bluuebunny/crossref_metadata_2025 huggingface dataset:
Solvolysis of 1-[trans-2-(m- or p-Substituted Phenyl)cyclopropyl]-1-methylethyl p-Nitrobenzoates
Authors: Kusuyama Yoshiaki
Published: August 2005

The solvolyses of 1-[trans-2-(m- or p-substituted phenyl)cyclopropyl]-1-methylethyl p-nitrobenzoates in 80% aqueous acetone have been studied with regard to both reactivity and product composition. For the less reactive substituents such as m-Br, m-Cl, and m-CF3, the solvolysis products were the corresponding 2-(2-arylcyclopropyl)-2-propanol, indicating the cyclopropylmethyl cation intermediate. The ring-opened products increased as the electron-donating ability of the substituents increased. The application of the Yukawa–Tsuno equation to the reactivity afforded a ρ value of −1.43 and r value of 0.59 with a correlation coefficient of 0.997. A large value of r indicates the presence of the allylic cation intermediate where much more charge develops at the benzylic carbon for the derivatives with electron-donating substituents than is the case for the cyclopropylmethyl cation intermediate. Thus the solvolysis reaction proceeds via two independent pathways: one has a cyclopropyl cation intermediate and the other has a homoallylic cation intermediate.
The Stability of Seven-Coordinate Species of Earlier Members in the First Transition Series: Heptahydrated Ti(II), V(II), Cr(II), and Mn(II) Ions Relevant to Intermediate and Transition State in Water-Exchange Reaction
Authors: Tsutsui Yuko , Wasada Hiroaki , Funahashi Shigenobu
Published: August 2005

The structure and stability of heptahydrated divalent cations of earlier members in the first transition series ([M(H2O)7]2+: M = Ti, V, Cr, and Mn) have been studied by ab initio molecular-orbital methods, because the heptahydrated cations are relevant to intermediates and transition states in their water-exchange reactions. The structure is pentagonal bipyramidal with a distorted equatorial plane. The heptahydrated divalent cations with d0, d1, d2, and d5 configurations are at the local minima, and those with d3 and d4 are at the saddle points, though there is an increase in hydration energy across the row of the periodic table from calcium to zinc. The trend of stability in a series of heptahydrated divalent cations strongly depends on the d-electron configuration, and differs significantly in the case of the penta- or hexahydrated cations that are at the local minima. It is concluded that an associative mechanism is possible for the water-exchange reaction on hexahydrated divalent cations of the earlier members in an aqueous solution.
Lithiosilanes with Si–Si Bonds: Synthesis and 6Li, 7Li, and 29Si NMR Studies
Authors: Nanjo Masato , Sekiguchi Akira , Sakurai Hideki
Published: August 2005

Lithiopentamethyldisilane (LiSiMe2SiMe3, 1a), two isomer of lithioheptamethyltrisilane (LiSiMe2SiMe2SiMe3, 1b; LiSi(SiMe3)2Me, 1c), lithio[tris(trimethylsilyl)]silane (LiSi(SiMe3)3, 1d), 2-lithio-1,3-diphenylpentamethyltrisilane (LiSi(SiMe2Ph)2Me, 1e), 2-lithio-2-phenylhexamethyltrisilane (LiSi(SiMe3)2Ph, 1f), 3-lithio-1,5-diphenylnonamethylpentasilane (LiSi(SiMe2SiMe2Ph)2Me, 1g), lithio[bis(dimethlphenylgermyl)]methylsilane (LiSi(GeMe2Ph)2Me, 1h), and lithiotrimethylsilane (LiSiMe3, 3) were prepared by lithium–mercury exchange reactions. The unsolvated lithiosilanes exist as the aggregated oligomers in non-polar solvents, whereas those solvated by THF or Et2O exist as monomers. Synthesis and detailed spectroscopic studies of the lithiosilanes with Si–Si bonds are reported.
Dimensiosolvatic Effects. III. Quantification of Dimensiosolvatic Effects by Solvolyses of 2-Bromoadamantane in Water–Alcohol Mixtures
Authors: Oki Michinori , Ikeda Hiroshi , Toyota Shinji
Published: August 2005

Solvolyses of 2-bromoadamantane in aqueous alcohols were carried out to find the selectivities, kether/kalcohol, at various concentrations of water in an alcohol and at various temperatures. While the observed ratios contain a large error or fluctuate at low concentrations of water, they were almost constant for 1.0 : 0.8 alcohol/water mixtures. The selectivity was also independent of temperatures of the reaction. The significance of the selectivity, which is determined by the ease of solvent intervention into contact ion pairs, is discussed. D values, which are obtained by taking reciprocals of the selectivity for the 1.0 : 0.8 mixture, are proposed as a measure of the dimensiosolvatic effects when a solvent molecule intervenes into the contact ion pair.
Efficient Dimerization of Propene by Nickel-Phosphine Catalysis in the Presence of Sulfonic Acids and/or Dialkyl Sulfates. Effects of Phosphine Ligands and Additives
Authors: Itagaki Makoto , Suzukamo Gohfu , Nomura Kotohiro
Published: August 2005

The effect of the phosphines for the dimerization of propene using a nickel catalyst system consisting of nickel naphthenate, tertiary phosphine (PCy3, P(i-Pr)3, PEt3, PEt2Ph, and PPh3; Cy = cyclohexyl), triethylaluminum, and 2,4,6-trichlorophenol in the presence of sulfonic acids and/or dialkyl sulfates was investigated. A remarkable increase in both the catalytic activity (turnover number (TON) for the formation of C6 olefins) and the selectivity of dimers (selectivity of dimers based on the propene reacted) was observed, especially upon the addition of sulfonic acids, such as MeSO3H, CF3SO3H, and/or dialkyl sulfates (Me2SO4 or Et2SO4). The reaction products formed by the above catalyst system with PEt3 and PEt2Ph were exclusively C6 olefins (selectivity of dimers: 97 and 93%, respectively). It was also revealed in this catalyst system that the electronic factor of phosphine is important for the catalytic activity, and that the dimer’s proportion greatly depends upon the kind of phosphine used.
Fluorescence Detection of Hybrid Formation between Pyrrolidine-based Oxy-peptide Nucleic Acid and DNA
Authors: Kitamatsu Mizuki , Shigeyasu Masanori , Sisido Masahiko
Published: August 2005

