bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualizing astrophysical N-body systems
Authors: Dubinski John
Published: December 2008

I begin with a brief history ofN-body simulation and visualization and then go on to describe various methods for creating images and animations of modern simulations in cosmology and galactic dynamics. These techniques are incorporated into a specialized particle visualization software library called MYRIAD that is designed to render images within large parallelN-body simulations as they run. I present several case studies that explore the application of these methods to animations in star clusters, interacting galaxies and cosmological structure formation.
Statistical catch-at-age analysis vs. ADAPT-VPA: the case of Gulf of Maine cod
Authors: Butterworth Doug S. , Rademeyer Rebecca A.
Published: December 2008

Butterworth, D. S., and Rademeyer, R. A. 2008. Statistical catch-at-age analysis vs. ADAPT-VPA: the case of Gulf of Maine cod. – ICES Journal of Marine Science, 65: 1717–1732. In 2003, given an estimate of a spawning-stock biomass (Bsp) of 27% of the maximum sustainable yield (MSY) level based on an adaptive framework-virtual population analysis (ADAPT-VPA) assessment using data only after 1981, the Gulf of Maine cod (Gadus morhua) stock was deemed “overfished” under the US Magnuson–Stevens Act. However, an alternative statistical catch-at-age assessment (SCAA) at the time, using survey data from 1964, indicated Bsp above . This is investigated, together with other (sometimes conflicting) suggestions made during a number of recent assessment reviews of this stock. The primary reason for the different result is that the ADAPT-VPA assessment imposed asymptotically flat selectivity-at-age when there was strong statistical evidence for dome-shaped selectivity. Once adjusted for this, either assessment method robustly estimates Bsp relatively close to rather than below the “overfished” threshold of 0.5 . SCAA allows the longer series of survey data available to be incorporated, providing a better basis to estimate MSY-related targets and doubling the related precision in some cases. As such targets are important when implementing the Magnuson–Stevens Act, SCAA seems preferable to ADAPT-VPA for assessing this stock. Some broader inferences to be drawn from this comparative process include the need for: (i) careful treatment of the plus-group, especially if selectivity may be dome-shaped; (ii) flexible parameterizations of selectivity-at-age in SCAA to avoid false perceptions of the precision of results; and (iii) care in the use of the Beverton–Holt stock–recruitment function, as it gives inappropriately low estimates of if there is an overall negative trend in the estimates of recruitment plotted against Bsp.
The use of species-specific TaqMan probes for identifying early stage gadoid eggs following formaldehyde fixation
Authors: Goodsir Freya , Armstrong Michael J. , Witthames Peter R. , Maxwell David L. , Fox Clive J.
Published: December 2008

Goodsir, F., Armstrong, M. J., Witthames, P. R., Maxwell, D. L., and Fox, C. J. 2008. The use of species-specific TaqMan probes for identifying early stage gadoid eggs following formaldehyde fixation. – ICES Journal of Marine Science, 65: 1573–1577. Surveys of fish eggs are increasingly being used to monitor the spawning areas and stock status of commercially important species such as Atlantic cod (Gadus morhua), but early stage cod eggs are visually indistinguishable from those of several other common co-occurring species, including haddock (Melanogrammus aeglefinus) and whiting (Merlangius merlangus). In recent surveys in the Irish and North Seas, a molecular identification technique (TaqMan multiplex real-time polymerase chain-reaction) assay has been used to overcome this problem. The method needs high-quality DNA, so the current protocol requires that individual “cod-like” eggs are “presorted” from plankton hauls on board ship and immediately preserved in ethanol. This increases seagoing staff costs, can be a difficult process at sea, and means that plankton sampling cannot be undertaken from non-specialized vessels such as fishing boats. Successful application of TaqMan probes to DNA from eggs preserved in formalin would overcome these problems, but previous attempts have resulted in poor success. In this study, batches of hatchery-sourced cod, haddock, and whiting eggs were fixed in 4% buffered formalin for up to 3 weeks, then transferred to a formaldehyde-free solution for 1, 2, or 3 months. After these periods they were assessed visually for fixation quality and analysed using species-specific TaqMan probes. Eggs, which had been fixed for up to 3 weeks in formalin, were identified successfully, although the positive rate (84–96%) was slightly lower than samples preserved throughout in ethanol (92–99%). There was no increase in the percentage of eggs misidentified comparing formalin-fixed and ethanol-preserved material. These results suggest that TaqMan probes can be applied successfully to fish eggs fixed in 4% buffered formalin for up to 3 weeks.
Has the fishery contributed to a major shift in the distribution of South African sardine?
Authors: Coetzee Janet C. , van der Lingen Carl D. , Hutchings Laurence , Fairweather Tracey P.
Published: December 2008

Coetzee, J. C., van der Lingen, C. D., Hutchings, L., and Fairweather, T. P. 2008. Has the fishery contributed to a major shift in the distribution of South African sardine? – ICES Journal of Marine Science, 65: 1676–1688. A major shift in the distribution of South African sardine (Sardinops sagax) has resulted in a significant spatial mismatch in fishing effort vs. fish abundance in recent years. The sardine fishery started on the west coast during the 1940s, and processing capacity there increased rapidly. This trend together with increases in annual landings continued up to the early 1960s, but then the fishery collapsed as a consequence of overfishing. The population then recovered steadily during the 1980s and 1990s, coincident with, but perhaps not entirely attributable to, the inception of conservative management practices, to support catches similar to pre-collapse levels. Since 2001, however, most of the sardine population has been situated on South Africa’s south coast, far from processing facilities. Fishing effort has increased concomitantly on that coast, particularly during the past three years, reflecting the continued decline in the abundance of sardine on the west coast. Three hypotheses explaining the change in the distribution of sardine have been proposed: (i) intensely localized (i.e. west coast) fishing pressure depleted that part (or functionally distinct unit) of the population; (ii) the shift was environmentally induced; and (iii) successful spawning and recruit survival on the south coast contributed disproportionately more towards the bulk of recruitment, and progeny spawned there now dominate the population and exhibit natal homing. The first of these hypotheses is evaluated, and management implications of the shift discussed.
The role of fatty acid hydrolase gene variants in inflammatory bowel disease
Authors: STORR M. , EMMERDINGER D. , DIEGELMANN J. , YÜCE B. , PFENNIG S. , OCHSENKÜHN T. , GÖKE B. , LOHSE P. , BRAND S.
Published: December 2008

