bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced CD4 T cell activation and in vitro susceptibility to HIV-1 infection in exposed uninfected Central Africans
Authors: Bégaud Evélyne , Chartier Loïc , Marechal Valéry , Ipero Julienne , Léal Josianne , Versmisse Pierre , Breton Guillaume , Fontanet Arnaud , Capoulade-Metay Corinne , Fleury Hervé , Barré-Sinoussi Françoise , Scott-Algara Daniel , Pancino Gianfranco
Published: June 2006

Background

Environmentally driven immune activation was suggested to contribute to high rates of HIV-1 infection in Africa. We report here a study of immune activation markers and susceptibility to HIV-1 infection in vitro of forty-five highly exposed uninfected partners (EUs) of HIV-1 infected individuals in Central African Republic, in comparison with forty-four low-risk blood donors (UCs).

Results

Analysis of T lymphocyte subsets and activation markers in whole blood showed that the absolute values and the percentage of HLA-DR+CD4 T cells and of CCR5+CD4 T cells were lower in the EUs than in the UCs (p = 0.0001). Mutations in the CCR5 coding region were not found in either group. Susceptibility to in vitro infection of unstimulated peripheral blood mononuclear cells, prior of PHA activation, was decreased in EUs compared to UCs, either using a CXCR4-tropic or a CCR5-tropic HIV-1 strain (p = 0.02 and p = 0.05, respectively). Levels of MIP-1β, but not of MIP-1α or RANTES, in the supernatants of PHA-activated PBMC, were higher in the EUs than in the UCs (p = 0.007).

Conclusion

We found low levels of CD4 T cell activation and reduced PBMC susceptibility to HIV-1 infection in Central African EUs, indicating that both may contribute to the resistance to HIV-1 infection.
Robot-assisted reaching exercise promotes arm movement recovery in chronic hemiparetic stroke: a randomized controlled pilot study
Authors: Kahn Leonard E , Zygman Michele L , Rymer W Zev , Reinkensmeyer David J
Published: June 2006

Background and purpose

Providing active assistance to complete desired arm movements is a common technique in upper extremity rehabilitation after stroke. Such active assistance may improve recovery by affecting somatosensory input, motor planning, spasticity or soft tissue properties, but it is labor intensive and has not been validated in controlled trials. The purpose of this study was to investigate the effects of robotically administered active-assistive exercise and compare those with free reaching voluntary exercise in improving arm movement ability after chronic stroke.

Methods

Nineteen individuals at least one year post-stroke were randomized into one of two groups. One group performed 24 sessions of active-assistive reaching exercise with a simple robotic device, while a second group performed a task-matched amount of unassisted reaching. The main outcome measures were range and speed of supported arm movement, range, straightness and smoothness of unsupported reaching, and the Rancho Los Amigos Functional Test of Upper Extremity Function.

Results and discussion

There were significant improvements with training for range of motion and velocity of supported reaching, straightness of unsupported reaching, and functional movement ability. These improvements were not significantly different between the two training groups. The group that performed unassisted reaching exercise improved the smoothness of their reaching movements more than the robot-assisted group.

Conclusion

Improvements with both forms of exercise confirmed that repeated, task-related voluntary activation of the damaged motor system is a key stimulus to motor recovery following chronic stroke. Robotically assisting in reaching successfully improved arm movement ability, although it did not provide any detectable, additional value beyond the movement practice that occurred concurrently with it. The inability to detect any additional value of robot-assisted reaching may have been due to this pilot study's limited sample size, the specific diagnoses of the participants, or the inclusion of only individuals with chronic stroke.
Interferon treatment may trigger primary headaches in multiple sclerosis patients
Authors: Mantia L La , D’Amico D , Rigamonti A , Mascoli N , Bussone G , Milanese C
Published: June 2006

Recent data have suggested that interferon-b (IFN-β) may aggravate headaches in multiple sclerosis (MS) patients. The aim of this study was to investigate the life-time prevalence of primary headaches in MS patients treated with interferons in comparison with patients treated with other disease-modifying agents. Attention was focused on the onset of headache and the changes in pre-existing headaches in relation to the onset of therapy. The study was open-labelled and not randomized. We studied 150 consecutive MS patients treated with IFN-β (109 patients: 54 with 1b, 55 with 1a) and with other drugs (41 patients: 14 with glatiramer acetate, 27 with azathioprine). All patients underwent a semi-structured interview to diagnose headache type, according to the International Headache Society criteria. The frequency of primary headaches was higher in the interferon-group (72%) compared to patients in the other group (54%) ( P = 0.03). Worsening of pre-existing headaches or development of de novo headache occurred only in the interferon-group (41 and 48%, respectively) and not in the other group ( P<0.001). These results show that headache should be considered among the side-effects of interferon in MS patients.
A systematic review of oral methotrexate for multiple sclerosis
Authors: Gray O M , McDonnell G V , Forbes R B
Published: June 2006

Oral methotrexate is a potent immunosuppressant, which could have a beneficial effect on relapse rates and delay disease progression in multiple sclerosis (MS). We performed a systematic review of all randomized controlled trials of oral methotrexate for MS. Of the two randomized controlled trials identified, one was excluded due to its allocation concealment and definition of a relapse and time to sustained disease progression. The other trial studied 60 participants with progressive MS only. This trial reported a non-significant reduction in sustained Expanded Disability Status Scale (EDSS) progression and number of relapses in favour of methotrexate therapy. There were no data on relapse rate and no difference in time to first relapse. Minor side-effects were reported in both methotrexate (87.1%) and placebo groups (89.7%), but there were no major side-effects. Further trials are required in both relapsing-remitting and progressive groups to establish the role of oral methotrexate in MS.
Expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS white matter
Authors: Haddock G , Cross A K , Plumb J , Surr J , Buttle D J , Bunning R AD , Woodroofe M N
Published: June 2006