When an oxy-peptide nucleic acid that contains pyrrolidine rings (pyrrolidine-based oxy-PNA = POPNA) hybridized with its complementary DNA, a fluorophore, DiSC2(5), bound specifically to the hybrid in aqueous solution. Free DiSC2(5) did not fluoresce by itself, but the bound DiSC2(5) showed strong fluorescence. The fluorescence was observed only on a fully-matched POPNA–DNA hybrid, but not on hybrids with even single mismatches. This finding provides bases for highly sensitive and highly specific detection of single nucleotide polymorphisms.
Chiral Bis-phosphoramidites Based on Linked-BINOL for Rhodium-catalyzed 1,4-Addition of Arylboronic Acids to α,β-Unsaturated Carbonyl Compounds
Authors: Yamamoto Yasunori , Kurihara Kazunori , Sugishita Noriyuki , Oshita Kengo , Piao Dongguo , Miyaura Norio
Published: August 2005

Cationic rhodium(I) complex prepared from Shibasaki’s linked-BINOL and [Rh(nbd)2]BF4 catalyzed asymmetric 1,4-addition of arylboronic acids to enones at room temperature with high enantioselectivities up to 99.8%ee.
Chemoselective Oxidation of Sulfides to Sulfoxides Using N-t-Butyl-N-chlorocyanamide
Authors: Kumar Vinod , Kaushik Mahabir Parshad
Published: August 2005

A simple, efficient and highly chemoselective method has been developed for the synthesis of sulfoxides from sulfides using N-t-butyl-N-chlorocyanamide as an oxidant in a mixed acetonitrile–water solution with a 1:1 mol ratio of oxidant to sulfides. N-t-butyl-N-chlorocyanamide, a source of positive chlorine, has been used for conversion of the variety of sulfides into their corresponding sulfoxides in quantitative yields.
The Prevalence of Suicidal Phenomena in Adolescents: A Systematic Review of Population‐Based Studies
Authors: Evans Emma , Hawton Keith , Rodham Karen , Psychol C. , Deeks Jonathan
Published: August 2005

The results of a systematic review of the international literature on the prevalence of suicidal phenomena in adolescents, including the influence of survey method, gender, and ethnicity are reported. The literature was searched using six electronic databases to identify all population‐based studies of self‐reported suicidal phenomena; 128 studies were included, comprising 513,188 adolescents. The mean proportion of adolescents reporting they had attempted suicide at some point in their lives was 9.7% (95% CI, 8.5–10.9), and 29.9% (95% CI, 26.1–33.8) of adolescents said they had thought about suicide at some point. Females were significantly more likely than males to report most suicidal phenomena. A lower prevalence of some suicidal phenomena was found for Asian populations. The prevalence of suicidal phenomena varied depending on the terminology used and tended to be higher in studies employing anonymous questionnaires than in studies employing non‐anonymous methods (questionnaires or interviews), although most of these differences were not statistically significant.
Theoretical investigations of the reactivity of MO4 and the electronic structure of Na2[MO4(OH)2], where M=Ru, Os, and Hs (element 108)
Authors: Pershina V.
Published: August 2005

Fully relativistic, four-component, density functional theory calculations (4c-DFT) were performed for [MO4(OH)2]2- and Na2[MO4(OH)2], where M=Ru, Os, and Hs. The electronic structure of the Hs complex ion was shown to be similar to that of the Os complex ion, though [HsO4(OH)2]2- should be more covalent than the lighter congeners in group 8, by analogy with MO4. The calculations of the free energy change, Δ G
r, of the [MO4(OH)2]2- and Na2[MO4(OH)2] formation reactions from the volatile tetroxides and NaOH have shown that HsO4 should be slightly less reactive than OsO4, with the difference in ΔG
r being less than 52 kJ/mol. In the experimental study of the deposition of OsO4 and HsO4 on the surface of NaOH in the presence of water, such a difference in reactivity has not yet been clearly revealed. The anionic complex of Ru(VIII) was found to be much less stable than those of Os and Hs. Also, Delta;G
r for the formation of [RuO4(OH)2]2- from RuO4 was found to be ∼300 kJ/mol more positive than ΔG
r for analogous reactions of Os and Hs, which explains why the Ru(VIII) complex is not known. The ionic radii, IR(Hs8+)=0.454 Å for CN=4, IR(Os8+) = 0.49 Å and IR(Hs8+) = 0.54 Å for CN=6, have been obtained on the basis of the calculations of bond lengths in MO4, as well as via a correlation between R
max of the outer np obitals and IR of the 5d and 6d elements, respectively.
Sorption of U(VI) species on hydroxyapatite
Authors: Thakur P. , Moore R. C. , Choppin G. R.
Published: August 2005

The sorption of uranyl (UO22+) cations to hydroxyapatite was studied as a function of the amount of sorbent, ionic strength, U(VI) concentration, pH and temperature. The rate of uranyl sorption on hydroxyapatite decreased with increased uranyl concentrations. The amount sorbed decreased with increased ionic strength and increased with pH to a maximum at 7–8. The sorption data for UO22+were fitted well by the Freundlich and Dubinin–Radushkevich (D–R) isotherms. The anions Cl−, NO3−, SO42-and CH3COO−decreased the sorption of uranium on hydroxyapatite while S2O32-slightly increased it. The sorbed uranium was desorbed by 0.10 M and 1.00 M solutions of HCl and HNO3.