Background  Recent studies suggest a role for the endocannabinoid system, including fatty acid amide hydrolase (FAAH), in intestinal inflammation.

Aim  To analyse FAAH expression and the FAAH 385 C/A (p.Pro129Thr; rs324420) single nucleotide polymorphism (SNP) in‐patients with Crohn’s disease (CD) and ulcerative colitis (UC).

Patients and methods  Genomic DNA from 1008 individuals (CD: n = 435; UC: n = 167; controls: n = 406) was analysed for the FAAH 385 C/A SNP. We determined FAAH mRNA expression by quantitative PCR in CD and UC lesions as well as in intestinal epithelial cells (IECs).

Results  There were no significant differences regarding the frequency of this SNP in the three study groups (CD, UC, controls). However, CD patients homozygous for the FAAH p.Pro129Thr polymorphism were more likely to develop a severe disease phenotype associated with fistulas (P = 0.03, OR 3.12, 95% CI 1.08–8.98) and extra‐intestinal manifestations (P = 0.005, OR 4.29, CI 1.49–12.35). In UC, homozygous carriers had an earlier disease onset than wild‐type carriers (P = 0.01). FAAH mRNA expression correlated with IL‐8 mRNA expression in CD lesions (r = 0.53). However, pro‐inflammatory stimuli did not significantly increase FAAH mRNA expression in IECs.

Conclusion  The FAAH p.Pro129Thr polymorphism may modulate the CD phenotype.
Impact of the haplotypes of the human pregnane X receptor gene on the basal and St John's wort‐induced activity of cytochrome P450 3A4 enzyme
Authors: Wang Xue‐Ding , Li Jia‐Li , Su Qi‐Biao , Guan Su , Chen Jie , Du Jun , He Yu‐Wen , Zeng Jun , Zhang Jin‐Xin , Chen Xiao , Huang Min , Zhou Shu‐Feng
Published: December 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Human pregnane X receptor (PXR/NR1I2) is a key regulator of cytochrome P450 3A4.

• To date, there are 198 reported SNPs for the human PXR/NR1I2 gene.

• Some of these SNPs are found to affect the inducing ability of PXR to CYP3A4.

WHAT THIS STUDY ADDS

• This study, for the first time, has investigated the effect of PXR haplotype on basal and St John's wort‐induced CYP3A4 activity in humans.

• H1/H1 of the PXR gene had weaker basal transcriptional activity but greater inducible transcriptional activity to CYP3A4 than H1/H2 and H2/H2.

AIMS

Human pregnane X receptor (PXR/NR1I2) is the master regulator of CYP3A4, which metabolizes >50% of drugs on the market. This study investigated the relationship between the two most frequent haplotypes [H1 (TCAGGGGCCACC) and H2 (CCGAAAACTAAT)] of PXR and basal and St John's wort (SJW)‐induced CYP3A4 activity.

METHODS

Ten healthy subjects carrying H1 and H2 haplotypes (three subjects with H1/H1, four with H1/H2 and three with H2/H2) entered this study. The 10 subjects did not carry CYP3A4*4, *5 and *6. All subjects were administrated a 300‐mg SJW tablet three times daily for 14 days, and CYP3A4 activity was measured using nifedipine (NIF) as a probe. The plasma concentrations of NIF and dehydronifedipine (DNIF) were determined by a validated liquid chromatography/mass spectrometry/mass spectrometry method.

RESULTS

After administration of SJW, the AUC0–∞ of NIF decreased significantly, and the AUC0–∞ of DNIF increased significantly (P < 0.05). For H1/H2, the AUC0–∞ of NIF decreased by 42.4%, and the AUC0–∞ of DNIF increased by 20.2%; for H2/H2, the AUC0–∞ of NIF decreased by 47.9%, and the AUC0–∞ of DNIF increased by 33.0%; for H1/H1, the AUC0–∞ of NIF decreased by 29.0%, yet the AUC0–∞ of DNIF increased by 106.7%. The increase of the AUC0–∞ of DNIF in H1/H1 was significantly different from the other two haplotype pairs (P < 0.05). Meanwhile, before administration of SJW, the ratio of AUC0–∞(DNIF)/AUC0–∞(NIF) was the lowest for H1/H1 (22.1%), compared with H1/H2 (58.7%) and H2/H2 (30.0%).

CONCLUSIONS

H1/H1 of the human PXR gene had weaker basal transcriptional activity but greater inducible transcriptional activity to CYP3A4 than H1/H2 and H2/H2.
Brood conspicuousness and clutch viability in male‐caring assassin bugs (Rhinocoris tristis)
Authors: GILBERT JAMES , MANICA ANDREA
Published: December 2008

Abstract 1. Conspicuousness to mates can bring benefits to both males (increased mating success) and females (reduced search costs), but also brings costs (e.g. increased predation and parasitism). Assassin bugs, Rhinocoris tristis, lay egg clutches either on exposed stems or hidden under leaves. Males guard eggs against parasitoids. Guarding males are attractive to females who add subsequent clutches to the brood. This is an excellent opportunity to study the effects of conspicuousness on the fitness of males and females.