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) -1, -4 and -5 proteases have been identified in the CNS at the mRNA level. These glutamyl endopeptidases, inhibited by tissue inhibitor of metalloproteinases (TIMP)-3, are key enzymes in the degradation of the aggregating chondroitin sulphate proteoglycans (CSPGs), and may therefore play a role in CNS extracellular matrix (ECM) changes in multiple sclerosis (MS). We have investigated ADAMTS and TIMP-3 expression in normal and MS CNS white matter by real-time RT-PCR, western blotting and immunohistochemistry. We report for the first time the presence of ADAMTS-1, -4 and -5 in normal and MS white matter. Levels of ADAMTS-1 and -5 mRNA were decreased in MS compared to normal tissue, with no significant change in ADAMTS-4 mRNA levels. Protein levels of ADAMTS-4 were significantly higher in MS tissue compared to normal tissue. Immunohistochemical studies demonstrated that ADAMTS-4 was associated predominantly with astrocytes with increased expression within MS lesions. TIMP-3 mRNA was significantly decreased in MS compared to controls. These studies suggest a role for ADAMTS-4 in the pathogenesis of MS. Further studies on the activity of ADAMTS-4 will enable a better understanding of its role in the turnover of the ECM of white matter in MS.
Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis
Authors: Brass S D , Benedict R HB , Weinstock-Guttman B , Munschauer F , Bakshi R
Published: June 2006

Grey matter hypointensity on T2-weighted magnetic resonance imaging (MRI) scans, suggesting iron deposition, has been described in multiple sclerosis (MS) and is related to physical disability, disease course and brain atrophy. We tested the hypothesis that subcortical grey matter T2 hypointensity is related to cognitive impairment after adjusting for the effect of MRI lesion and atrophy measures. We studied 33 patients with MS and 14 healthy controls. Normalized T2 signal intensity in the caudate, putamen, globus pallidus and thalamus, total brain T1-hypointense lesion volume (T1LV), fluid-attenuated inversion-recovery-hyperintense lesion volume (FLLV) and brain parenchymal fraction (BPF) were obtained quantitatively. A neuropsychological composite score (NCS) encompassed new learning, attention, working memory, spatial processing and executive function. In each of the regions of interest, the normalized T2 intensity was lower in the MS versus control group (all P <0.001). Regression modelling tested the relative association between all MRI variables and NCS. Globus pallidus T2 hypointensity was the only variable selected in the final model ( R2 = 0.301, P = 0.007). Pearson correlations between MRI and NCS were T1LV: r = -0.319; FLLV: r = -0.347; BPF: r = 0.374; T2 hypointensity of the caudate: r = 0.305; globus pallidus: r = 0.395; putamen: r = 0.321; and thalamus: r = 0.265. Basal ganglia T2 hypointensity and BPF demonstrated the strongest associations with cognitive impairment on individual cognitive subtests. Subcortical grey matter T2 hypointensity is related to cognitive impairment in MS, supporting the clinical relevance of T2 hypointensity as a biological marker of MS tissue damage. These data implicate a role for basal ganglia iron deposition in neuropsychological dysfunction.
CD24 V/V is an allele associated with the risk of developing multiple sclerosis in the Spanish population
Authors: Otaegui D , Sáenz A , Camaño P , Blázquez L , Goicoechea M , Ruíz-Martínez J , Olaskoaga J , Emparanza J A , de Munain A López
Published: June 2006

The allele C in the CD24 gene has been related to multiple sclerosis (MS). In this work we check this single nucleotide polymorphism (SNP) in a population of 135 patients and 285 controls. Our results confirm the association between the V/V genotype at aa 57 of this gene and MS and highlight the importance of taking into account the origin of the subjects to avoid a population bias.
Periodic hyperthermia and abnormal circadian temperature rhythm in a patient with multiple sclerosis
Authors: Martinez-Rodriguez J E , Munteis E , Roquer J
Published: June 2006

Disturbances of the central thermoregulation in patients with multiple sclerosis (MS) are not often reported. We describe a 45-year old patient with a 13-year history of MS, who developed a clinical picture of recurrent hyperthermia. MRI showed a bilateral involvement of the hypothalamus in the setting of diffuse white matter disease. Serial body temperature measurement for five consecutive months disclosed an inversion of the circadian temperature rhythm. The clinical presentation and MRI findings suggested abnormalities of the central thermal control in relation to MS widespread involvement of the central nervous system (CNS).
Odd-skipped related 1 is required for development of the metanephric kidney and regulates formation and differentiation of kidney precursor cells
Authors: James Richard G. , Kamei Caramai N. , Wang Qingru , Jiang Rulang , Schultheiss Thomas M.
Published: June 2006

Formation of kidney tissue requires the generation of kidney precursor cells and their subsequent differentiation into nephrons, the functional filtration unit of the kidney. Here we report that the gene odd-skipped related 1 (Odd1) plays an important role in both these processes. Odd1 is the earliest known marker of the intermediate mesoderm, the precursor to all kidney tissue. It is localized to mesenchymal precursors within the mesonephric and metanephric kidney and is subsequently downregulated upon tubule differentiation. Mice lacking Odd1 do not form metanephric mesenchyme, and do not express several other factors required for metanephric kidney formation, including Eya1, Six2, Pax2, Sall1and Gdnf. In transient ectopic expression experiments in the chick embryo, Odd1 can promote expression of the mesonephric precursor markers Pax2 and Lim1. Finally, persistent expression of Odd1 in chick mesonephric precursor cells inhibits differentiation of these precursors into kidney tubules. These data indicate that Odd1plays an important role in establishing kidney precursor cells, and in regulating their differentiation into kidney tubular tissue.
Metastasis-associated kinase modulates Wnt signaling to regulate brain patterning and morphogenesis
Authors: Kibardin Alexey , Ossipova Olga , Sokol Sergei Y.
Published: June 2006