The thermodynamic parameters for the sorption of UO22+were measured at temperatures of 298, 313, 323 and 333 K. The temperature dependence confirmed an endothermic heat of sorption. The activation energy for the sorption process was calculated to be +2.75±0.02 kJ/mol.
Synthesis and biodistribution of 99mTc-Vancomycin in a model of bacterial infection
Authors: Roohi Samina , Mushtaq A. , Malik Salman A.
Published: August 2005

Vancomycin Hydrochloride is an antibiotic produced by the growth of certain strains of Streptomyces orientalis. As Vancomycin Hydrochloride is poorly absorbed after oral administration; it is given intravenously for therapy of systemic infections. Vancomycin was labeled with technetium-99m pertechnetate using SnCl2·2H2O as reducing agent. The labeling efficiency depends on ligand/reductant ratio, pH, and volume of reaction mixture. Radiochemical purity and stability of 99mTc-Vancomycin was determined by thin layer chromatography. Biodistribution studies of 99mTc-Vancomycin were performed in a model of bacterial infection in Sprague–Dawley rats. A significantly higher accumulation of 99mTc-Vancomycin was seen at sites of S. aureus infected animals. Whereas uptake of 99mTc-Vancomycin in turpentine inflamed rats were quite low.
Prospects and problems in the production of 143Pr for radionuclide therapy applications
Authors: Vimalnath K. V. , Das M. K. , Venkatesh Meera , Ramamoorthy N.
Published: August 2005

Praseodymium-143 (T
1/2=13.57 d and E
β(max)= 0.937 MeV) is the beta decay product of 143Ce (T
1/2=33.04 h) and would provide an ideal complement to the widely used 32P (T
1/2= 14.3 d, E
β(max)=1.71 MeV), for some applications in radionuclide therapy (RNT), as it has a lower beta energy, but comparable half-life. For the production of 143Pr, 10-500 mg of two cerium compounds, ceric ammonium sulphate and ceric oxide, were irradiated in the reactor for 7 days at a neutron flux of ∼1×1013 n cm−2 s−1. After five days of post irradiation cooling, the samples were dissolved in appropriate reagents and aliquots drawn were subjected to high resolution gamma ray spectrometry for assay of activity and radionuclide purity. 7.4 MBq 143Ce per mg ceric oxide was produced under the aforesaid conditions along with other long-lived isotopes of cerium. An effort was made for the separation of no-carrier added (nca) 143Pr in order to study its utility for radionuclide therapy (RNT). A maximum yield of ∼450 MBq of 143Pr was obtained at calibration time defined as 7 d from end of irradiation (EOI). Hydroxyapatite (HA) was labeled with 143Pr at pH 5–6 and greater than 99.5% of 143Pr activity remained bound to HA even after 90 h post labeling. Despite the low cross-section of 142Ce(n,γ) reaction (0.1 barn) and isotopic abundance of 142Ce in natural targets (11.114%) being inherent disadvantages in large scale production of 143Pr, therapies needing low to medium doses would benefit from the use of ‘nca’ 143Pr.
Steroid withdrawal syndrome after successful treatment of Cushing’s syndrome: a reminder
Authors: Bhattacharyya A , Kaushal K , Tymms D J , Davis J R E
Published: August 2005

Steroid withdrawal syndrome (SWS) usually refers to relapse of the disease being treated after withdrawal of glucocorticoid therapy, or the symptoms of adrenal insufficiency which occur when glucocorticoids are rapidly reduced or stopped. A less well-recognised form of SWS is that which develops when patients experience a symptom complex similar to that of adrenal insufficiency despite acceptable cortisol levels. We describe three patients who presented with this form of SWS following surgical treatment for endogenous Cushing’s syndrome. All responded well to a short-term increase in the dose of glucocorticoid replacement therapy, with the median duration of the syndrome being 10 months (range 6–10 months). Trough serum cortisol levels above 100 nmol/l, with peaks between 460 and 750 nmol/l were documented in the first two patients at presentation with SWS. It is thought that the syndrome may result from development of tolerance to glucocorticoids, and mediators considered to be important in its development include interleukin-6, corticotrophin-releasing hormone, vasopressin, and central noradrenergic and dopaminergic systems. The exact underlying mechanism for SWS remains unclear. However, with increasing recommendations for use of lower doses of replacement glucocorticoids, its incidence may increase. Physicians need to be aware of this condition, which is self-limiting and easily treated by a temporary increase in the dose of glucocorticoid replacement therapy. It is possible that a slower glucocorticoid tapering regimen than that used in the standard postoperative management of patients undergoing pituitary surgery may reduce the risk of development of SWS.
Persistent diastolic dysfunction despite successful long-term octreotide treatment in acromegaly
Authors: van Thiel S W , Bax J J , Biermasz N R , Holman E R , Poldermans D , Roelfsema F , Lamb H J , van der Wall E E , Smit J W A , Romijn J A , Pereira A M
Published: August 2005

Introduction: This study was designed to evaluate potential reversibility of left-ventricular (LV) dysfunction in patients with acromegaly following long-term control of disease. It is unknown whether the cardiac changes induced by acromegaly can be reversed completely by long-term strict control of growth hormone excess by octreotide.

Patients and methods: We compared LV systolic and diastolic function in inactive patients with acromegaly (n = 22), who were divided into patients with long-term control by octreotide (n = 14) and patients with long-term cure by surgery/radiotherapy (n = 8). We also assessed these parameters in patients with active acromegaly (n = 17).

