‐1,5‐benzodiazepines, respectively, with phenoxy acetyl chloride in the presence of triethylamine in anhydrous benzene. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:564–569, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10196
Terpolymerization of ethyl methacrylate, N‐phenylmaleimide, and itaconic acid
Authors: Naguib Hala F. , Mokhtar Samia M. , Ali Raouf O. , Elsabeé Maher Z.
Published: September 2003

The terpolymerization of ethyl methacrylate (EMA), N‐phenylmaleimide (NPMI), and itaconic acid (IA) was investigated. The terpolymer composition was determined by elemental analysis and 1H NMR spectroscopy. The reactivity ratios of the three binary systems (EMA/NPMI, EMA/IA, and NPMI/IA) were calculated and used for the calculation of the terpolymer composition with the terminal model equations. A comparison between the experimental and theoretical compositions was made. The rate of the terpolymerization process was measured dilatometrically at two total monomer concentrations; this was done to establish the presence of intermolecular interactions between the investigated monomers. The thermal analysis of the obtained terpolymers was performed by thermogravimetric analysis. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3180–3187, 2003
Metallo‐supramolecular micelles: Studies by analytical ultracentrifugation and electron microscopy
Authors: Vogel Vitali , Gohy Jean‐François , Lohmeijer Bas G. G. , Van Den Broek Jacomina A. , Haase Winfried , Schubert Ulrich S. , Schubert Dieter
Published: September 2003

In aqueous solutions, amphiphilic block copolymers in which a polystyrene (PS) segment is connected to a poly(ethylene oxide) (PEO) block via a bis(2,2′:6′,2″‐ terpyridine ruthenium) complex can form micelles. Such micelles of the protomer type PS20‐[Ru]‐PEO70, according to the preparation procedure representing frozen micelles, were studied by sedimentation velocity and sedimentation equilibrium analysis in an analytical ultracentrifuge and by transmission electron microscopy, with different techniques applied for the sample preparation. The particles obtained were surprisingly multifarious in size. In ultracentrifugation experiments performed at relatively low salt concentrations, the distributions of the sedimentation coefficients20,wshowed a pronounced peak at 9.6 S and a broad, only partly separated second peak around 14 S. The molar mass of the particles at the peak was around 430,000 g/mol, corresponding to an aggregation number of approximately 85. The average hydrodynamic diameter of the particles in the peak fraction was approximately 13 nm. In electron micrographs of negatively stained samples, spheres of diameters between 10 and 25 nm were the most abundant particles, but larger ones with a wide size range were also visible. The latter particles apparently were composed of smaller ones. The data from both sedimentation analysis and electron microscopy showed that (1) the studied compound formed primary micelles of diameters around 20 nm and (2) the primary micelles had a tendency toward aggregation. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3159–3168, 2003
A novel role for proliferin‐2 in the ex vivo expansion of hematopoietic stem cells
Authors: Choong Meng Ling , Tan Amabel C.L , Luo Biao , Lodish Harvey F
Published: September 2003

A family of proliferin genes was discovered on a microarray analysis of hematopoiesis supportive stromal cell lines. Proliferin‐2 (PLF2) increased the frequency of long‐term culture‐initiating cells (LTC‐IC) from 1 in 340 to 1 in 256 of the primary hematopoietic stem cell (HSC)‐enriched bone marrow cells grown on MS5.1 feeder layer. A repeat using AFT024 feeder layer also showed a similar increase in LTC‐IC (from 1 in 386 cells to 1 in 260 cells). The clonogenic output of the LTC‐ICs was also increased significantly. The growth of various hematopoietic and stromal cell lines treated with PLF2 was found to increase by 4–27%, as measured by cell count and DNA synthesis assay. These findings open up the possibility of using PLF2 as a new member of the growth factor cocktails for the ex vivo expansion of HSC.
Diethyldithiocarbamate inhibits the catalytic activity of xanthine oxidase
Authors: Kober Thorsten , König Ilona , Weber Martina , Kojda Georg
Published: September 2003

