bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of IP-10/CXCL10 in the progression of pancreatitis-like injury in mice after murine retroviral infection
Authors: Kawauchi Yusuke , Suzuki Kenji , Watanabe Shiro , Yamagiwa Satoshi , Yoneyama Hiroyuki , Han Gi Dong , Palaniyandi Suresh S. , Veeraveedu Punniyakoti T. , Watanabe Kenichi , Kawachi Hiroshi , Okada Yoshiaki , Shimizu Fujio , Asakura Hitoshi , Aoyagi Yutaka , Narumi Shosaku
Published: July 2006

Exocrinopathy and pancreatitis-like injury were developed in C57BL/6 (B6) mice infected with LP-BM5 murine leukemia virus, which is known to induce murine acquired immunodeficiency syndrome (MAIDS). The role of chemokines, especially CXCL10/interferon (IFN)-γ-inducible protein 10 (IP-10), a chemokine to attract CXCR3+T helper 1-type CD4+T cells, has not been investigated thoroughly in the pathogenesis of pancreatitis. B6 mice were inoculated intraperitoneally with LP-BM5 and then injected every week with either an antibody against IP-10 or a control antibody. Eight weeks after infection, we analyzed the effect of IP-10 neutralization. Anti-IP-10 antibody treatment did not change the generalized lymphadenopathy and hepatosplenomegaly of mice with MAIDS. The treatment significantly reduced the number of IP-10- and CXCR3-positive cells in the mesenteric lymph nodes (mLNs) but not the phenotypes and gross numbers of cells. In contrast, IP-10 neutralization reduced the number of mononuclear cells infiltrating into the pancreas. Anti-IP-10 antibody treatment did not change the numbers of IFN-γ+and IL10+cells in the mLN but significantly reduced their numbers, especially IFN-γ+and IL-10+CD4+T cells and IFN-γ+Mac-1+cells, in the pancreas. IP-10 neutralization ameliorated the pancreatic lesions of mice with MAIDS probably by blocking the cellular infiltration of CD4+T cells and IFN-γ+Mac-1+cells into the pancreas at least at 8 wk after infection, suggesting that IP-10 and these cells might play a key role in the development of chronic autoimmune pancreatitis.
Exercise training improves renal excretory responses to acute volume expansion in rats with heart failure
Authors: Zheng Hong , Li Yi-Fan , Zucker Irving H. , Patel Kaushik P.
Published: July 2006

Experiments were performed to test the postulate that exercise training (ExT) improves the blunted renal excretory response to acute volume expansion (VE), in part, by normalizing the neural component of the volume reflex typically observed in chronic heart failure (HF). Diuretic and natriuretic responses to acute VE were examined in sedentary and ExT groups of rats with either HF or sham-operated controls. Experiments were performed in anesthetized (Inactin) rats 6 wk after coronary ligation surgery. Histological data indicated that there was a 34.9 ± 3.0% outer and 42.5 ± 3.2% inner infarct of the myocardium in the HF group. Sham rats had no observable damage to the myocardium. In sedentary rats with HF, VE produced a blunted diuresis (46% of sham) and natriuresis (35% of sham) compared with sham-operated control rats. However, acute VE-induced diuresis and natriuresis in ExT rats with HF were comparable to sham rats and significantly higher than sedentary HF rats. Renal denervation abolished the salutary effects of ExT on renal excretory response to acute VE in HF. Since glomerular filtration rates were not significantly different between the groups, renal hemodynamic changes may not account for the blunted renal responses in rats with HF. Additional experiments confirmed that renal sympathetic nerve activity responses to acute VE were blunted in sedentary HF rats; however, ExT normalized the renal sympathoinhibition in HF rats. These results confirm an impairment of neurally mediated excretory responses to acute VE in rats with HF. ExT restored the blunted excretory responses as well as the renal sympathoinhibitory response to acute VE in HF rats. Thus the beneficial effects of ExT on cardiovascular regulation in HF may be partly due to improvement of the neural component of volume reflex.
Quantitative trait locus on chromosome 20q13 for plasma levels of C-reactive protein in healthy whites: the HERITAGE Family Study
Authors: Lakka Timo A. , Rankinen Tuomo , Rice Treva , Leon Arthur S. , Rao D. C. , Skinner James S. , Bouchard Claude
Published: July 2006