Results: In patients with active acromegaly, systolic function at rest was decreased by 18% (P < 0.01), LV mass index increased by 40% (P < 0.04) and isovolumetric relaxation time increased by 19% (P < 0.01), compared with patients with inactive acromegaly. These parameters were not different between well-controlled and cured patients. Using tissue Doppler imaging, the ratio between early and late diastolic velocity (E′/A′ ratio) was decreased in active, compared with inactive acromegaly (0.75±0.07 versus 1.24±0.15; P < 0.01). This E′/A′ ratio was considerably higher in cured, compared with octreotide-treated, patients (1.75±0.41 versus 1.05±0.1; P < 0.01).

Conclusion: Diastolic function is persistently and significantly more impaired in acromegalic patients with long-term control by octreotide than in surgically cured patients, which points to biological effects of subtle abnormalities in growth hormone secretion. Criteria for strict biochemical control of acromegaly should thus be reconsidered.
Testosterone substitution with a new transdermal, hydroalcoholic gel applied to scrotal or non-scrotal skin: a multicentre trial
Authors: Kühnert B , Byrne M , Simoni M , Köpcke W , Gerss J , Lemmnitz G , Nieschlag E , _ _
Published: August 2005

Objective: Testosterone-containing gels have improved testosterone substitution therapy, but they are associated with the risk of interpersonal transfer. Therefore, we tested a new hydroalcoholic 2.5% testosterone gel (TGW), which was removed by washing 10 min after administration.

Design: The gel was applied to scrotal or non-scrotal skin in comparison to two 2.5 mg Androderm® patches in a randomised, three-arm, parallel-group, controlled multicentre trial over a period of 24 weeks. We included symptomatic hypogonadal men whose morning testosterone levels were <10 nmol/l. Either 1 g TGW was applied to scrotal skin (n = 54) or 5 g to non-scrotal skin (n = 56) once daily; the patch group (n = 52) applied two patches/day. Dose titration was allowed.

Results: Whereas serum testosterone levels and the pre-post changes of the areas under the curve of testosterone and free testosterone between weeks 0 and 24 indicated equivalent treatment success for the patch and scrotal groups, the dermal gel group was significantly superior to the other two groups. Questionnaires on sexual function, mood and quality of life did not differ significantly between study groups, nor were prostate volume, prostate-specific antigen (PSA) levels and prostate symptoms different. However, tolerability was much better in the gel groups than the patch group.

Conclusion: Efficacy, safety and tolerability suggest TGW as a favourable treatment for hypogonadal patients.
Polyethylene glycol-conjugated growth hormone-releasing hormone is long acting and stimulates GH in healthy young and elderly subjects
Authors: Munafo A , Nguyen T X Q , Papasouliotis O , Lécuelle H , Priestley A , Thorner M O
Published: August 2005

Objective: The clinical use of growth hormone-releasing hormone (GHRH) is limited by its short half-life. Polyethylene glycol-conjugated GHRH (PEG-GHRH) was developed to provide increased stability compared with the currently available GHRH(1–29). This study aimed to evaluate the safety, tolerability and pharmacodynamics of PEG-GHRH.

Design: PEG-GHRH was administered by subcutaneous injection to young healthy men (n = 12) and elderly men and women (aged > 60 years; n = 20).

Results: In both groups, administration of PEG-GHRH generated a clear increase in circulating GH compared with placebo. Following single-dose (0.25, 0.5, 2 or 4 mg) administration to young subjects, the effect persisted for 12 h, but a sustained increase was observed on repeated administration to the elderly. Serum insulin-like growth factor-I also increased in response to PEG-GHRH treatment. Injection-site reactions were more frequent with PEG-GHRH compared with placebo, but these were mild and transient; other adverse events were similar to those observed after placebo. Some impairment of glucose tolerance was observed in the elderly following repeated administration of PEG-GHRH. Antibodies to GHRH were not observed.

Conclusions: PEG-GHRH offers the possibility of less frequent dosing compared with GHRH. This possibility deserves further clinical testing.
Duct ligation and pancreatic islet blood flow in rats: physiological growth of islets does not affect islet blood perfusion
Authors: Jansson Leif , Bodin Birgitta , Källskog Örjan , Andersson Arne
Published: August 2005

Objectives: The aim of this study was to evaluate islet blood-flow changes during stimulated growth of the islet organ without any associated functional impairment of islet function.

Design: A duct ligation encompassing the distal two-thirds of the pancreas was performed in adult, male Sprague–Dawley rats.

Methods: Pancreatic islet blood flow was measured in duct-ligated and sham-operated rats 1, 2 or 4 weeks after surgery. In some animals studied 4 weeks after surgery, islet blood flow was also measured also during hyperglycaemic conditions.

Results: A marked atrophy of the exocrine pancreas was seen in all duct-ligated rats. Blood glucose and serum insulin concentrations were normal. An increased islet mass was only seen 4 weeks after surgery. No differences in islet blood perfusion were noted at any time point after duct ligation. In both sham-operated and duct-ligated rats islet blood flow was increased during hyperglycaemia; the response was, however, slightly more pronounced in the duct-ligated part of the gland.

Conclusions: Normal, physiological islet growth does not cause any major changes in the islet blood perfusion or its regulation. This is in contrast to findings during increased functional demands on the islets or during deteriorated islet function, when increased islet blood flow is consistently seen.
Subtle hyperproinsulinaemia characterises the defective insulin secretory capacity in offspring of glutamic acid decarboxylase antibody-positive patients with latent autoimmune diabetes mellitus in adults
Authors: Vauhkonen Ilkka , Niskanen Leo , Knip Mikael , Mykkänen Leena Moilanen , Haffner Steven , Uusitupa Matti , Laakso Markku
Published: August 2005

Objective: We set out to assess whether hyperproinsulinaemia is an early finding in latent autoimmune diabetes in adults (LADA).