Wnt signaling is a major pathway regulating cell fate determination, cell proliferation and cell movements in vertebrate embryos. Distinct branches of this pathway activate β-catenin/TCF target genes and modulate morphogenetic movements in embryonic tissues by reorganizing the cytoskeleton. The selection of different molecular targets in the pathway is driven by multiple phosphorylation events. Here, we report that metastasis-associated kinase (MAK) is a novel regulator of Wnt signaling during morphogenetic movements, and eye and brain development in Xenopus embryos. Injected MAK RNA suppressed Wnt transcriptional reporters and activated Jun N-terminal kinase. Furthermore, MAK was recruited to the cell membrane by Frizzled 3,formed a complex with Dishevelled and phosphorylated Dsh in vitro. The regional brain markers Otx2, En2 and Gbx2 were affected in embryos with modulated MAK activity in a manner consistent with a role for MAK in midbrain-hindbrain boundary formation. Confirming the inhibitory role for this kinase in Wnt/β-catenin signaling, the midbrain patterning defects in embryos depleted of MAK were rescued by the simultaneous depletion ofβ-catenin. These findings indicate that MAK may function in different developmental processes as a switch between the canonical and non-canonical branches of Wnt signaling.
Dynamic redistribution ofvasahomolog and exclusion of somatic cell determinants during germ cell specification inCiona intestinalis
Authors: Shirae-Kurabayashi Maki , Nishikata Takahito , Takamura Katsumi , Tanaka Kimio J. , Nakamoto Chiaki , Nakamura Akira
Published: June 2006

Ascidian embryos sequester a specific cytoplasm, called the postplasm, at the posterior pole, where many maternal RNAs and proteins accumulate. Although the postplasm is thought to act as the germ plasm, it is also highly enriched in several factors essential for somatic cell development, and how the postplasm components regulate both germ and somatic cell differentiation remains elusive. Using a vasa homolog, CiVH, and other postplasmic components as markers, we found that the postplasm-containing blastomeres, the B7.6 cells, undergo an asymmetric cell division during gastrulation to produce two distinct daughter cells: B8.11 and B8.12. Most of the postplasmic components segregate only into the B8.11 cells, which never coalesce into the gonad. By contrast, the maternal CiVH RNA and protein are specifically distributed into the B8.12 cells, which divide further and are incorporated into the gonad in juveniles. In the B8.12 cells,CiVH production is upregulated from the maternal RNA source, resulting in the formation of perinuclear CiVH granules, which may be the nuage, a hallmark of germ cells in many animal species. We propose that the redistribution of specific maternal molecules into the B8.12 cells is essential for germ-cell specification in ascidians.
A WNTer wonderland in Snowbird
Authors: He Xi , Axelrod Jeffrey D.
Published: June 2006

The Keystone Symposium on `Wnt and β-catenin signaling in development and disease' was held recently in Snowbird, UT, USA. Organized by Mariann Bienz and Hans Clevers, this meeting covered a wide range of topics, including Wnt protein biogenesis, Wnt receptors and signaling pathways,β-catenin/Tcf complexes and gene expression, Wnt signaling in development, cancer, stem cell biology and regeneration, and therapeutics that target the Wnt/β-catenin pathway.
The murine homolog ofSALL4, a causative gene in Okihiro syndrome, is essential for embryonic stem cell proliferation, and cooperates withSall1in anorectal, heart, brain and kidney development
Authors: Sakaki-Yumoto Masayo , Kobayashi Chiyoko , Sato Akira , Fujimura Sayoko , Matsumoto Yuko , Takasato Minoru , Kodama Tatsuhiko , Aburatani Hiroyuki , Asashima Makoto , Yoshida Nobuaki , Nishinakamura Ryuichi
Published: June 2006

Mutations in SALL4, the human homolog of the Drosophilahomeotic gene spalt (sal), cause the autosomal dominant disorder known as Okihiro syndrome. In this study, we show that a targeted null mutation in the mouse Sall4 gene leads to lethality during peri-implantation. Growth of the inner cell mass from the knockout blastocysts was reduced, and Sall4-null embryonic stem (ES) cells proliferated poorly with no aberrant differentiation. Furthermore, we demonstrated that anorectal and heart anomalies in Okihiro syndrome are caused by Sall4haploinsufficiency and that Sall4/Sall1 heterozygotes exhibited an increased incidence of anorectal and heart anomalies, exencephaly and kidney agenesis. Sall4 and Sall1 formed heterodimers, and a truncated Sall1 caused mislocalization of Sall4 in the heterochromatin; thus, some symptoms of Townes-Brocks syndrome caused by SALL1 truncations could result from SALL4 inhibition.
The Structures and Bonding of Hyperlithiated Molecules
Authors: Kudo Hiroshi , Yokoyama Keiichi
Published: June 2006