C-reactive protein (CRP) is a sensitive marker of systemic low-grade inflammation. Increased plasma levels of CRP predict the risk of cardiovascular and metabolic diseases. Although genetic factors account for 30–40% of individual differences in plasma CRP levels, genomic regions contributing to CRP levels remain unknown. We performed a genome-wide linkage scan for plasma CRP levels in healthy whites from the HERITAGE Family Study. CRP was measured with a high-sensitivity assay. Multipoint linkage analyses were performed in 280 sibling pairs with 654 markers using regression and variance components-based methods. Data were adjusted for independent correlates of plasma CRP. We showed the strongest evidence of linkage for plasma CRP levels on chromosome 20q13. Markers which gave suggestive linkages in this region were D20S52 [logarithm of odds (LOD) score 3.18, P = 0.00006], D20S857 (LOD score 2.87, P = 0.00014), D20S869 (LOD score 2.75, P = 0.0002), D20S480 (LOD score 2.59, P = 0.0003), D20S501 (LOD score 2.55, P = 0.0003), D20S840 (LOD score 2.18, P = 0.0008), and D20S876 (LOD score 2.07, P = 0.001). We also detected suggestive linkage on chromosome 5p13 for marker D5S1470 (LOD score 2.23, P = 0.0007). Chromosome 20q13 may contribute to plasma CRP levels in healthy whites. This region contains genes that are important in the inflammatory process and may play a role in the development of chronic inflammatory diseases. The present findings may be useful in the ongoing effort to search for genes contributing to inflammation and to identify individuals at an increased risk of chronic inflammatory diseases.
Recognition of Breast Cancer Cells by CD8+ Cytotoxic T-Cell Clones Specific for NY-BR-1
Authors: Wang Wei , Epler Jennifer , Salazar Lupe G. , Riddell Stanley R.
Published: July 2006

Immunotherapy for breast cancer using cytotoxic T cells (CTL) is hindered by the lack of well-characterized breast cancer antigens that are expressed in most breast tumor cells and recognized by CD8+ CTL. A recently described breast tissue differentiation antigen, NY-BR-1, is expressed in >80% breast tumors and elicits a humoral response in a subset of breast cancer patients. To identify potential NY-BR-1 epitopes that are recognized by CTL, CD8+ T cells were stimulated in vitro with autologous dendritic cells pulsed with NY-BR-1 peptides that were predicted to bind to HLA-A2. In multiple normal female donors and breast cancer patients, specific CD8+ CTL responses were detected by enzyme-linked immunospot assay against several NY-BR-1 peptides after two cycles of stimulation. CD8+ CTL clones against three NY-BR-1 epitopes were isolated and recognized peptide-pulsed target cells with high avidity. T-cell clones specific for one of the NY-BR-1 epitopes (p904) also recognized breast tumor cells expressing NY-BR-1, NY-BR-1− cells transfected with a cDNA encoding the NY-BR-1 protein, and autologous dendritic cells pulsed with opsonized NY-BR-1+ breast tumor cells. Taken together, these results show that the p904 epitope derived from NY-BR-1 is efficiently processed and presented endogenously and identify NY-BR-1 as a promising target for T-cell–based immunotherapy for breast cancer. (Cancer Res 2006; 66(13): 6826-33)
CD80 in Immune Suppression by Mouse Ovarian Carcinoma–Associated Gr-1+CD11b+ Myeloid Cells
Authors: Yang Rongcun , Cai Zhong , Zhang Yuan , Yutzy William H. , Roby Katherine F. , Roden Richard B.S.
Published: July 2006