Research design and methods: We measured plasma proinsulin and C-peptide responses during a 2-h oral glucose tolerance test (OGTT) and in the hyperglycaemic clamp in 21 normoglycaemic offspring of LADA patients testing positive for glutamic acid decarboxylase antibodies (GADA) or islet cell antibodies (ICA), and in 17 healthy control subjects without a family history of diabetes.

Results: The study groups had comparable areas under the curves of blood glucose, plasma proinsulin, C-peptide and proinsulin/C-peptide in the OGTT. However, the offspring of LADA patients had higher proinsulin/C-peptide in the hyperglycaemic clamp (P < 0.01 versus the control group). The offspring of GADA-positive LADA patients (n = 9) had higher proinsulin and proinsulin/C-peptide than did the control group in the OGTT (P < 0.05 for both comparisons) and in the hyperglycaemic clamp (P < 0.001 and P < 0.05 respectively). They also had higher proinsulin than the offspring of ICA-positive LADA patients (n = 12) (P < 0.001) in the hyperglycaemic clamp. The offspring of ICA-positive LADA patients did not clearly show hyperproinsulinaemia during the tests, but they had lower maximal glucose-stimulated insulin secretory capacity than the control group (P < 0.05) and the offspring of GADA-positive LADA patients (P < 0.05) in the hyperglycaemic clamp.

Conclusions: These results suggested that insulin secretion in the offspring of GADA-positive LADA patients is characterised by subtle defects in the processing of insulin precursors. Furthermore, various proinsulin responses among the offspring of LADA patients with different autoimmune markers provided further evidence that LADA is a heterogeneous disorder.
Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in postmenopausal women
Authors: Schuit Stephanie C E , de Jong Frank H , Stolk Lisette , Koek W Nadia H , van Meurs Joyce B J , Schoofs Mariette W C J , Zillikens M Carola , Hofman Albert , van Leeuwen Johannes P T M , Pols Huibert A P , Uitterlinden André G
Published: August 2005

Objective: Postmenopausal estradiol (E2) levels vary widely between individuals and this variation is an important determinant of diseases such as osteoporosis. It has been suggested that the estrogen receptor alpha (ESR1) gene may influence peripheral E2 levels, but the role of common sequence variations in the ESR1 gene is unclear.

Methods: In 631 postmenopausal women and 528 men from the Rotterdam Study, a population-based, prospective cohort study of individuals aged 55 years and over, ESR1 PvuII-XbaI haplotypes were determined and correlated with plasma E2 levels.

Results: In women, haplotype 1 (T-A) was significantly associated with an allele-dose-dependent decrease in E2. After adjusting for age, body mass index, years since menopause and testosterone levels, plasma E2 levels decreased by 1.90 pmol/l per allele copy of this haplotype (P < 0.05). Extreme genotypes, representing 23 and 27% of the population, varied by 3.93 pmol/l. No association with plasma testosterone was observed. In a subset of 446 women, no association of genotype with plasma concentrations of dehydroepiandrosterone sulfate, androstenedione or estrone was seen. In men, none of the sex hormone levels was associated with the ESR1 PvuII-XbaI haplotypes.

Conclusion: We have demonstrated a role for genetic variations in the ESR1 gene in determining post-menopausal E2 levels in women.
Effect of Oxygen Management on Culture Performance of Channel Catfish in Earthen Ponds
Authors: Torrans Eugene L
Published: August 2005

Aeration allows for higher feeding rates and increased production of channel catfish Ictalurus punctatus in intensive and semi-intensive aquaculture systems. However, the effect of specific dissolved oxygen (DO) concentrations on various production parameters remains unknown. The purpose of this 2-year study was to determine the effect of daily minimum DO concentration on channel catfish production. Six 0.1-ha ponds were each equipped with three 0.37-kW (0.5-hp) aerators and one 0.37-kW circulator. Dissolved oxygen concentrations were monitored and recorded with a commercial oxygen monitor that also controlled aeration. During both years, aeration in the high-oxygen treatment was initiated when the DO concentration dropped below 5.0 mg/L (mean, 64% saturation from May to September); aeration in the low-oxygen treatment was initiated when the DO concentration dropped below 2.5 mg/L (32% saturation; 2001) or 1.5 mg/L (19% saturation; 2002). The minimum DO concentrations resulting from this aeration protocol differed somewhat from aerator set points. In the low-oxygen treatment, delaying aeration until the DO concentration dropped below 2.5 mg/L reduced feed consumption by 6% relative to the high-oxygen treatment. Other production parameters were not significantly different. In 2002, when aeration was delayed until the DO concentration dropped below 1.5 mg/L, the low-oxygen treatment group exhibited reductions in food consumption (45% less than consumption by the high-oxygen treatment), average fish weight (31% less), and net production (54% less). Even at the high feeding rates of 2002 (maximum of 680 kg · ha−1 · d−1; 44,066 kg/ha total in one pond), other water quality variables were acceptable. Net production in the high-oxygen treatment in 2002 averaged 23,547 kg/ha, a potential record for channel catfish in earthen ponds. Neither the feed conversion ratio nor survival was significantly different between treatments in either year. While these results cannot be directly extrapolated to large commercial ponds, it appears that increased aeration may increase production well above current commercial levels.
Rearing in Enriched Hatchery Tanks Improves Dorsal Fin Quality of Juvenile Steelhead
Authors: Berejikian Barry A
Published: August 2005