This article describes the nature of bonding in hyperlithiated molecules with stoichiometries exceeding normal valence expectations. The existence of such hyperlithiated or hypervalent molecules as CLi6, Li3O, Li4O, Li5O, Li3S, Li4S, Li4P, Li2CN, Na2CN, and K2CN has already been experimentally confirmed by means of Knudsen-effusion mass spectrometry in our laboratory. These molecules have nine or more valence electrons, violating, at least formally, the octet rule. However, these molecules are thermodynamically more stable than the corresponding octet molecules. Results of ab initio MO calculations reveal that the extra valence electrons beyond the usual octet are in singly occupied orbitals (SOMO) or highest occupied orbitals (HOMO) in the LinA (A = C, O, P, S) molecules. The SOMO as well as HOMO forms the Li–Li bonds between all pairs of lithium atoms and contribute to stabilization of these molecules. The bonding situation of the M2CN (M = Li, Na, K) species is apparently different from that of LinA. The favored structure has Cs symmetry and is best described as a complex of the CN− anion with the M2+ cation. The extra valence electron is in SOMO, which corresponds to the radical cation SOMO and contributions to M–M bonding. The presence of the M2+ unit is a typical example of justifying the term hypervalent.
Structure of Concentrated Aqueous Sodium Formate Solutions
Authors: Kameda Yasuo , Mori Takahiro , Nishiyama Takashi , Usuki Takeshi , Uemura Osamu
Published: June 2006

Time-of-flight neutron and X-ray diffraction as well as Raman spectroscopic measurements were carried out on an aqueous 15 mol% HCOONa solution in order to investigate the hydration structure of both the formate and sodium ions in the concentrated aqueous solution. The intramolecular bond distances of DCOO− (rCD = 1.07 ± 0.01 Å, rCO = 1.272 ± 0.007 Å and rOO = 2.18 ± 0.02 Å) were determined through a least-squares fit of the observed neutron interference term in the high-Q region. The average hydrogen-bond distances between the D2O molecules in the solution (r(O···D) = 1.92 ± 0.02 Å and r(D···D) = 2.42 ± 0.02 Å) were also obtained. The hydration parameters on the formate ion were estimated to be rOformate···H2O = 2.82 ± 0.01 Å and nOformate···H2O = 4.4 ± 0.2 from a least-squares fit of the X-ray intermolecular interference term. A preferred orientation between the formate ion and hydrated water molecules was suggested from the present X-ray data. The hydration number of Na+ in the solution was given to be 4.6 ± 0.2, besides the intermolecular distance (rNa+···H2O = 2.37 ± 0.01 Å). The symmetrical stretching vibrational band of the hydrated sodium ion, Na+(H2O)n, in a 15 mol% HCOONa solution was observed at 225 cm−1 in the present isotropic Raman spectrum.
Kinetics and Mechanism of the Oxidation of Hydrogen Peroxide by Gold(III) in an Aqueous Hydrochloric Acid Medium
Authors: Sen Pratik K , Sanyal Ankan , Sen Gupta Kalyan K
Published: June 2006

The kinetics of the reaction between hydrogen peroxide and gold(III) in a hydrochloric acid medium has been studied. The reaction is first order with respect to [AuIII] as well as [H2O2]. The reaction rate has an inverse dependence on [H+] and [Cl−]. AuCl4−, AuCl3(OH2), and AuCl3(OH)− are the reactive species of Au(III). A rate expression consistent with the experimental findings has been proposed.
Potentiometric Response Properties of Sensor Membranes Based on Cobalt Phthalocyanine Conjugate-Polymer in Nonaqueous Solutions
Authors: Nakamura Toshio , Hayashi Chiharu , Ogawara Tetsushi
Published: June 2006

Some experiments are carried out in order to clarify the reason why the electrode prepared by coating a platinum disk with a non-plasticized membrane of polyacrylaminde polymer (PAA) coupled to cobalt phthalocyanine (CoPc) shows such a Nernstian response and a special selectivity for fluoride and cyanide ions in acetonitrile (AN). Special interactions between the ions and CoPc are observed spectrophotometrically. A complexing ability of the CoPc with only fluoride and cyanide ions works to respond in a Nernstian way for the ions at the electrode. Since the electrode shows quite poor response to chloride and bromide ions it can be understood that an ion exchange reaction of the ions in the solution at CoPc does not function to the response of the electrode. Furthermore, the PAA matrix of the membrane is found to produce the electrochemical masking effect on chloride and bromide ions. The PAA–CoPc electrode is confirmed as available for use of determining the solubility product constant of sodium fluoride in AN.
Study on the Conformation of an Isopropyl-Substituted Furylfulgide. Photochromic Coloring Reaction and Thermal Racemization
Authors: Yokoyama Yayoi , Ogawa Keiichiro , Iwai Takeshi , Shimazaki Kazuko , Kajihara Yasuhiro , Goto Takakazu , Yokoyama Yasushi , Kurita Yukio
Published: June 2006

The conformations of the E-forms of photochromic furylfulgides with a methyl substituent (1E) and an isopropyl substituent (2E) were investigated by X-ray crystallographic analyses, NMR measurements, and molecular orbital (MO) calculations in relation to the large quantum yield of the coloring reaction of 2E upon the irradiation of UV light. The conformations of 1E and 2E obtained by X-ray crystallographic analyses are the photocyclization-possible ones (Eα), in which the distances of the bond-forming carbon atoms of 1E and 2E are essentially the same. NOESY of 1H NMR measurements of 1E and 2E showed that they take both the Eα and cyclization-impossible Eβ conformations in solution. Although MO calculations of 2E proved that the population of 2Eα is dominant when the entropy contributions of the rotation of substituents are considered, the large difference in the quantum yields was not fully elucidated. The difference may have come from a difference in the nature of the excited states of 1E and 2E, which is evidenced by the large difference in the molar absorption coefficient (1E: 6700, 2E: 4250 mol−1 dm3 cm−1 in toluene).