2. Using viable eggs in a multi‐clutch brood as a correlate of fitness, the present study examined whether laying eggs on stems affected (1) female fitness, through exposure to parasitism and cannibalism, and (2) male fitness, through attracting further females.

3. Stem broods were more parasitised. However, males on stems accumulated more mates and more eggs, a net benefit even accounting for parasitism. The eggs gained from being on a stem were cannibalised. By contrast, higher mortality on stems suggests that females should gain by ovipositing on leaves. To the extent that egg viability represents fitness, male and female interests may therefore differ. This suggests a potential for sexual conflict that may affect other species with male care.

4. Despite higher costs, females actually initiated more broods, and subsequently added bigger clutches to broods, on stems than under leaves. This suggests either that viable eggs do not reflect fitness, or that females laid in unfavourable locations. The key is now to address lifetime fitness, since unmeasured factors may affect offspring viability post‐hatching, and to investigate who controls the location of oviposition in R. tristis.
Trail pheromones of ants
Authors: DAVID MORGAN E.
Published: December 2008

AbstractThe study of trail laying, recruitment of workers and trail‐following by worker ants comprises a co‐operative study of entomologists and chemists that has resulted in the identification of the chemical nature of such pheromones in many species of five subfamilies of ants. These pheromones may comprise a single compound or, in one exceptional case, a blend of as many as 14 compounds, they may come from a single gland, or in some cases, a combination of two glands. They may be peculiar to a single species or may be shared by a number of species. They exist in the glandular secretion in nanogram to picogram quantities and are detected by workers in minute amounts on a trail. The present state of knowledge of these pheromones and their chemical structures is reviewed. Suitable bioassays and odour perception are discussed and the stereobiology of a few examples is considered.
Functional association of cell death suppressor, Arabidopsis Bax inhibitor‐1, with fatty acid 2‐hydroxylation through cytochrome b5
Authors: Nagano Minoru , Ihara‐Ohori Yuri , Imai Hiroyuki , Inada Noriko , Fujimoto Masaru , Tsutsumi Nobuhiro , Uchimiya Hirofumi , Kawai‐Yamada Maki
Published: December 2008

Bax inhibitor‐1 (BI‐1) is a widely conserved cytoprotective protein localized in the endoplasmic reticulum (ER) membrane. We identified Arabidopsis cytochrome b5 (AtCb5) as an interactor of Arabidopsis BI‐1 (AtBI‐1) by screening the Arabidopsis cDNA library with the split‐ubiquitin yeast two‐hybrid (suY2H) system. Cb5 is an electron transfer protein localized mainly in the ER membrane. In addition, a bimolecular fluorescence complementation (BiFC) assay and fluorescence resonance energy transfer (FRET) analysis confirmed that AtBI‐1 interacted with AtCb5 in plants. On the other hand, we found that the AtBI‐1‐mediated suppression of cell death in yeast requires Saccharomyces cerevisiae fatty acid hydroxylase 1 (ScFAH1), which had a Cb5‐like domain at the N terminus and interacted with AtBI‐1. ScFAH1 is a sphingolipid fatty acid 2‐hydroxylase localized in the ER membrane. In contrast, AtFAH1 and AtFAH2, which are functional ScFAH1 homologues in Arabidopsis, had no Cb5‐like domain, and instead interacted with AtCb5 in plants. These results suggest that AtBI‐1 interacts with AtFAHs via AtCb5 in plant cells. Furthermore, the overexpression of AtBI‐1 increased the level of 2‐hydroxy fatty acids in Arabidopsis, indicating that AtBI‐1 is involved in fatty acid 2‐hydroxylation.
High‐resolution mapping revealed a 1.3‐Mbp genomic inversion in Ssi1, a dominant semidwarf gene in rice (Oryza sativa)
Authors: Miura K. , Wu J. , Sunohara H. , Wu X. , Matsumoto T. , Matsuoka M. , Ashikari M. , Kitano H.
Published: December 2008

Dwarf or semidwarf characters are an important trait for crop breeding as they provide lodging resistance. The rice mutant line DMF‐1 has a dm‐type semidwarf phenotype and high‐lodging resistance controlled by the dominant gene, Short second internode 1 (Ssi1). To elucidate the mechanism of reducing culm length in DMF‐1, we sought to identify the Ssi1 gene by positional cloning using the chromosome segment substitution line as a crossing parent. As a result of high‐resolution mapping, we found a 1.3‐Mbp genomic inversion and a newly arranged gene in the Ssi1 locus. In this study, we report the high‐resolution mapping and physical mapping of Ssi1. We also discuss the possible function of a novel rearranged Ssi1 gene for the dominant dm‐type semidwarf phenotype.
Gatifloxacin‐based triple therapy as a third‐line regimen for Helicobacter pylori eradication
Authors: Nishizawa Toshihiro , Suzuki Hidekazu , Nakagawa Izumi , Iwasaki Eisuke , Masaoka Tatsuhiro , Hibi Toshifumi
Published: December 2008

Background and Aim:  This study was designed to investigate the efficacy of gatifloxacin (GAT)–based triple therapy as a third‐line treatment for Helicobacter pylori (H. pylori) eradication, according to the assessment of the susceptibility to GAT and gyrA mutation.

Methods:  Fourteen patients who had eradication failure following both clarithromycin‐based triple therapy and metronidazole‐based triple therapy, or who were infected with H. pylori isolates that were resistant to both clarithromycin and metronidazole after failure of clarithromycin‐based triple therapy, were enrolled. These patients were randomly assigned to two groups: (i) rabeprazole and amoxicillin (RA) and (ii) rabeprazole, amoxicillin, and GAT for 7 days (RAG). The minimal inhibitory concentrations were determined by the agar dilution method. The gyrA gene was examined by sequencing.