We sought to determine the effects of the superoxide dismutase (SOD) inhibitor diethyldithiocarbamate (DETC) on vascular superoxide production. Rat aortic rings treated with DETC (10 mM) showed no change of superoxide generation (5 μM lucigenin). Likewise, DETC did not change the expression and activity of vascular soluble guanylyl cyclase, an enzyme known to be extremely sensitive to superoxide. In striking contrast, DETC completely inhibited the superoxide production induced by 6‐anilino‐5,8‐quinolinedione (LY83583) and abolished the catalytic activity of xanthine oxidase (XO). Thus, DETC inhibits vascular superoxide production by blocking oxidoreductase enzymes such as XO and those reducing LY83583 in rat aorta.
The propagation speeds of calcium action potentials are remarkably invariant
Authors: Jaffe Lionel F.
Published: September 2003

This paper critically compiles all published cases of established or putative calcium action potentials (or ultrafast calcium waves) where their speeds are known and are not limited by intercellular delays. The 127 cases include data from neurons or nerve nets within systems that range from cnidaria, ctenophores, molluscs, crustaceans, worms, echinoderms and tunicates up to mammalian brains; from muscle cells within organisms that range from Beröe, Cestum, moths, a crab, molluscs, a tunicate, frogs, chick embryos and turtles up to mammalian hearts; from epithelia in cnidaria and tunicates; even from a dinoflagellate and an insectivorous plant as well as reconstituted heart strands. They reveal a restriction to values of about 10–40 cm/sec at 20 degrees C and comparable restrictions at other temperatures. Moreover — unlike the speeds of sodium action potentials — the speeds of calcium ones are unrelated to cell diameter, at least over the available range of about 0.1 to 30 microns. Why do calcium action potentials have such fixed propagation speeds? Perhaps evolution has driven them to be the fastest waves of calcium influx which avoid subsurface poisoning.
Dynamic compartmentalization of the voltage‐gated sodium channels in axons
Authors: Garrido Juan José , Fernandes Fanny , Moussif Anissa , Fache Marie‐Pierre , Giraud Pierre , Dargent Bénédicte
Published: September 2003

One of the major physiological roles of the neuronal voltage‐gated sodium channel is to generate action potentials at the axon hillock/initial segment and to ensure propagation along myelinated or unmyelinated fibers to nerve terminal. These processes require a precise distribution of sodium channels accumulated at high density in discrete subdomains of the nerve membrane. In neurons, information relevant to ion channel trafficking and compartmentalization into sub‐domains of the plasma membrane is far from being elucidated. Besides, whereas information on dendritic targeting is beginning to emerge, less is known about the mechanisms leading to the polarized distribution of proteins in axon. To obtain a better understanding of how neurons selectively target sodium channels to discrete subdomains of the nerve, we addressed the question as to whether any of the large intracellular regions of Nav1.2 contain axonal sorting and/or clustering signals. We first obtained evidence showing that addition of the cytoplasmic carboxy‐terminal region of Nav1.2 restricted the distribution of a dendritic‐axonal reporter protein to axons of hippocampal neurons. The analysis of mutants revealed that a di‐leucine‐based motif mediates chimera compartmentalization in axons and its elimination in soma and dendrites by endocytosis. The analysis of the others generated chimeras showed that the determinant conferring sodium channel clustering at the axonal initial segment is contained within the cytoplasmic loop connecting domains II‐III of Nav1.2. Expression of a soluble Nav1.2 II‐III linker protein led to the disorganization of endogenous sodium channels. The motif was sufficient to redirect a somatodendritic potassium channel to the axonal initial segment, a process involving association with ankyrin G. Thus, it is conceivable that concerted action of the two determinants is required for sodium channel compartmentalization in axons.
Jumping the Hurdles of Mental Health Care Wearing Cement Shoes: Where Does the Inpatient Psychiatric Nurse Fit in?
Authors: Benson Will D. , Briscoe Leslie
Published: September 2003