The thermodynamic parameters of the enantiotopomerization process of 2E were determined by variable-temperature 1H NMR measurements. The mechanism of enantiotopomerization was specified by MO calculations.
Influence of Calcium Ions on the Mechanism of Oxime Formation from Acetoin
Authors: Fett Roseane , Brighente Inês Maria Costa , Yunes Rosendo Augusto
Published: June 2006

The effect of calcium ions on the reaction of acetoin with hydroxylamine was studied. This reaction proceeds by a two-step mechanism: the attack of hydroxylamine on the carbonyl compound to give a tetrahedral addition intermediate, and the dehydration of this intermediate to form the oxime. The presence of calcium ions decreases the value of the equilibrium constant of the tetrahedral addition intermediate formation, but increases the overall rate constant of the reaction when dehydration is the rate-determining step. Evidence suggests that the effect of calcium ions is through the formation of a complex with the hydroxyl groups of the tetrahedral addition intermediate, facilitating the dehydration step of the reaction.
Synthesis and Properties of Fluoroazulenes. II. Electrophilic Fluorination of Azulenes with N-Fluoro Reagents
Authors: Ueno Tetsuya , Toda Haruhiko , Yasunami Masafumi , Yoshifuji Masaaki
Published: June 2006

1-Fluoro- and 1,3-difluoroazulenes were synthesized for the first time by the electrophilic fluorination of azulenes with N-fluoro reagents. Selective preparation of 1-fluoroazulenes were performed by the fluorination of methyl azulene-1-carboxylates, followed by demethoxycarbonylation in 100% H3PO4. 2-Substituted azulenes were fluorinated in higher yields. In the 1H NMR of 1-fluoroazulene, long-range JFH values were not observed at H-2 and H-8, in contrast to those for 1-fluoronaphthalene. The 1-fluorine atom causes significant bathochromic shifts in the visible absorption of azulene, due to the so-called +Iπ effect.
Facilitated Photoreduction of Ruthenium Bis(4′-methylterpyridine) Pendant Myoglobin
Authors: Hamachi Itaru , Matsugi Tomoaki , Tanaka Shigeaki , Shinkai Seiji
Published: June 2006

A synthetic heme bearing ruthenium bis(terpyridine) through a covalent bond was successfully prepared. Ruthenium bis(terpyridine) pendant myoglobin, which was synthesized by a conventional cofactor reconstitution method, was efficiently activated through a photoinduced electron-transfer reaction from the ruthenium complex to the heme center. No reaction occurred in the corresponding intermolecular reaction system.
Conformational Preference in β-Aryldehydroalanine. Synthesis and Conformational Study of Tripeptides Containing β-Aryldehydroalanine Residues
Authors: Inai Yoshihito , Kurashima Shyu , Okado Yoshio , Hirabayashi Tadamichi , Yokota Kenji
Published: June 2006

In order to investigate the effect of bulky β-substituents on the conformational preference in α, β-dehydroamino acid residues, three kinds of tripeptides containing (Z)-β-phenyldehydroalanine, (Z)-β-(1-naphthyl)dehydroalanine, or (Z)-β-(1-pyrenyl)dehydroalanine residue were synthesized: Boc–Ala–ΔZAA–Val–OMe (Boc, t-butoxycarbonyl; Ala, L-alanine; ΔZAA, (Z)-β-aryldehydroalanine; Val, L-valine; OMe, methoxy). Their conformations in solution were investigated using 1H NMR spectroscopy. The solvent accessibility of the NH resonances and the nuclear Overhauser effect (NOE) indicated that the three peptides in CDCl3 form a type II β-turn conformation supported by hydrogen bonding between CO (Boc) and NH (Val). From a conformational energy calculation, the three kinds of ΔZAA residues were also shown to favor a type II β-turn conformation. In each β-turn, the orientation of the aryl plane was found to be non planar relative to the Cα=Cβ–Cγ plane, suggesting that a steric interaction between the β-aryl group and the peptide backbone leads to the internal rotation angles preferred for the β-turn backbone.
Comparison of the Efficiencies of the Fused Heterocyclic Compounds, 9H-Xanthene-2,7-diols, and Related Chain-Breaking Phenolic Antioxidants
Authors: Yamamura Tatsuo , Ishida Takafumi , Ueyama Hiroyuki , Hayashida Hirokazu , Ishimaru Takuya , Nishiyama Tomihiro
Published: June 2006

The antioxidant activities of 9H-xanthene-2,7-diols that are structurally related to tocopherols and 2,2′-alkylidenedi(hydroquinones) were measured by the inhibition of the thermally initiated autoxidation of tetralin at 60 °C using an oxygen-absorption method. The stoichiometric factors were calculated as n = 3.3—5.5 for 9H-xanthene-2,7-diols and 0.5—0.9 for 2,2′-alkylidenedi(hydroquinones) that lack the fused six-membered heterocyclic ring. Comparison of the alkyl substituent on the bridged methylene carbon showed that 9-methyl-9H-xanthene-2,7-diols increased in n value compared with 9-ethyl-9H-xanthene-2,7-diols. For the 9-methyl-9H-xanthene-2,7-diols, alkyl groups ortho to the phenolic hydroxyl group decreased the Rinh value: two methyl groups by 10-fold, one methyl group by 1.9-fold, and one t-butyl group by 1.4-fold, compared to that for the 9-methyl-9H-xanthene-2,7-diol. On the other hand, 2,2′-alkylidenedi(hydroquinones) were poorer antioxidants than the structurally comparable 9H-xanthene-2,7-diols. The low reactivity of 2,2′-alkylidenedi(hydroquinones) compared to those of 9H-xanthene-2,7-diols is attributed to electronic factors. The p-type lone pair on the hydroxyl oxygen can not help stabilizing the phenoxyl formed upon abstraction of the phenolic hydrogen.
Crystal Structure and Stereoselective Solid-State Photodimerization of 1-(9-Anthryl)alkyl Acetates
Authors: Mori Yukie , Horikoshi Yumiko , Maeda Koko
Published: June 2006