The present study compared the dorsal fin condition of juvenile steelhead Oncorhynchus mykiss reared in conventional hatchery tanks, enriched hatchery tanks (i.e., with the addition of submerged structure, overhead cover, and underwater feeders), and a natural stream to determine whether structural enrichment would reduce dorsal fin erosion in hatchery-reared fish. Dorsal fin height at 27 d postemergence did not differ significantly between the two hatchery rearing treatments. Steelhead reared in the conventional tanks had dorsal fins 78% as long as steelhead reared in enriched tanks and in the natural stream at 50 d postemergence (P < 0.05) and 45–55% as long at 64 d postemergence (P < 0.05). Variation in fin length did not substantially affect the ability to achieve dominance in agonistic contests for feeding territories; fish with longer dorsal fins won approximately 57% of contests against fish with fins that were 25% shorter on average. Rearing methods (such as structural enrichment), that simultaneously improve several attributes of juvenile salmonid morphology, physiology, or behavior may be important in the development of conservation hatchery rearing strategies.
Ichthyophonus in Puget Sound Rockfish from the San Juan Islands Archipelago and Puget Sound, Washington, USA
Authors: Halos Daniel , Hart S. Alexandra , Hershberger Paul , Kocan Richard
Published: August 2005

In vitro explant cultures identified Ichthyophonus in 10.9% of 302 Puget Sound rockfish Sebastes emphaeus sampled from five sites in the San Juan Islands archipelago and Puget Sound, Washington, in 2003. None of the infected fish exhibited visible lesions and only a single fish was histologically positive. Significantly more females were infected (12.4%) than males (6.8%), and while infected males were only detected at two of the five sites, infected females were identified at all sites, with no significant differences in infection prevalence. Genomic sequences of Ichthyophonus isolates obtained from Puget Sound rockfish, Pacific herring Clupea pallasii, and Yukon River Chinook salmon Oncorhynchus tshawytscha were identical in both the A and B regions of the small subunit 18S ribosomal DNA but were different from Ichthyophonus sequences previously isolated from four different species of rockfish from the northeastern Pacific Ocean. Ich-thyophonus in Puget Sound rockfish may not have been previously detected because the infection is subclinical in this species and earlier investigators did not utilize in vitro techniques for diagnosis of ichthyophoniasis. However, since clinical ichthyophoniasis has recently been identified in several other species of northeast Pacific rockfishes, it is hypothesized that this either is an emerging disease resulting from changing marine conditions or the result of introduction by infected southern species that appear during periodic El Niño events.
Water Temperature Affects a Host–Parasite Interaction: Tubifex tubifex and Myxobolus cerebralis
Authors: Kerans Billie L. , Stevens Richard I. , Lemmon J. C.
Published: August 2005

The aquatic oligochaete worm Tubifex tubifex is an obligate host of Myxobolus cerebralis, the causative agent of salmonid whirling disease. Tubifex tubifex becomes infected by ingesting M. cerebralis myxospores and releases triactinomyxons (TAMs) into the water that then infect salmonids. In a laboratory experiment, we examined how water temperature influenced changes in oligochaete population size and biomass and the release of TAMs in three genetically identified strains of T. tubifex when exposed and not exposed to M. cerebralis myxospores. Increases in population size and biomass were greatest at 8.0°C for the Gallatin River strain, greatest at 15.0°C for the Madison River strain, and similar at both temperatures for the Mt. Whitney strain. After exposure to M. cerebralis myxospores, Mt. Whitney and Madison River T. tubifex both released TAMs at 15°C beginning on day 88 and at 8.0°C on day 169 (Mt. Whitney strain) and day 182 (Madison River strain); thus, between 1,320 and 1,456 degree-days were required for M. cerebralis to develop. Gallatin River T. tubifex did not release TAMs. We found no evidence that M. cerebralis developed differently in strains of T. tubifex with different temperature requirements; therefore, it appears that temperature-driven parasite development rates are a primary determinant of the timing of TAM release.
‘Heroism displayed’: revisiting the Franklin Gallery at the Royal Naval Exhibition, 1891
Authors: Lewis-Jones Huw W.G.
Published: August 2005

The Royal Naval Exhibition (RNE) of 1891 offers an important entry point for the study of naval mythmaking. Scrutinising one part of the RNE showcase, ‘The Franklin Gallery,’ highlights the imaginative potential of the polar regions as a resource for imperial visions. This paper provides a review of the RNE and, more closely, considers the ideology of polar exploration in the context of political debate and naval reforms. The utility of images of the Arctic presented at the RNE is discussed, in particular, its role in displaying the ‘heroic martyrdom’ of Sir John Franklin (1786–1847). The paper draws upon an extensive study of late nineteenth-century newspapers, illustrated weeklies, periodical reviews, popular adult and juvenile literature, art, poetry, pamphlets, exhibition catalogues and handbooks, and associated ephemera. It argues that the RNE played a central part in the construction and enshrining of narratives of naval and national achievement in the late-Victorian period and in reviving a British commitment to the exploration of the polar regions.
The text of Joseph Shackleton's account of his visit to Iceland, 1861
Authors: Stone Ian R.
Published: August 2005

Joseph Shackleton, an older relative of Sir Ernest Shackleton, visited Iceland with two friends in 1861. They travelled in Arcturus, a Danish vessel that ran a scheduled service in summer. They visited the two main local ‘attractions,’ Thingvellir and the geysers. Shackleton kept a detailed manuscript account of the trip, which is presented in its entirety. The manuscript shows that tourism was already developed in Iceland, with an infrastructure that was in place and efficient. His account also provides interesting information concerning contemporary Iceland.
A new bipolar map projection
Authors: Rees W.G.
Published: August 2005

This paper discusses map projections suitable for representing the whole of the Earth's surface while drawing particular attention to the polar regions, and proposes a new projection. The projection is a latitudinally distorted variant of the transverse Mollweide projection, relative to which it roughly doubles the linear scale and trebles the areal coverage of the polar regions. It was adopted by the Scott Polar Research Institute in 2005.
TRPV1 activation results in disruption of the blood–brain barrier in the rat
Authors: Hu De‐En , Easton Alexander S , Fraser Paul A
Published: August 2005

We have examined the role of TRPV1 activation in disrupting the blood–brain barrier by measuring the permeability of single pial venular capillaries in anaesthetized rats.