Are inpatient psychiatric nurses stagnant in their practice? Delaney’s (2002) article on the topic might lead to the assumption that inpatient psychiatric nursing personnel have no foundation for practice. This article elaborates on the skills and knowledge that inpatient nurses have and the circumstances under which those skills are performed and knowledge applied. Although the ability to articulate a framework for practice varies, this is not equivalent to stagnation of practice or neglect of care. Based on their educational backgrounds, inpatient psychiatric nurses use various approaches and knowledge for care. Inpatient psychiatric nursing is relevant and dynamic.
Transpiration peak over a hill evergreen forest in northern Thailand in the late dry season: Assessing the seasonal changes in evapotranspiration using a multilayer model
Authors: Tanaka Katsunori , Takizawa Hideki , Tanaka Nobuaki , Kosaka Izumi , Yoshifuji Natsuko , Tantasirin Chatchai , Piman Sirithanya , Suzuki Masakazu , Tangtham Nipon
Published: September 2003

The seasonal changes in evapotranspiration over a hill evergreen forest in northern Thailand (18°48′N, 98°54′E), in the Asian monsoon region, were simulated using a multilayer model and the boundary conditions above the canopy. The simulation considered the uncertainty in the leaf area index (LAI) and physiological parameters for both photosynthesis and stomatal conductance models. The parameters were based on the estimated LAI and determined by referring to the measured net photosynthesis rate and stomatal conductance for a single leaf. The simulated cumulative evapotranspiration and rainfall interception agreed with the values obtained from the water budget within these uncertainties. The sensitivity of these limits to both evaporation and transpiration was also investigated. The simulated transpiration peaked in the late dry season. The latent heat flux obtained with the eddy correlation technique showed that the forest continued to transpire in the late dry season. The heat pulse velocities also showed a peak in water use by individual trees in the late dry season. These results counter the view that evapotranspiration declines in the dry season, as has been reported previously for an evergreen forest and other vegetation in Thailand. The transpiration peak was thought to depend on the reduced wetness of the canopy, and the consequent lack of evaporation from it, and on the fact that there was little decline in stomatal conductance, even in the driest conditions.
Inundation of a Dutch river polder, sensitivity analysis of a physically based inundation model using historic data
Authors: Hesselink Annika W. , Stelling Guus S. , Kwadijk Jaap C. J. , Middelkoop Hans
Published: September 2003

The inundation model Delft flooding system (Delft‐FLS) was applied to simulating the historical flood of 1805 in the polder Land van Maas en Waal (Netherlands). Delft‐FLS is a two‐dimensional (2‐D) hydrodynamic model that simulates overland flow. Sensitivity analyses show a large influence of floodplain topography and hydraulic friction on the propagation of the inundation. Because of the typical topography of Dutch polders, a virtually flat floodplain bordered by high dikes, the extent of the inundated area alone cannot be used for evaluating the model performance. Therefore the inundation time and water levels within the inundated area were used to test the model capabilities. This study shows that using historic data has a potential advantage over using contemporary data. Historic data allow evaluation of a model for real flood disasters that have long return periods and, fortunately, have not occurred in modern times.
The impact of the wind stress curl in the North Atlantic on the Atlantic inflow to the Norwegian Sea toward the Arctic
Authors: Orvik Kjell Arild , Skagseth Øystein
Published: September 2003