X-Ray structure analyses of 1-(9-anthryl)alkyl acetates [AnCH(OAc)R; An = 9-anthryl, R = Me (1a), Et (1b), i-Pr (1c), t-Bu (1d), CF3 (1e)] indicated that these molecules adopted similar conformations in which the bond connecting the chiral carbon and the substituent was oriented almost perpendicular to the anthracene plane. In the crystals of 1b—1e two adjacent anthracenes related by an inversion center was stacked with a short interplane distance (3.5—3.6 Å), which was favorable for the formation of the meso head-to-tail dimer. Photolysis of crystals of 1b, 1c, and 1e afforded meso-dimers in almost 100% yield, while 1d was photostable. The quantum yield of dimerization for 1b (0.16) was higher than that in solution. Although the dimerization did not proceed in single crystal-to-single crystal fashion, the observed high selectivity suggested that the reaction took place between the π-stacking pair even when the crystalline lattice of the monomer was destroyed. Irradiation of 1a—1e in benzene solution gave meso- and dl-head-to-tail dimers in a ratio of 1 : 1. The quantum yield of dimerization decreased with increase in the size of the substituent.
Synthesis and Properties of A–B–A Block Copoly(ester-ethers) Comprising Poly(l-lactide) (A) and Poly(oxypropylene-co-oxyethylene) (B) with Different Molecular Weights
Authors: Lee Chan Woo , Kimura Yoshiharu
Published: June 2006

An A–B–A triblock copoly(ester-ether) comprising poly(l-lactide) (A) and poly(oxyethylene-co-oxypropylene) (B) was prepared by copolymerization of l-lactide and a commercially available telechelic copolyether, Pluronic® (PN), with different molecular weights by the catalysis of tin(II) octanoate. The low molecular weight PN gave the copolymers having a low or medium molecular weight and a unit composition slightly different from the feed ratio. With PN whose molecular weight was around 10000, high molecular weight copolymers were obtained in high yield. For the PN with molecular weight of 8400, the block copolymerization was examined at different feed ratios, in which the molecular weight and the unit composition were successfully controlled by changing the l-lactide/PN ratio in feed. The copolymer containing 10 wt% of this PN was melt-spun into a filament, which was drawn to various draw ratios at 40 and 60 °C. The tensile modulus and strength of the filament increased with the draw ratio increasing at 60 °C, while at 40 °C they reached a plateau above the draw ratio of 5.0. It was found that the copolymer filaments showed an improved flexibility due to the incorporation of the soft PN segments. The in vitro hydrolysis test of the drawn filaments showed that the block copolymer has much higher degradability than the homo poly-l-lactide.
Audit of hepatitis C antibody requests made by a genito-urinary department
Authors: Williams P M , Edwards A
Published: June 2006

Requests for hepatitis C antibodies (HCV Ab) made by the Oxford Department of Genito-urinary (GU) Medicine were audited against national guidelines to determine how the service performed and to develop locally applicable standards. This resulted in more effective screening and cost savings.
Therapeutic immunization for the control of HIV-1: where are we now?
Authors: Dorrell Lucy
Published: June 2006

Highly active antiretroviral therapy (HAART) has transformed HIV-1 infection from an invariably fatal disease into a chronic infection requiring lifelong treatment. However, the challenges we still face are the urgent need to provide affordable sustainable therapy to the millions of infected individuals who live in resource-poor countries, and the limitations posed by serious drug toxicity and viral resistance associated with long-term therapy. Augmentation of HIV-specific immunity by therapeutic vaccination is a possible alternative to continuous HAART. In this review, progress in the development of therapeutic immunization strategies is discussed.
Medicolegal implications of Peyronie's disease: imprisonment or acquittal
Authors: Mohanty Kailash C
Published: June 2006

The presence of Peyronie's disease can serve as a potential defence against an accusation of rape. However, it can also facilitate an act of sexual intercourse establishing commission of a rape where it does not act as a defence. We describe two cases of Peyronie's disease where two defendants charged with rape pleaded not guilty on the ground of the presence of Peyronie's disease and they argued that they could not have committed the acts because of the severe bending of the penis. One of them was acquitted, whereas the other was found guilty and was imprisoned for six years for the offence of rape. The reason for the difference is development of the condition at a particular site in the penis with different implications. In one defendant, the fibrosis developed at the ventral site producing a curvature downwards, and in the other the fibrosis developed in the dorsal aspect producing a curvature upwards, which facilitated penile penetration.
Chlamydia trachomatis in cervical and vaginal swabs and urine specimens from women undergoing termination of pregnancy
Authors: Renton A , Thomas B M , Gill S , Lowndes C , Taylor-Robinson D , Patterson K
Published: June 2006