Results:  The eradication rate was 0% in the RA group and 75% in the RAG group. The eradication rate in the RAG group was 100% in patients infected with GAT‐susceptible bacteria and/or bacteria without gyrA mutations, but was only 33.3% in those infected with GAT‐resistant bacteria or bacteria with gyrA mutations.

Conclusion:  Although GAT may be a promising candidate for third‐line therapy, its selection must be based on the results of drug susceptibility testing or gyrA analyses.
Endoscopic survey of low‐dose‐aspirin‐induced gastroduodenal mucosal injuries in patients with ischemic heart disease
Authors: Nema Hiroaki , Kato Mototsugu , Katsurada Takehiko , Nozaki Youichi , Yotsukura Akihiko , Yoshida Izumi , Sato Katsuhiko , Kawai Yuko , Takagi Yasushi , Okusa Takanori , Takiguchi Shunichi , Sakurai Masayuki , Asaka Masahiro
Published: December 2008

Background and Aim:  Low‐dose aspirin is effective for the prevention of cardiovascular and cerebrovascular events, but the frequency of gastrointestinal injuries among users of low‐dose aspirin in Japan is currently unknown. In the present study endoscopic examination was performed to investigate the frequency of gastroduodenal injuries associated with low‐dose aspirin in patients with ischemic heart disease (IHD).

Methods:  Screening upper endoscopic examinations were prospectively performed on 131 patients with IHD who were not receiving antiulcer treatment. Endoscopic findings such as ulcers and flat erosions were assessed as mucosal injuries.

Results:  Mucosal injuries were found in 62 of 101 (61.4%) low‐dose aspirin users and three of 30 (10%) nonaspirin users. There were significantly more mucosal injuries among low‐dose aspirin users than among the non‐users (P < 0.0001). Gastroduodenal ulcers were found in 19 of 101 (18.8%) low‐dose aspirin users compared with one of 30 (3.3%) nonaspirin users. The frequency of mucosal injuries was not associated with the duration of aspirin treatment.

Conclusion:  Endoscopy frequently reveals low‐dose aspirin‐induced gastroduodenal injuries in patients with IHD.
Correlations among total colonoscopic findings, clinical symptoms, and laboratory markers in ulcerative colitis
Authors: Osada Taro , Ohkusa Toshifumi , Okayasu Isao , Yoshida Tsutomu , Hirai Shu , Beppu Kazuko , Shibuya Tomoyoshi , Sakamoto Naoto , Kobayashi Osamu , Nagahara Akihito , Terai Takeshi , Watanabe Sumio
Published: December 2008

Background and Aim:  Colonoscopy plays an integral role in the diagnosis, management and surveillance of ulcerative colitis (UC). In the present study we assessed the relationship between endoscopic and histological findings, clinical symptoms, and laboratory data.

Methods:  We performed total colonoscopy examinations in 54 consecutive patients with UC. Seven segments (appendiceal region, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum) were scored for endoscopic and histological activity. The patients were also evaluated using a symptom‐activity index and laboratory markers: C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell (WBC) and platelet (plt) counts.

Results:  There was a significant positive correlation between endoscopic and histological scores (rs = 0.738), and between symptom activity score, endoscopic score (rs = 0.444), and histological score (rs = 0.557). Although the endoscopic and histological scores of distal colonic lesions (rectum–sigmoid, endoscopic: rs = 0.515, histological: rs = 0.624) correlated with clinical symptoms, there was no similar correlation for the proximal colon (appendiceal region–descending; endoscopic, rs = 0.268, histological, rs = 0.329). CRP, ESR, and WBC count also correlated with the sum of endoscopic and histological scores (CRP, rs = 0.447, rs = 0.369; ESR, rs = 0.483, rs = 0.589; WBC, rs = 0.338, rs = 0.330), whereas platelet count did not (rs = 0.171, rs = 0.210). In partciular, CRP and ESR were well correlated with the activity of proximal colonic lesions (CRP, rs = 0.474, rs = 0.480; ESR, rs = 0.423, rs = 0.529) rather than with that of distal lesions (CRP, rs = 0.236, rs = 0.212; ESR, rs = 0.368, rs = 0.497).

Conclusions:  In this study, clinical symptoms reflected the activity of distal colonic lesions, whereas CRP and ESR reflected the activity of proximal lesions. Therefore, total colonoscopy may be indicated when CRP or ESR is elevated in UC patients in clinical remission.
Relationships between Helicobacter pylori infection status, endoscopic, histopathological findings, and cytokine production in the duodenum of Crohn's disease patients
Authors: Ando Takafumi , Watanabe Osamu , Ishiguro Kazuhiro , Maeda Osamu , Ishikawa Daisuke , Minami Masaaki , Hasegawa Motofusa , Kondo Shinya , Goto Yasuyuki , Ohmiya Naoki , Niwa Yasumasa , Goto Hidemi
Published: December 2008

Background:  The chronic inflammatory process in patients with Crohn's disease (CD) may affect any part of the gastrointestinal (GI) tract. The pathogenesis of CD involves immunological abnormalities, including deficient or excessive expression of cytokines. We examined Helicobacter pylori infection status, endoscopic and histopathological findings, and cytokine production in the duodenum of CD patients in comparison with controls.

Methods:  Thirty‐eight CD patients underwent diagnostic upper GI endoscopy. Twelve age‐ and sex‐matched health checkup examinees were used as controls. H. pylori infection status was assessed by the 13C‐urea breath test. At the time of endoscopy, two biopsy specimens each were obtained from the second portion of the duodenum, one for hematoxylin‐eosin staining and immunohistochemical analysis with anti‐CD68 antibody, and one for in vitro organ culture. Interleukin (IL)‐6 and ‐8 levels were measured in organ culture supernatant by enzyme‐linked immunosorbent assay.