The Norwegian Atlantic Current (NwAC) through the Norwegian Sea serves as a conduit of warm and saline Atlantic water from the North Atlantic to the Arctic Ocean, an important factor for climate and ecology. In this study, we concentrate on how the North Atlantic wind stress curl (NAWSC) affects interannual variability on the major branch of the NwAC—the Norwegian Atlantic Slope Current (NwASC). Based on wind stress data from the NCEP reanalysis and estimated volume transport of the NwASC from current records during 1995–2003 in the Svinøy section (62°N), our analysis shows that the volume transport in the NwASC exhibits a maximum correlation of 0.88 with the zonally integrated NAWSC at 55°N 15 months earlier. Our findings reveal the NAWSC to be a major forcing for interannual variability of the NwASC in the range of 3.0‐ to 5.3 Sv (Sv = 106 m3 s−1). The 15 month time lag appears to be in accordance with a forced baroclinic Rossby wave in response to the local Ekman pumping changing the baroclinicity and strength of the North Atlantic Current (NAC). After being converted to a nearly barotropic shelf edge current along the Irish‐Scottish shelf through interaction with bottom topography, it appears as a barotropic response downstream in the Svinøy section. This result suggests the possibility of predicting conditions influenced by the NwASC more than a year in advance, using the NAWSC as a proxy.
Concomitant surgery with tension‐free vaginal tape
Authors: Huang Kuan‐Hui , Kung Fu‐Tsai , Liang Hsi‐Mi , Huang Li‐Ying , Chang Shiuh‐Young
Published: September 2003

Background.  To evaluate the efficacy and feasibility of tension‐free vaginal tape (TVT) surgery combined with gynecologic surgery using general anesthesia.

Methods.  One hundred and six women with genuine stress incontinence (GSI) diagnosed with a traditional urodynamic examination were prospectively enrolled into this study. All of the 106 women underwent TVT surgery for the treatment of GSI, along with a concomitant hysterectomy procedure, under general anesthesia. We estimated the severity of incontinence symptoms on a visual analog scale (VAS), and used a questionnaire for subjective assessment before and after TVT surgery. The objective assessment of urinary incontinence was carried out with a 1‐h pad test and traditional urodynamic examination. Of the 106 patients, 50 had uterine prolapse and underwent transvaginal hysterectomy and anteroposterior colporrhaphy (APC), and another 50 had uterine myoma and underwent laparoscopic‐assisted vaginal hysterectomy (LAVH).

Results.  The follow‐up mean interval was 18 months (range 12–36 months). The 50 women undergoing LAVH and TVT surgery had a mean hospitalization of 3.5 days. The subjective success rate was 90.5% and the objective success rate was 86.8%. The other group of 50 women undergoing vaginal total hysterectomy (VTH), APC and TVT surgery had a mean hospitalization of 4.8 days. The subjective success rate was 88.6% and the objective success rate was 84.9%. There were six patients lost to follow‐up for several reasons. The rates of complications of bladder perforation, postoperative voiding difficulty and postoperative urinary urgency were 2%, 11% and 10%, respectively; neither pelvic hematoma requiring blood transfusion nor conversion to laparotomy occurred.

Conclusion.  The results of this study prove that the TVT procedure, performed under general anesthesia without the need for the intraoperative cough provocation test to treat GSI, and carried out concomitantly with other gynecologic surgeries, is safe and effective.
Dynamics of bone tissue formation in tooth extraction sites
Authors: Cardaropoli G. , Araújo M. , Lindhe J.
Published: September 2003

Objectives: The aim of the present experiment was to study events involved in the healing of marginal, central and apical compartments of an extraction socket, from the formation of a blood clot, to bone tissue formation and remodeling of the newly formed hard tissue.

Material and Methods: Nine mongrel dogs were used for the experiment. The fourth mandibular premolars were selected for study and were divided into one mesial and one distal portion. The distal root was removed and the socket with surrounding soft and mineralized tissue was denoted “experimental unit”. The dogs were killed 1, 3, 7, 14, 30, 60, 90, 120 and 180 days after the root extractions. Biopsies including the experimental units were demineralized in EDTA, dehydrated in ethanol and embedded in paraffin. Serial sections 7 μm thick were cut in a mesio‐distal plane. From each biopsy, three sections representing the central part of the socket were selected for histological examination. Morphometric measurements were performed to determine the volume occupied by different types of tissues in the marginal, central and apical compartments of the extraction socket at different intervals.