The study was devised to assess the prevalence of Chlamydia trachomatis in endocervical and vaginal swabs and first pass urine specimens from women presenting for termination of pregnancy (TOP) and to evaluate the performance of the tests used, namely the ligase chain reaction (LCR) and the direct fluorescence antibody (DFA) test. Eight hundred and sixty three (91%) of 948 women invited to participate agreed to do so; a complete set of results for all test-site combinations was achieved for 793 (92%). The overall prevalence of C. trachomatis was 8.54% (95% confidence interval [CI]: 7.6–10.5%) with a significant negative association with age. The sensitivity (95% CI) of the LCR test for cervical, vaginal and urine specimens was 97% (93–99%); 94% (88–99%) and 83% (75–92%), respectively. The sensitivity (95% CI) of the DFA test for cervical, vaginal and urine specimens was 93% (87–99%); 92% (86–99%) and 78% (68–88%), respectively. Concordance between the LCR and DFA test results was very high for specimens from the same site. The results indicate that nucleic acid amplification tests are appropriate for screening women seeking TOP and, indeed, other women in early pregnancy. The sensitivity of the LCR test for urine specimens was less, but the high levels of concordance observed between the LCR and DFA test results for urine specimens indicates that this was due to a lower organism load rather than inhibition of the LCR.
Patient-initiated digital photography in Peyronie's disease
Authors: Obeyesekera S , Herdiman J , Goh B T
Published: June 2006

The introduction of digital camera and phone camera without having to develop images by a third party has simplified photography for everyday use. Digital imaging by patients can assist the assessment of medical conditions. We describe four male patients attending our department in whom digital imaging initiated by the patients was deemed to be helpful in supporting the diagnosis and assessing the severity of Peyronie's disease.
An unusual differential diagnosis of penile warts: metastases from rectal carcinoma
Authors: Cathomas R , Geldart T R , Iveson T , Singh N , Rowen D
Published: June 2006

Patients with penile lesions, such as virally induced papillomata, frequently present to genitourinary medicine clinics and general practitioners. Their diagnosis is usually based on clinical observation and biopsy is not generally undertaken. Penile lesions may rarely have a more sinister aetiology and represent metastatic spread from solid tumours arising at distant sites. Penile metastases arise most frequently from genitourinary cancers (prostate, bladder and kidney), but may also arise from tumours of the large bowel; other primary sites are extremely uncommon. We report the case of a patient presenting with penile metastases from rectal carcinoma arising during third-line chemotherapy for metastatic disease.
Poly-L-lactic acid for treating HIV-associated facial lipoatrophy: a review of the clinical studies
Authors: Barton S E , Engelhard P , Conant M
Published: June 2006

Facial lipoatrophy can be associated with human immunodeficiency virus (HIV), impacting severely on quality of life. Various treatments have been investigated, including poly-L-lactic acid (PLLA). Four studies have investigated the efficacy of PLLA in the correction of HIV-associated facial lipoatrophy. The studies: VEGA, Chelsea and Westminster, APEX002 and Blue Pacific involved 50, 30, 99 and 99 patients, respectively, exhibiting HIV-associated facial lipoatrophy. Follow-up ranged from 24–96 weeks. Measures of treatment efficacy included ultrasound and subjective measures. Significant, long-lasting increases in dermal thickness were recorded and in all four studies, a subjective improvement was reported by patients and investigators in facial appearance and quality of life. Treatment was well tolerated. Small, non-bothersome subcutaneous papules were the only device-related adverse events observed. PLLA represents a promising treatment option for HIV-associated facial lipoatrophy. The procedure requires minimal 'downtime' and provides long-lasting results without the need for invasive surgery.
Capacity of health-care facilities to deliver HIV treatment and care services, Northern Tanzania, 2004
Authors: Landman Keren Z , Kinabo Grace D , Schimana Werner , Dolmans Wil M , Swai Mark E , Shao John F , Crump John A
Published: June 2006

Few data exist on the current capacity of Tanzanian health-care facilities to deliver antiretroviral therapy (ART). We evaluated this capacity among Northern Zone facilities in 2004 using a questionnaire that addressed human resources, clinical facilities and services, and laboratory capacity. Of 19 facilities surveyed, nine (47%) had staff trained to manage ART and three (16%) prescribed ART. Two (11%) offered CD4 counts, five (26%) offered liver function tests, 16 (84%) offered chest radiography, and 18 (95%) offered acid-fast sputum staining. Of 12 (67%) facilities offering outpatient HIV/AIDS services, 12 (100%) provided co-trimoxazole to outpatients and six (50%) provided isoniazid (INH). All 19 (100%) facilities offered rapid HIV tests and full blood pictures. Overall in 2004, facilities needed strengthening to increase staff training in ART management and to implement INH for treatment of latent tuberculosis. Laboratory facilities for ART monitoring were inadequate, and outpatient ART was limited.
Comparative epidemiology of Chlamydia trachomatis infection among men attending sexually transmitted disease clinics with and without indication for testing
Authors: Rowhani-Rahbar A , Niccolai L M , Dunne D W , Green S , Jenkins H , Khoshnood K
Published: June 2006

Understanding the epidemiology of Chlamydia trachomatis infection in men without indication for testing (without symptoms, signs, or a report of sexual contact with an infected partner) is of crucial importance to reduce the heavy burden of this infection, particularly because this group of men is not usually offered testing in different clinical settings. Using electronic medical records of two STD clinics in Connecticut, 2000–02, this study identified the risk factors of C. trachomatis infection in men with and without indication for testing. In both groups, men who were younger than 30, African-American, or had a prior history of C. trachomatis infection were significantly more likely to be infected. Since a system for routine reproductive health care of young men does not currently exist, health-care providers need to promote an increased awareness of C. trachomatis infection among their male patients who are at increased risk of infection.
Self-reported anal sex practice and sexual risk-taking after marijuana use among a sample of Georgia inmates
Authors: Stephens Torrance T , Sprauve Nancy Elizabeth
Published: June 2006