Results:  H. pylori infection was significantly (P < 0.05) more frequent in controls (42%) than in CD patients (8%). In the duodenum, erosions or ulcers were more frequent in CD patients (53%) than in controls (8%). Mononuclear cell infiltration in the duodenum was more severe in CD patients than in controls and IL‐6 production was higher, whereas IL‐8 production showed no significant difference. CD68+ cells in the duodenum were more prominent in CD patients than in controls.

Conclusions:  H. pylori infection is unlikely in CD patients, but they show immunological abnormalities in the duodenum, possibly from innate immune responses.
Identification of the expression profile of apoptotic esophageal cancer cells by adenoviral‐fragile histidine triad treatment
Authors: Mimori Koshi , Ishii Hideshi , Inoue Hiroshi , Barnard Graham F , Mori Masaki
Published: December 2008

Background:  The fragile histidine triad (FHIT) functions as a tumor suppressor, and giving adenoviral‐FHIT (Ad‐FHIT) is thus expected to be clinically beneficial. Much attention has recently been focused on which genes are commonly regulated by Ad‐FHIT, and which genes are dominant in Ad‐FHIT‐induced apoptotic cells.

Methods:  Ad‐FHIT apoptosis‐induced cells (H1299 and TE4) and non‐apoptosis‐induced cells (TE2) were used in the current experiments. The total RNA extracted from Ad‐FHIT or control was labeled with Cy3‐dCTP or Cy5‐dCTP and hybridized with 19 192 genes on a chip. A microarray analysis for each gene was carried out with high reproducibility provided by seven independent experiments and duplicated oligos on a chip.

Results:  We listed the upregulated genes based on the TE4:TE2 expression ratio, such as c‐Src, Jak‐1, and sialyltransferase, which are expected to be target pathways as well as the downregulated genes, including CASP8 and CASP10, after Ad‐FHIT treatment in esophageal cancer.

Conclusions:  The current microarray analysis indicated that the apoptosis of esophageal cancer observed after giving Ad‐FHIT was possibly induced by activation of the c‐Src gene and inactivation of the CASP8 gene.
Increased intestinal expression of heme oxygenase‐1 and its localization in patients with ulcerative colitis
Authors: Takagi Tomohisa , Naito Yuji , Mizushima Katsura , Nukigi Yayoi , Okada Hitomi , Suzuki Takahiro , Hirata Ikuhiro , Omatsu Tatsushi , Okayama Tetsuya , Handa Osamu , Kokura Satoshi , Ichikawa Hiroshi , Yoshikawa Toshikazu
Published: December 2008

Background:  Heme oxygenase‐1 (HO‐1) is regarded as a sensitive and reliable indicator of cellular oxidative stress. Two end products of heme degradation, carbon monoxide (CO) and bilirubin, are involved in the protective role of HO‐1 against oxidative injury. We have demonstrated enhanced expression of this enzyme and increased concentration of CO in experimental models of colitis, but the role of HO‐1 in patients with ulcerative colitis (UC) has not been extensively investigated. The aim of the present study was to determine the intestinal levels and localization of ho‐1 mRNA and HO‐1 protein in patients with UC.

Methods:  Eighteen patients with UC and 13 patients with colon cancer were prospectively selected from subjects who underwent colonoscopy. Biopsy specimens were obtained from the inflamed mucosa of UC patients and from the normal mucosa at least 5 cm from the margin of carcinoma. The expression of ho‐1 mRNA was assayed by real‐time polymerase chain reaction (PCR). The colonic expression of HO‐1 was determined by immunohistochemistry and western blotting using a monoclonal antibody against HO‐1.

Results:  The expression of ho‐1 mRNA and HO‐1 protein was significantly increased in the colonic mucosa of patients with active UC compared with normal mucosa. In the patients with active UC, mononuclear cells in the submucosa of the colon were positive for HO‐1, and there was negligible staining in the epithelial cells.

Conclusion:  The present findings are evidence of the induction of HO‐1 in the colon of UC patients.
Microcirculatory alteration in low‐grade gastric mucosa‐associated lymphoma by Helicobacter heilmannii infection: Its relation to vascular endothelial growth factor and cyclooxygenase‐2
Authors: Nakamura Masahiko , Takahashi Shinichi , Matsui Hidenori , Murayama Somay Yamagata , Aikawa Chihiro , Sekiya Yukie , Nishikawa Kaori , Matsumoto Tsukasa , Yamada Haruki , Tsuchimoto Kanji
Published: December 2008

Background:  There are clinical reports that Helicobacter heilmannii, as well as Helicobacter pylori, has been clinically reported to cause gastric low‐grade mucosa‐associated lymphoid tissue‐type (MALT) lymphoma, although its precise mechanism remains to be clarified. Thus, the present study was undertaken to elucidate the alteration of the microcirculatory structure and the relation to angiogenetic factors in mice infected with H. heilmannii for 3 and 6 months.

Methods:  Immunohistochemical studies have been performed by FITC‐dextran intra‐aortic infusion or CD31, vascular endothelial growth factor‐A, cyclooxygenase 2 antibodies using our recently established model of gastric mucosa‐associated lymphoid tissue‐type gastric B‐cell lymphoma in C57BL/6 mice.

Results:  Increased microcirculatory network was recognized surrounding the MALT lymphoma tissues by both the FITC‐dextran infusion method and CD31 immunoreactivity. Vascular endothelial growth factor‐A immunoreactivity was recognized within the lymphoma tissues as well as in the marginal area, while cyclooxygense‐2 immunoreactivity was localized in the area surrounding the MALT lymphoma tissues.