An elevated number of Gr-1+CD11b+ myeloid cells has been described in mice bearing transplantable tumors, and has been associated with immune suppression. We examined the role of such myeloid suppressor cells in mice bearing the spontaneously transformed syngeneic mouse ovarian surface epithelial cell line, 1D8. We observed high levels of CD80 expression by Gr-1+CD11b+ cells from spleen, ascites, and tumor tissue of mice bearing 1D8 ovarian carcinoma, whereas CD40 and CD86 were absent. CD80 expression was not detected on Gr-1+CD11b+ cells from naïve mice. However, the expression of CD80 by Gr-1+CD11b+ cells from naïve mice was promoted by coculture with 1D8 cells. Because irradiated 1D8 cells, but not 1D8-conditioned medium, up-regulate CD80 expression by Gr-1+CD11b+ cells, this phenomenon likely requires direct interaction. Gr-1+CD11b+ cells derived from 1D8 tumor–bearing mice provided significant suppression of antigen-specific immune responses, but Gr-1+CD11b+ cells from naïve mice did not. Both short interfering RNA–mediated knockdown and genetic knockout of CD80 expression by Gr-1+CD11b+ cells of 1D8 tumor–bearing mice alleviated the suppression of antigen-specific immune responses. Suppression via CD80 on Gr-1+ CD11b+ myeloid cells was mediated by CD4+CD25+ T regulatory cells and required CD152. CD80 knockout or antibody blockade of either CD80 or CD152 retarded the growth of 1D8 tumor in mice, suggesting that expression of CD80 on Gr-1+CD11b+ myeloid cells triggered by 1D8 ovarian carcinoma suppresses antigen-specific immunity via CD152 signaling and CD4+CD25+ T regulatory cells. Thus, CD80-dependent responses to myeloid suppressor cells may contribute to tumor tolerance and the progression of ovarian carcinoma.(Cancer Res 2006; 66(13): 6807-15)
Pim-3, a Proto-Oncogene with Serine/Threonine Kinase Activity, Is Aberrantly Expressed in Human Pancreatic Cancer and Phosphorylates Bad to Block Bad-Mediated Apoptosis in Human Pancreatic Cancer Cell Lines
Authors: Li Ying-Yi , Popivanova Boryana K. , Nagai Yuichiro , Ishikura Hiroshi , Fujii Chifumi , Mukaida Naofumi
Published: July 2006

Pancreatic cancer still remains a serious health problem with <5% 5-year survival rate for all stages. To develop an effective treatment, it is necessary to identify a target molecule that is crucially involved in pancreatic tumor growth. We previously observed that Pim-3, a member of the proto-oncogene Pim family that expresses serine/threonine kinase activity, was aberrantly expressed in human and mouse hepatomas but not in normal liver. Here, we show that Pim-3 is also expressed in malignant lesions of the pancreas but not in normal pancreatic tissue. Moreover, Pim-3 mRNA and protein were constitutively expressed in all human pancreatic cancer cell lines that we examined and colocalized with the proapoptotic protein Bad. The ablation of endogenous Pim-3 by small hairpin RNA transfection promoted apoptosis, as evidenced by increases in a proportion of cells in the sub-G1 fraction of the cell cycle and in phosphatidyl serine externalization. A proapoptotic molecule, Bad, was phosphorylated constitutively at Ser112 but not Ser136 in human pancreatic cancer cell lines and this phosphorylation is presumed to represent its inactive form. Phosphorylation of Bad and the expression of an antiapoptotic molecule, Bcl-XL, were reduced by the ablation of endogenous Pim-3. Thus, we provide the first evidence that Pim-3 can inactivate Bad and maintain the expression of Bcl-XL and thus prevent apoptosis of human pancreatic cancer cells. This may contribute to the net increase in tumor volume or tumor growth in pancreatic cancer. (Cancer Res 2006; 66(13): 6741-7)
4-Nitroquinoline-1-Oxide Induces the Formation of Cellular Topoisomerase I-DNA Cleavage Complexes
Authors: Miao Ze-Hong , Rao V. Ashutosh , Agama Keli , Antony Smitha , Kohn Kurt W. , Pommier Yves
Published: July 2006