The primary aim of this study was to examine factors related to anal sex practices and sexual risk-taking among a sample of soon-to-be-released adult male inmates with respect to self-reported HIV/AIDS risk behaviours. This study focused on collecting data from adult male inmates during the period from 2000 to 2003. Baseline level data were collected by project staff after a pool of eligible participants was selected by Department of Corrections personnel. Inmates had to be 18 years of age or older, male, and sexually active. Findings suggest that inmates did not vary much with respect to feeling that they would be less likely to take precautions before having sex after using marijuana. Inmates who reported having anal sex were more likely to indicate that they felt they were better lovers while under the influences of marijuana. Those with a history of anal sex also reported being more likely to do things sexually under the influence of marijuana than they would if they were sober ( P < 0.03).
An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women
Authors: Garland S M , Waddell R , Mindel A , Denham I M , McCloskey J C ,   The Australian Genital Warts Study Group on Imiquimod
Published: June 2006

Our objective was to determine the optimal duration of treatment with imiquimod for external genital warts over 4, 8, 12 or 16 weeks. A total of 120 women with a history of genital warts for a median of 3–6 months and prior alternative treatments in 73% were evaluated for total clearance rates. There was no statistically significant difference in complete clearance rates after 16-week follow-up across treatment groups: four weeks (40.0%), eight weeks (48.4%), 12 weeks (39.3%) and 16 weeks (51.6%). Imiquimod was well tolerated, and in those treated for four weeks there was a lower incidence of local skin reactions such as erythema and erosion, and no incidences of pain. These preliminary results suggest that a four-week treatment course of imiquimod applied thrice weekly for women with external genital warts may provide a reasonable approach with comparable efficacy and compliance, and minimal adverse events, drug costs and clinic visits.
Managing sexually transmitted infections in community sexual health clinics: an audit of a community service
Authors: Evans J , Bacon L
Published: June 2006

Traditional hospital-based genitourinary (GU) medicine services have been overwhelmed by the current sexual health crisis. In November 2001, the Community Sexual and Reproductive Health department in Lewisham, South East London started a treatment service for uncomplicated sexually transmitted infections (STI). An audit was conducted to evaluate the effectiveness of and demand for this service. Two years after its introduction the number of chlamydia tests increased by 94%, the number of men attending the service doubled, GU medicine referrals halved and the number of STI treatments had risen by 90%, mainly for chlamydia. Proposed national outcome standards were exceeded with treatment of 84% of chlamydia clients with a median delay of 14 days, partner notification documented in 88% of chlamydia treatments and 0.45 contacts per case of chlamydia treated. Community-based services can provide successful testing, treatment and partner notification for uncomplicated STI despite increasing demand and such services should be properly recognized, encouraged and financially supported.
The influence of antiretroviral therapy on the uptake of HIV testing in Tutume, Botswana
Authors: Warwick Zoe
Published: June 2006

This paper describes how the national antiretroviral (ARV) programme in Botswana has influenced the willingness of the community of Tutume District, Botswana to come forward for HIV testing. A retrospective review of Tutume Primary Hospital records was performed for three different periods: prior to the national antiretroviral therapy (ART) programme, once ART was available in limited centres and once ART was available locally. There was a five-fold increase in the number of HIV tests performed once treatment became available locally, primarily due to female voluntary testing. Access to free ART increases the HIV testing rate of previously reluctant communities.
The role of a metastable RNA secondary structure in hepatitis delta virus genotype III RNA editing
Authors: Linnstaedt Sarah D. , Kasprzak Wojciech K. , Shapiro Bruce A. , Casey John L.
Published: June 2006

RNA editing plays a critical role in the life cycle of hepatitis delta virus (HDV). The host editing enzyme ADAR1 recognizes specific RNA secondary structure features around the amber/W site in the HDV antigenome and deaminates the amber/W adenosine. A previous report suggested that a branched secondary structure is necessary for editing in HDV genotype III. This branched structure, which is distinct from the characteristic unbranched rod structure required for HDV replication, was only partially characterized, and knowledge concerning its formation and stability was limited. Here, we examine the secondary structures, conformational dynamics, and amber/W site editing of HDV genotype III RNA using a miniaturized HDV genotype III RNA in vitro. Computational analysis of this RNA using the MPGAfold algorithm indicated that the RNA has a tendency to form both metastable and stable unbranched secondary structures. Moreover, native polyacrylamide gel electrophoresis demonstrated that this RNA forms both branched and unbranched rod structures when transcribed in vitro. As predicted, the branched structure is a metastable structure that converts readily to the unbranched rod structure. Only branched RNA was edited at the amber/W site by ADAR1 in vitro. The structural heterogeneity of HDV genotype III RNA is significant because not only are both conformations of the RNA functionally important for viral replication, but the ratio of the two forms could modulate editing by determining the amount of substrate RNA available for modification.
Universal SHO and SpR shift rotas adversely influence SHO operative experience
Authors: Beaton C , Stephens MR , Hopper AN , Lewis WG
Published: June 2006

The European Working Time Directive (EWTD) will reduce the clinical experience obtained by surgeons prior to attaining consultant status from 21,000 surgical hours to 7,640 hours, 1 with shift work obligatory for compliance. We have shown previously that the operative experience of SHOs in general surgery is on the wane in our own hospital, varies with subspecialty interest 2 and has witnessed further erosion by the introduction of the EWTD. 3 The aim of this study was to assess the influence of an all tier shift rota on the emergency and elective operative experience of SHOs in a category 1 general surgical training post working in a large district general hospital serving a population of 600,000.