Capsaicin application to the brain surface resulted in increased permeability, maximal 2.1±0.12 × 10−6 cm s−1 (mean±s.e.m.) with log EC50 −4.5±0.10. Substance P methyl ester gave a similar response (maximal 2.0±0.07, n=6, log EC50 −4.8±0.07), but the selective NK2 agonist, β‐Ala8‐NKA4–10 peptide, had no effect. Although CGRP decreased the permeability of venules (log EC50 10.3±0.11), its receptor antagonist CGRP8–37 had no effect on the response to capsaicin.

The TRPV1 antagonist capsazepine (1 mM) reduced the response to capsaicin (100 μM), from 1.78±0.15 to 0.63±0.10 (n=4). The NK1 receptor antagonists GR205171 (100 μM) and SDZ NKT 376 (1 mM) also reduced the response to capsaicin (from 1.75±0.14 to 0.46±0.08; n=6, and from 1.85±0.13 to 0.48±0.05; n=5, respectively), indicating that capsaicin acts via TRPV1 in series with NK1.

Starch microspheres were used to produce transient focal ischaemia. Permeability was increased on reperfusion to a greater extent and more rapidly in vessels with diameter greater than 40 μm than those less than 15 μm. Capsazepine given intraperitoneally during ischaemia reduced the permeability increase in small venules from 5.9±0.3 to 2.4±0.1, and from 11.4±0.8 to 5.1±0.9 in large venules.

In conclusion, the TRPV1 receptor is active in the brain microvasculature and has its permeability‐increasing effect via substance P. It also plays a role in the immediate blood–brain barrier disruption following ischaemia–reperfusion.

British Journal of Pharmacology (2005) 146, 576–584. doi:10.1038/sj.bjp.0706350
Reduction of repolarization reserve by halothane anaesthesia sensitizes the guinea‐pig heart for drug‐induced QT interval prolongation
Authors: Takahara Akira , Sugiyama Atsushi , Hashimoto Keitaro
Published: August 2005

The utility of halothane‐anaesthetized guinea‐pigs as an in vivo model for predicting the clinical potential of a drug to induce QT interval prolongation was assessed using the electrocardiogram and monophasic action potential (MAP) recordings with electrical ventricular pacing.

Intravenous administration of D‐sotalol (0.3 mg kg−1) and terfenadine (0.3 mg kg−1), blockers of a rapid component of delayed rectifier potassium currents, prolonged the QT interval by 32±7 and 23±6 ms, respectively, whereas chromanol 293B (1 mg kg−1), a blocker of a slow component of delayed rectifier potassium currents, lengthened it by 33±8 ms. The extent of the QT interval prolongation by these drugs was greater than those in previous reports using pentobarbital‐anaesthetized guinea‐pigs.

The MAP duration at the control was shortened by decreasing the pacing cycle length from 400 to 200 ms, but the MAP duration at each cycle length was prolonged by D‐sotalol.

The formulas of Van de Water, Matsunaga, Fridericia and Bazett showed good correlation of the repolarization period when compared with the MAP duration at a pacing cycle length of 400 ms.

The halothane‐anaesthetized guinea‐pig model may possess enough sensitivity to detect drug‐induced QT interval prolongation, indicating that halothane anaesthesia can reduce the repolarization reserve of the heart in vivo.

British Journal of Pharmacology (2005) 146, 561–567. doi:10.1038/sj.bjp.0706352
The role of epithelial P2Y2 and P2Y4 receptors in the regulation of intestinal chloride secretion
Authors: Ghanem Esam , Robaye Bernard , Leal Teresinha , Leipziger Jens , Driessche Willy Van , Beauwens Renaud , Boeynaems Jean‐Marie
Published: August 2005

UTP‐induced chloride secretion by the intestinal mucosa mounted in Ussing chambers was assessed by measurement of the short‐circuit current (Isc) in the presence of phloridzin in the case of jejunum or amiloride in the case of colon to eliminate any contribution of electrogenic Na+ movement to the net ionic transport. Since we have previously demonstrated the absence of chloride‐secretory response to apical UTP in the jejunum from P2Y4‐null mice, in the present study we studied the response to basolateral UTP in the jejunum and to either apical or basolateral UTP in the colon, in both P2Y2‐ and P2Y4‐deficient mice.

In the jejunum, the chloride‐secretory response to basolateral UTP was partially reduced in both P2Y2‐ (40%) and P2Y4‐ (60%) null mice.

In the colon, both apical or basolateral UTP increased the Isc. That response was abolished in a chloride‐free medium.

The colonic chloride‐secretory response to either basolateral or apical UTP was abolished in P2Y4‐deficient mice, but not significantly affected in P2Y2‐deficient mice. The chloride‐secretory response to forskolin was potentiated by prior basolateral addition of UTP and this potentiation was abolished in P2Y4‐null mice.

The jejunum of mice homozygous for the ΔF508 mutation of cystic fibrosis transmembrane conductance regulator was responsive to UTP, but the magnitude of that response was smaller than in the wild‐type littermates.

In conclusion, the P2Y4 receptor fully mediates the chloride‐secretory response to UTP in both small and large intestines, except at the basolateral side of the jejunum, where both P2Y2 and P2Y4 receptors are involved.

British Journal of Pharmacology (2005) 146, 364–369. doi:10.1038/sj.bjp.0706353
Chronic nitroglycerine administration reduces endothelial nitric oxide production in rabbit mesenteric resistance artery
Authors: Yamamoto Tamao , Kajikuri Junko , Watanabe Yoshimasa , Suzuki Yoshikatsu , Suzumori Kaoru , Itoh Takeo
Published: August 2005

We investigated whether 10 days' in vivo treatment with nitroglycerine (NTG) would inhibit nitric oxide production by the endothelial cells of resistance arteries ex vivo and, if so, what the underlying mechanism might be.