Results: During the first 3 days of healing, a blood clot was found to occupy most of the extraction site. After seven days this clot was in part replaced with a provisional matrix (PCT). On day 14, the tissue of the socket was comprised of PM and woven bone. On day 30, mineralized bone occupied 88% of the socket volume. This tissue had decreased to 15% on day 180. The portion occupied by bone marrow(BM) in the day 60 specimens was about 75%, but had increased to 85% on day 180.

Conclusion: The healing of an extraction socket involved a series of events including the formation of a coagulum that was replaced by (i) a provisional connective tissue matrix, (ii) woven bone, and (iii) lamellar bone and BM. During the healing process a hard tissue bridge – cortical bone – formed, which “closed” the socket.
Inter‐relationships between rheumatoid arthritis and periodontal disease
Authors: Mercado F. B. , Marshall R. I. , Bartold P. M.
Published: September 2003

This review considers the considerable similarities between periodontal disease and rheumatoid arthritis (RA). While the etiology of these two diseases may differ, the underlying pathogenic mechanisms are remarkably similar and it is possible that individuals manifesting both periodontitis and RA may suffer from a unifying underlying systemic dysregulation of the inflammatory response. In light of these findings, the implications for the use of disease‐modifying medications in the management of these two chronic inflammatory conditions is apparent. Further longitudinal studies and medication‐based intervention studies are required to determine just how closely these two conditions are allied.
Locally delivered minocycline microspheres for the treatment of periodontitis in smokers
Authors: Paquette David , Oringer Richard , Lessem Jan , Offenbacher Steven , Genco Robert , Persson G. Rutger , Santucci Edward A. , Williams Ray C.
Published: September 2003

Aim: The aim of the present analysis of a larger phase 3 clinical trial was to evaluate the efficacy of 1 mg minocycline hydrochloride microencapsulated in 3 mg of resorbable polymer, subgingivally administered as an adjunct to scaling and root planing (SRP) in smokers with chronic periodontitis.

Material and Methods: Two hundred and seventy‐one patients who smoked were randomized to one of three treatment groups: (1) SRP alone, (2) SRP plus vehicle (polymer without minocycline) or (3) SRP plus minocycline microspheres. Full mouth SRP was performed for all groups at baseline, and vehicle or minocycline microspheres were administered to the appropriate patients at all periodontal pockets ≥5 mm at baseline, 3 and 6 months. Efficacy was evaluated over 9 months.

Results: Significantly greater pocket depth reductions with SRP plus adjunctive minocycline microsphere treatment were observed at 1, 6 and 9 months (p<0.05) versus control treatments. At 9 months, smokers treated with SRP plus minocycline microspheres exhibited a pocket depth reduction of 1.19 mm from baseline, as compared to 0.90 mm for smokers treated with SRP alone. The efficacy of adjunctive minocycline microspheres was consistent among all tested smoking subcohorts, including those based on gender, age and smoking exposures.

Conclusion: These data indicate that treatment with SRP plus locally delivered minocycline microspheres is more effective than SRP alone in reducing pocket depths in smokers with periodontitis.
Observations in classrooms using a network of handheld devices
Authors: Davis S.
Published: September 2003

Abstract This paper illustrates the educational implications of the design features of public anonymity and private accountability in a classroom network of handheld devices. The author draws from four years of observations of classes using two early network prototypes. Themes discussed are anonymity of data submission to the group, the ability for students to see their data displayed in the group space, the ability for the teacher to instantly assess how all students are doing at any time during a lesson, and that the ability of the network to let all students answer all questions may have an impact upon student engagement in the classroom. The paper goes on to highlight research done in the field of communications using synchronous electronic submission systems and relates this to the use of similar networks in the classroom.
Mobile learning in teacher training
Authors: Seppälä P. , Alamäki H.
Published: September 2003