Conclusion:  Increased microvascular network as well as enhanced VEGF‐A immunoreactivity was shown to be related to expansion of the MALT lymphoma formed by Helicobacter heilmannii infection.
Protective effect of sulfhydryl‐containing antioxidants against ischemia/reperfusion injury of prepubertal rat intestine
Authors: Tunc Turan , Öter Sükrü , Güven Ahmet , Topal Turgut , Kul Mustafa , Korkmaz Ahmet , Öngürü Önder , Sarici Ümit
Published: December 2008

Background and Aim:  Reactive oxygen species generated during reperfusion of the tissue are known to play an important role in the basic pathophysiology of ischemia/reperfusion (I/R) injury. The aim of this study was to investigate and compare the protective effects of three sulfide‐based antioxidants, N‐acetylcysteine (NAC), erdosteine (ERD), and α‐lipoic acid (LA), on I/R injury of the small intestine tissue.

Methods:  Forty male Sprague–Dawley rats weighing between 100–150 g were divided into five groups (n = 8 for each): control (sham operated), I/R, I/R + NAC, I/R + ERD, and I/R + LA. Intestinal ischemia was provided by occluding the superior mesenteric artery via a special microvascular clamp; ischemia for 30 min and reperfusion for 3 days were carried out. Ileal specimens were obtained to determine the tissue levels of malondialdehyde (MDA), protein carbonyl contents (PCO), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and histological changes.

Results:  The rats subjected to intestinal I/R exhibited an increase in tissue MDA and PCO; the levels could hardly be ameliorated in the treatment groups. SOD and GPx activities were significantly decreased in the I/R group, whereas their reduction was less expressed in the treatment groups. Additionally, the histopathological injury scores of the disulfide‐treated groups were lower than those of the I/R group.

Conclusion:  All of the sulfhydryl‐containing antioxidants used in this study exhibited a significant role in attenuating intestinal I/R injury; however, the outcome of the LA‐treated group was significantly marked than that of the others.
Comparison of double‐layered and covered Niti‐S stents for palliation of malignant dysphagia
Authors: Kim Eun Soo , Jeon Seong Woo , Park Soo Young , Cho Chang Min , Tak Won Young , Kweon Young Oh , Kim Sung Kook , Choi Yong Hwan
Published: December 2008

Background and Aim:  Covered metal stents have been accepted as the treatment of choice for malignant dysphagia caused by esophageal and gastric cardia cancer, but stent migration is a major shortcoming. A double‐layered Niti‐S stent was therefore introduced to obviate this problem. We aimed to compare double‐layered and covered Niti‐S stents regarding safety, efficacy, and feasibility in the treatment of malignant dysphagia.

Methods:  Thirty‐seven consecutive patients with malignant dysphagia due to inoperable esophageal or gastric cardia cancer were enrolled in a prospective, randomized study. The main outcomes were technical success, improvement in dysphagia score after stent insertion, and complications.

Results:  Technical success was achieved at a similar rate in both groups (covered, 19/19 [100%]vs double layered, 16/17 [94%]). A week after stent insertion, the mean dysphagia score improved significantly in the covered and double‐layered groups compared to baseline (from 2.95 ± 0.52 and 2.88 ± 0.33 to 1.00 ± 0.47 and 1.06 ± 0.24, respectively; P < 0.001). There was no difference in the survival of the patients in the two groups. The overall complications, including stent migration and tumor overgrowth, occurred more frequently with covered stents (11/19 [58%]) than double‐layered stents (2/17 [12%]; P = 0.006).

Conclusion:  Newly‐developed, self‐expanding metal stents, (covered and double‐layered Niti‐S stents) were equally effective and feasible treatments for malignant dysphagia. However, double‐layered Niti‐S stents are preferable due to their favorable safety profile.
Effects of uroguanylin on natriuresis in experimental nephrotic rats
Authors: BABA AKIKO , FUJIMOTO SHOUICHI , KIKUCHI MASAO , KITA TOSHIHIRO , KITAMURA KAZUO
Published: December 2008

Aim:  Uroguanylin, isolated from human and opossum urine, is a candidate intestinal natriuretic hormone that controls the sodium and water balance between the intestine and the kidneys. Levels of immunoreactive (ir)‐uroguanylin in the plasma and urine are increased in rats and humans with nephrotic syndrome, which is physiologically characterized by sodium retention with massive proteinuria. The present study evaluates the effect of natriuresis induced by uroguanylin on nephrotic rats.

Methods:  Normal rats and rats rendered nephrotic by injections of puromycin aminonucleoside (PAN) were treated with uroguanylin (0.5 nmol/h, delivered by an osmotic pump) or with vehicle during the sodium retention phase. All rats consumed the same quantity of sodium.

Results:  Uroguanylin did not increase urinary excretion of sodium and water in normal rats, but significantly increased urinary sodium excretion during the sodium retention phase in nephrotic rats (untreated vs uroguanylin‐treated nephrotic rats in mmol/mmol creatinine; 2.92 ± 0.65 vs 8.93 ± 2.53 on day 6, P < 0.05; 3.55 ± 0.47 vs 10.37 ± 1.73 on day 7, P < 0.01; 14.88 ± 2.32 vs 24.47 ± 2.86 on day 8, P < 0.05). Plasma levels of ir‐uroguanylin in uroguanylin‐treated nephrotic rats on day 6 were significantly increased compared with those in uroguanylin‐treated control and untreated nephrotic rats.