RecQ helicase BLM-deficient cells are characteristically hypersensitive to 4-nitroquinoline-1-oxide (4NQO). We recently reported that isogenic BLM-deficient cells (PNSG13) are more sensitive than BLM-complemented cells (PNSF5) to camptothecin, which specifically traps topoisomerase I cleavage complexes (Top1cc). We now report that PNSG13 are also 3.5-fold more sensitive to 4NQO compared with PNSF5 and that 4NQO induces higher levels of Top1cc and reduced histone γ-H2AX in PSNG13 than in PNSF5. Similarly, 4NQO induces more Top1cc in primary fibroblasts from a patient with Bloom syndrome than in normal human fibroblasts. 4NQO also induces Top1cc in colon cancer HCT116 and HT29 cells in a time- and concentration-dependent fashion. Of note, distinct from camptothecin, the Top1cc produced by 4NQO accumulate progressively after 4NQO addition and persist following 4NQO removal. The Top1cc induced by 4NQO are detectable by alkaline elution. To examine the functional relevance of the Top1cc induced by 4NQO, we used two stable topoisomerase I small interfering RNA (siRNA) cell lines derived from HCT116 and MCF7 cells. Both topoisomerase I siRNA cell lines are resistant to 4NQO, indicating that Top1cc contribute to the cellular activity of 4NQO. Collectively, these data show that 4NQO is an effective inducer of cellular Top1cc. Because 4NQO does not directly trap Top1cc in biochemical assays, we propose that active metabolites of 4NQO trap Top1cc by forming DNA adducts. Induction of Top1cc and histone γ-H2AX by 4NQO may contribute to the cellular effects of 4NQO, including its selective activity toward RecQ helicase BLM-deficient cells.(Cancer Res 2006; 66(13): 6540-5)
Epigenetic Silencing of the PTEN Gene in Melanoma
Authors: Mirmohammadsadegh Alireza , Marini Alessandra , Nambiar Sandeep , Hassan Mohamed , Tannapfel Andrea , Ruzicka Thomas , Hengge Ulrich R.
Published: July 2006

Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) seems to be an important tumor suppressor gene in melanoma. Because the PTEN gene is only infrequently deleted or mutated, and because the PTEN protein is low to absent in a significant number of melanomas, we investigated alternative methods of epigenetic silencing. We did quantitative positional methylation analysis (pyrosequencing) on 37 sera from melanoma patients and on 21 pairs of corresponding sera and melanoma specimens in addition to Taqman reverse transcription-PCR. We report significant positional PTEN promoter methylation in 62% of circulating DNA isolated from sera of patients with metastatic melanoma. The percentage of methylation of a selected CpG island in blood showed a correlation with methylation levels in the corresponding melanoma tissue. Moreover, high percentages of PTEN methylation were associated with low PTEN transcription levels. Using the demethylation agent 5-aza-2′-deoxycytidine, reduced methylation and a corresponding increase in PTEN protein were observed in BLM melanoma cells, leading to reduced AKT activity in an in vitro kinase assay. In summary, epigenetic PTEN silencing seems to be a relevant mechanism of inactivating this tumor suppressor gene in melanoma that may promote melanoma development by derepression of the AKT pathway. (Cancer Res 2006; 66(13); 6546-52)
The Primary Cilium in Cell Signaling and Cancer
Authors: Michaud Edward J. , Yoder Bradley K.
Published: July 2006