Abstract  This paper describes a mobile learning project, where mobile devices are used for educational activities. The main focus of this paper is teacher training. Experiences on the use of mobile technology and how it was used in teacher training, especially how trainees and supervising teachers felt about it, are presented. The pilot study was carried out at the Department of Home Economics and Craft Science in University of Helsinki. The idea of the pilot was that the supervising teacher and trainee students could discus and share their ideas about teaching methods through the mobile device and use of a short message service (SMS) and digital pictures as a part of the supervising process. The use of digital pictures which were delivered via the mobile device proved to be surprisingly successful. The goal of these innovative pilot projects is to create flexible teaching solutions, which will enable access to information using different devices, and support learning in a variety of situations.
Niprisan (Nix‐0699) improves the survival rates of transgenic sickle cell mice under acute severe hypoxic conditions
Authors: Iyamu Efemwonkiekie W. , Turner Ernest A. , Asakura Toshio
Published: September 2003

Summary. The substitution of glutamic acid by valine at the sixth position of the beta‐globins of haemoglobin S (Hb S) causes a drastic reduction in the solubility of the deoxy form of Hb S. Under hypoxic conditions, deoxy‐Hb S molecules polymerize inside the cells, forming rigid, sickled cells. We studied the effect of Niprisan (Nix‐0699), a naturally occurring antisickling agent, on the survival of transgenic (Tg) sickle mice under severe acute hypoxic conditions (60 min). Before hypoxia exposure, the mice were treated by gavage once daily for 7 d with 0 mg/kg (n = 10), 10 mg/kg (n = 5), 50 mg/kg (n = 5), 300 mg/kg (n = 4) or 500 mg/kg (n = 5) of Nix‐0699. The mean survival times of the untreated and treated mice were 10, 25, 39, 55 or 60 min respectively. The percentage of sickled cells in the venous blood of the treated mice was lower than that in control mice and was dose dependent. Histological examination of the lungs of the control mice showed entrapment of massive numbers of sickled cells in the alveolar capillaries, although the degree of such entrapment decreased with the increased dose of Nix‐0699. Nix‐0699 may be a promising option for the treatment and management of patients with sickle cell disease.
Generation of a conditionally immortalized myeloid progenitor cell line requiring the presence of both interleukin‐3 and stem cell factor to survive and proliferate
Authors: Lee Candy , Evans Caroline A. , Spooncer Elaine , Pierce Andrew , Mottram Rachel , Whetton Anthony D.
Published: September 2003

Summary. The H‐2Κb temperature‐sensitive (ts) A58 transgenic (Immorto) mouse has been used previously to generate conditionally immortalized cells from a number of tissues. The present study aimed to investigate characteristics of primitive myeloid precursor cells derived from H‐2Κb‐tsA58 bone marrow. Cell populations were enriched for granulocyte/macrophage progenitors by centrifugal elutriation, and were cultured in the presence and absence of cytokines at the permissive and restrictive temperatures for the A58 oncogene. Cells derived from H‐2Κb‐tsA58 mice required both A58 activation and the growth factors, stem cell factor (SCF) and interleukin‐3 (IL‐3), for long‐term cell survival and growth; cells were maintained for > 300 d in culture under these conditions. IL‐3‐ and SCF‐dependent clonal cell lines were derived with a phenotype (lin–, Sca‐1+, CD34+, ER‐MP 58+, ER‐MP 12+, ER‐MP 20–) characteristic of primitive myeloid progenitors. These cells differentiated on addition of granulocyte/macrophage colony‐stimulating factor (GM‐CSF) or macrophage colony‐stimulating factor (M‐CSF) and acquired mature cell morphology with some upregulation of differentiation markers. In conclusion, the A58 oncogene can immortalize haemopoietic progenitor cells. These cells require two cytokines for growth, IL‐3 and SCF; as such, they constitute a useful resource for the study of synergistic interactions between growth factors. The ability to develop monocytic cell characteristics also permits the investigation of cytokine‐mediated early haemopoietic progenitor cell development.