ACh increased the intracellular nitric oxide concentration ([NO]i; estimated using the nitric oxide‐sensitive fluorescent dye diaminofluorescein‐2) within the endothelial cells of rabbit mesenteric resistance arteries. This effect was significantly smaller in arteries isolated from NTG‐treated rabbits than in those from control rabbits. The reduction in endothelial [NO]i in NTG‐treated rabbits was prevented when olmesartan (blocker of type 1 angiotensin II receptors (AT1Rs)) was coadministered in vivo with NTG and also when the superoxide scavenger manganese (III) tetrakis‐(4‐benzoic acid) porphyrin (Mn‐TBAP), the protein kinase C (PKC) inhibitor GF109203X or L‐arginine (with or without the active form of folate (5‐methyltetrahydrofolate)) was incubated with the arteries in vitro.

Endothelial cell superoxide production (estimated by ethidium fluorescence) was greatly increased in arteries from NTG‐treated rabbits. This was normalized by in vivo coadministration of olmesartan with NTG and also by in vitro application of Mn‐TBAP or GF109203X (but not of 5‐methyltetrahydrofolate+L‐arginine).

ACh increased the intracellular Ca2+ concentration (estimated using the Ca2+‐sensitive dye Fura 2) within endothelial cells, the increase being not significantly different between NTG‐treated rabbits and control rabbits.

We conclude that in NTG‐treated rabbits, endothelial nitric oxide production in mesenteric resistance arteries is reduced, possibly through a reduction in the bioavailability of L‐arginine via an action mediated by superoxide. Activation of the AT1R–PKC pathway may be involved in increasing superoxide production.

British Journal of Pharmacology (2005) 146, 534–542. doi:10.1038/sj.bjp.0706365
Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA–peptide tetramers
Authors: Cobbold Mark , Khan Naeem , Pourgheysari Batoul , Tauro Sudhir , McDonald Dorothy , Osman Husam , Assenmacher Mario , Billingham Lucinda , Steward Colin , Crawley Charles , Olavarria Eduardo , Goldman John , Chakraverty Ronjon , Mahendra Premini , Craddock Charles , Moss Paul A.H.
Published: August 2005

Stem cell transplantation is used widely in the management of a range of diseases of the hemopoietic system. Patients are immunosuppressed profoundly in the early posttransplant period, and reactivation of cytomegalovirus (CMV) remains a significant cause of morbidity and mortality. Adoptive transfer of donor-derived CMV-specific CD8+ T cell clones has been shown to reduce the rate of viral reactivation; however, the complexity of this approach severely limits its clinical application. We have purified CMV-specific CD8+ T cells from the blood of stem cell transplant donors using staining with HLA–peptide tetramers followed by selection with magnetic beads. CMV-specific CD8+ cells were infused directly into nine patients within 4 h of selection. Median cell dosage was 8.6 × 103/kg with a purity of 98% of all T cells. CMV-specific CD8+ T cells became detectable in all patients within 10 d of infusion, and TCR clonotype analysis showed persistence of infused cells in two patients studied. CMV viremia was reduced in every case and eight patients cleared the infection, including one patient who had a prolonged history of CMV infection that was refractory to antiviral therapy. This novel approach to adoptive transfer has considerable potential for antigen-specific T cell therapy.
Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs
Authors: Yoneyama Hiroyuki , Matsuno Kenjiro , Toda Etsuko , Nishiwaki Tetsu , Matsuo Naoki , Nakano Akiko , Narumi Shosaku , Lu Bao , Gerard Craig , Ishikawa Sho , Matsushima Kouji
Published: August 2005

Antiviral cell–mediated immunity is initiated by the dendritic cell (DC) network in lymph nodes (LNs). Plasmacytoid DCs (pDCs) are known to migrate to inflamed LNs and produce interferon (IFN)-α, but their other roles in antiviral T cell immunity are unclear. We report that LN-recruited pDCs are activated to create local immune fields that generate antiviral cytotoxic T lymphocytes (CTLs) in association with LNDCs, in a model of cutaneous herpes simplex virus (HSV) infection. Although pDCs alone failed to induce CTLs, in vivo depletion of pDCs impaired CTL-mediated virus eradication. LNDCs from pDC-depleted mice showed impaired cluster formation with T cells and antigen presentation to prime CTLs. Transferring circulating pDC precursors from wild-type, but not CXCR3-deficient, mice to pDC-depleted mice restored CTL induction by impaired LNDCs. In vitro co-culture experiments revealed that pDCs provided help signals that recovered impaired LNDCs in a CD2- and CD40L-dependent manner. pDC-derived IFN-α further stimulated the recovered LNDCs to induce CTLs. Therefore, the help provided by pDCs for LNDCs in primary immune responses seems to be pivotal to optimally inducing anti-HSV CTLs.
CD28 costimulatory signal induces protein arginine methylation in T cells
Authors: Blanchet Fabien , Cardona Ana , Letimier Fabrice A. , Hershfield Michael S. , Acuto Oreste
Published: August 2005

Protein phosphorylation initiates signal transduction that triggers lymphocyte activation. However, other posttranslational modifications may contribute to this process. Here, we show that CD28 engagement induced protein arginine methyltransferase activity and methylation on arginine of several proteins, including Vav1. Methylation of Vav1 and IL-2 production were reduced by inhibiting S-adenosyl-L-homocysteine hydrolase, an enzyme that regulates cellular transmethylation. Methylated Vav1 was induced in human and mouse T cells and selectively localized in the nucleus, which suggested that this form marks a nuclear function of Vav1. Our findings uncover a signaling pathway that is controlled by CD28 that is likely to be important for T cell activation.