Conclusion:  Uroguanylin increased urinary sodium excretion in rats with PAN‐induced nephrosis, and might be useful for treating sodium retention in patients with nephrotic syndrome.
Effects of a 10‐week weight control program on obese patients with schizophrenia or schizoaffective disorder: A 12‐month follow up
Authors: Chen Chih‐Ken , Chen Yi‐Chih , Huang Yu‐Shu
Published: December 2008

Aims:  Weight gain secondary to antipsychotic medication is associated with many serious conditions, including type II diabetes mellitus, hypertension, and coronary heart disease, and also with poor medication compliance. Weight control programs may be of benefit to outpatients with schizophrenia, but also raise an issue of cost‐effectiveness. We aimed to evaluate the effectiveness of a 10‐week weight control program for outpatients taking atypical antipsychotics for treatment of schizophrenia, and to follow up the effects of this weight control program in controlling weight gain after termination of the program.

Methods:  A total of 33 patients with schizophrenia and antipsychotic‐related obesity were enrolled in a 10‐week multimodal weight control program. The patients' weights were recorded at baseline, week 4, week 8, week 10 (end of the intervention), week 12, week 24, and week 48. Secondary measures included blood sugar levels, cholesterol levels, triglyceride levels, quality of life and mental health.

Results:  For those who completed the weight control program, there was a mean weight loss of 2.1 kg by the end of the intervention, 3.7 kg over 6 months, and 2.7 kg over 12 months. The mean body mass index decreased by 0.8, 1.5 and 1.1 at week 10, week 24 and week 48, respectively, all with statistical significance.

Conclusions:  The 10‐week weight control program was effective in terms of weight reduction among obese patients with schizophrenia or schizoaffective disorder, and the weight reduction effect lasted for up to 6 months, and up to 12 months in some cases.
Neuropathy is associated with depression independently of health‐related quality of life in Japanese patients with diabetes
Authors: Yoshida Sumiko , Hirai Masashi , Suzuki Susumu , Awata Shuichi , Oka Yoshitomo
Published: December 2008

Objectives:  To identify factors independently associated with depression in Japanese patients with diabetes, after controlling for potential confounding factors.

Methods:  Among 197 outpatients with diabetes, 129 (type 1: 24, type 2: 105) completed a questionnaire concerning socio‐demographic and health‐related variables. Depression screening was done using Zung's Self‐Rating Depression Scale test, followed by diagnostic interviews by experienced psychiatrists employing the Diagnostic Statistical Manual of Mental Disorders, 4th edition (DSM‐IV).

Results:  Forty‐seven patients (36.4%) had symptomatological depression. A Self‐Rating Depression Scale cut‐off score of 40 had good sensitivity (100%) and modest specificity (59%) for detecting major depressive episode, in accordance with the DSM‐IV. Diabetic patients suffering from depression were more likely to have neuropathy, retinopathy, body pain, a feeling of poor general health, and lack of social support, than the non‐depressed patients. However, age, gender, marital status, diabetes type, insulin requirement, duration of diabetes, hemoglobin A1c (HbA1c) and the presence of nephropathy did not differ between the two groups. In multivariate logistic regression analysis, body pain (OR 3.26, 95% CI 1.31–8.08) and the presence of microvascular complications (OR 2.81, 95% CI 1.13–6.98) were independent factors associated with depression. Specifically, diabetic neuropathy (OR 3.10, 95% CI 1.17–8.22) was associated with depression independently of age, gender, marital status, social supports, quality of life, diabetes type, duration of diabetes, HbA1c, and insulin requirement.

Conclusions:  A diabetic complication, specifically neuropathy, was independently associated with depression in patients with diabetes. The present findings indicate the need to find a biological base common to both depression in diabetes and diabetic neuropathy.
Health service utilization in patients with major depression and co‐morbid pain
Authors: Alvarenga Marlies E , Caniato Riccardo N , Mauritz Anika , Braun Anja , Aljeesh Yousef , Baune Bernhard T
Published: December 2008

Aims:  Patients with depression often have co‐morbid pain symptoms. However, rates of service utilization by psychiatric in‐patients with co‐morbid pain symptoms are unknown. The purpose of this study is to estimate whether patients with major depression and co‐morbid pain access medical treatment for their pain as much as their counterparts with psychiatric diagnoses other than major depression.

Methods:  A total of 103 patients (62 female; 41 male) were assessed for a diagnosis of major depression applying a psychiatric clinical interview followed by a self‐report pain questionnaire, which assessed physical pain in psychiatric patients.

Results:  Patients with major depression reported higher rates of pain symptoms in the past 6 and 12 months than their counterparts with a psychiatric diagnosis other than major depression. Analysis of variance showed that patients with depression were less likely to attend medical and specialist services for their pain symptoms than their counterparts. On the contrary, depressed patients with pain attended more frequently general in‐patient services than non‐depressed patients with pain.

Conclusions:  Patients with depression suffer high rates of pain symptoms, but are at higher risk of not accessing appropriate services suggesting inadequate service utilization. The results have implications for screening and health care delivery for psychiatric patients with pain.
The high wire act: a comparison of British transatlantic foreign policies in the Second World War and the war in Iraq, 2001–2003
Authors: Tate Simon
Published: December 2008

Drawing upon ideas from critical geopolitics, this paper compares the role that the British government plays within the contemporary transatlantic alliance with that played by Churchill's government during the Second World War. It argues that the Blair government's approach to foreign policy has parallels with Churchill's – that it should act as a bridge between the US and European governments. From this basis the paper reflects upon geopolitical change since 1945, re‐evaluating the reasons for foreign policy failures during the Iraq War. Belying the assumption that these were caused by Blair's failures at diplomacy, it argues that failure was the result of an outdated geopolitical strategy.
Metrics or Peer Review? Evaluating the 2001 UK Research Assessment Exercise in Political Science
Authors: Butler Linda , McAllister Ian
Published: December 2008

Evaluations of research quality in universities are now widely used in the advanced economies. The UK's Research Assessment Exercise (RAE) is the most highly developed of these research evaluations. This article uses the results from the 2001 RAE in political science to assess the utility of citations as a measure of outcome, relative to other possible indicators. The data come from the 4,400 submissions to the RAE political science panel. The 28,128 citations analysed relate not only to journal articles, but to all submitted publications – including authored and edited books and book chapters. The results show that citations are the most important predictor of the RAE outcome, followed by whether or not a department had a representative on the RAE panel. The results highlight the need to develop robust quantitative indicators to evaluate research quality which would obviate the need for a peer evaluation based on a large committee. Bibliometrics should form the main component of such a portfolio of quantitative indicators.
Metabolism of Antiepileptic Medication: Newborn to Elderly
Authors: Leppik Ilo E.
Published: December 2008

Summary:Epilepsy affects individuals of all ages. Regimens of antiepileptic drugs (AEDs) and side‐effect profiles differ for infants, children, adults, and the elderly. Thus, the epileptologist must be familiar with the specific changes of AED metabolism with age. In general, metabolic rates are fastest in children; therefore, AED half‐lives are shortest in this group. Rates of AED elimination are slowest in neonates, infants, and children. Thus, children need larger dosages, on a mg/kg basis, than adults. The usual phenytora (PHT) dosage in adults is 4–6 mg/kg per day, but children may need a dosage three to five times higher. On the other hand, the PHT dosages in the elderly may need to be 3–4 mg/kg per day to achieve therapeutic levels. Likewise, the half‐life of carbamazepine (CBZ) is shortest in children and the elderly. Profiles of metabolites may also be age‐specific, a difference of particular importance for valproate (VPA). The relative amount of VPA metabolized to 4‐ene is more than twofold less in adults than in children, which may explain the different profile of hepatotoxicity seen by age. The elderly may be more vulnerable to adverse effects of AEDs. Many elderly have neurologic deficits that may render them more vulnerable to neurotoxic effects such as ataxia and cognitive disturbances. Also, low serum albumin concentrations, which result in decreased binding, may mask high serum AED concentrations. The hyponatremia associated with CBZ may be a particular concern in the elderly. Gingival hyperplasia, a concern in children, may not be a problem in the elderly.
Hormones and Epilepsy Through the Lifetime
Authors: Morrell Martha J.
Published: December 2008

Summary:Hormones influence brain function from gestation throughout life and may affect the seizure threshold by altering neuronal excitability. Estrogen enhances and progesterone diminishes neuronal excitability experimentally, whereas testosterone and corticosteroids have less consistent effects. Hormonal effects in the CNS also depend on the region of brain in which the hormone acts. Sites of action for most steroid hormones include the hypothalamus and limbic cortex, providing a mechanism for modulating behavior and endocrine function. Seizure patterns may change at certain life stages, perhaps as a result of alterations in hormones. At puberty, epilepsy and benign rolandic epilepsy often remit, while juvenile myoclonic and photosensitive epilepsy may arise. Other types of epilepsy do not respond predictably to events in the reproductive life or to advancing age. In some women, fluctuations in hormones over the menstrual cycle appear to increase seizure vulnerability, probably reflecting changes in relative amounts of estrogen and progesterone. Seizure patterns can be altered, for better or worse, during pregnancy. Whether this reflects the effects of hormones or changes in levels of antiepileptic drugs is not resolved. More information is needed about changes in established epilepsy at menopause and in the elderly. Better understanding of endocrine effects on seizures over a lifetime should lead to more effective epilepsy therapies.
Effect of Extended‐Release Naltrexone (XR‐NTX) on Quality of Life in Alcohol‐Dependent Patients
Authors: Pettinati Helen M. , Gastfriend David R. , Dong Qunming , Kranzler Henry R. , O’Malley Stephanie S.
Published: December 2008

Background:  Extended‐release naltrexone (XR‐NTX) is a once‐a‐month injectable formulation for the treatment of alcohol dependence previously shown to reduce drinking and heavy drinking relative to placebo (Garbutt et al., 2005). A 24‐week, randomized, double‐blind, placebo‐controlled study established the efficacy and safety of XR‐NTX in this patient population. In this report, the effect of XR‐NTX on quality of life (QOL) was examined.

Methods:  Alcohol‐dependent patients were randomly assigned to receive XR‐NTX 380 mg (N = 205), XR‐NTX 190 mg (N = 210), or placebo (N = 209), combined with a standardized psychosocial intervention. QOL was assessed using the Medical Outcomes Study 36‐item short‐form health survey, administered at baseline and at 4‐week intervals during 24 weeks of treatment.

Results:  Compared with U.S. population norms, patients showed initial impairment in the health‐related QOL domains of mental health, social functioning, and problems with work or other daily activities due to emotional problems. Adherence to all 6 injections was 65% for XR‐NTX 190 mg, 63% for XR‐NTX 380 mg, and 64% for placebo. Generalized estimating equations analyses using an intention‐to‐treat sample revealed that XR‐NTX 380 mg was associated with significantly greater improvements from baseline in mental health (p = 0.0496), social functioning (p = 0.010), general health (p = 0.048), and physical functioning (p = 0.028), compared with placebo. Linear regression analyses revealed that reductions from baseline in drinking (percentage of drinking days and percentage of heavy drinking days in the last 30 days) were significantly (p < 0.05) correlated with improvements in quality of life.

Conclusion:  Extended‐release naltrexone 380 mg in combination with psychosocial intervention was associated with improvements in QOL, specifically in the domains of mental health, social functioning, general health, and physical functioning.