The primary cilium is a microtubule-based antenna-like structure that emanates from the surface of virtually all cells in the mammalian body. It is anchored to the cell by the basal body, which develops from the mother centriole of the centrosome in a manner that is coordinately regulated with the cell cycle. The primary cilium is a sensory organelle that receives both mechanical and chemical signals from other cells and the environment, and transmits these signals to the nucleus to elicit a cellular response. Recent studies revealed that multiple components of the Sonic hedgehog and platelet-derived growth factor receptor-α signal transduction pathways localize to the primary cilium, and that loss of the cilium blocks ligand-induced signaling by both pathways. In light of the major role that these pathways play in numerous types of cancer, we anticipate that the emerging discoveries being made about the function of the primary cilium in signaling pathways that are critical for embryonic development and tissue homeostasis in adults will also provide novel insights into the molecular mechanisms of carcinogenesis. (Cancer Res 2006; 66(15): 6463-7)
Association of MutantTP53with Alternative Lengthening of Telomeres and Favorable Prognosis in Glioma
Authors: Chen Yu-Jen , Hakin-Smith Vicky , Teo Mario , Xinarianos George E. , Jellinek David A. , Carroll Thomas , McDowell David , MacFarlane Martin R. , Boet Ronald , Baguley Bruce C. , Braithwaite Antony W. , Reddel Roger R. , Royds Janice A.
Published: July 2006

The molecular basis for alternative lengthening of telomeres (ALT), a prognostic marker for glioma patients, remains unknown. We examined TP53 status in relation to telomere maintenance mechanism (TMM) in 108 patients with glioblastoma multiforme and two patients with anaplastic astrocytoma from New Zealand and United Kingdom. Tumor samples were analyzed with respect to telomerase activity, telomere length, and ALT-associated promyelocytic leukemia nuclear bodies to determine their TMM. TP53 mutation was analyzed by direct sequencing of coding exons 2 to 11. We found an association between TP53 mutation and ALT mechanism and between wild-type TP53 and telomerase and absence of a known TMM (P < 0.0001). We suggest that TP53 deficiency plays a permissive role in the activation of ALT. (Cancer Res 2006; 66(13): 6473-6)
'Mission In Christ's Way': The Way of Which Christ?
Authors: Robinson Gnana
Published: July 2006

All Churches and Missionary Movements in different parts of the world assert without hesitation that in all that they do, they follow the way of Jesus Christ. But the gross injustice in international economic dealings promoted by the so-called 'Christian Nations' in the world and the consequent widening of the gap between the rich and the poor in the world, the discrimination of people on the basis of creed, class, race and colour practised by many Christians and the power-struggle and corruption found in many local churches make the world wonder, the way of which Christ these Christians follow! The image of the Biblical Jesus is that of the Servant-leader, crowned with thorns, who emptied himself of all worldly riches, pomp and power and laid down his life as a ransom for many. Since the time of Emperor Constantine, this thorn-crowned servant Jesus is turned into a gold-crowned King, an anti-Christ with the face of 'Mammon', the idol of riches and power. Since one cannot worship God and Mammon at the same time, it is mandatory on the part of us all faithful Christians, to introspect ourselves and decide, the way of which Christ we want to follow.
Continuity and Discontinuity in Conversion Stories
Authors: Speelman Gé
Published: July 2006

In this article, I focus on continuity and discontinuity between religious traditions, as perceived by converts. I interviewed six converts: three Muslims who became Christian, three Christians who converted to Islam. They reflect on their experiences with their 'old' and 'new' religion. What were the changes they underwent? What remained the same? In their stories, they often conclude that God remained a constant presence in their life, even if they did not experience this at an earlier stage.
Sentencing Outcomes Under Competing But Coexisting Sentencing Interventions: Untying The Gordian Knot
Authors: Kautt Paula M. , Delone Miriam A.
Published: July 2006

The latest evolutionary phase of criminal sentencing is a return to determinate sentencing structures. However, the concurrent application of sentencing guidelines and mandatory minimum statutes in various jurisdictions often distorts and convolutes evaluations of such interventions’ effectiveness. To remedy this problem, the effects of such distinct reforms must be separated from one another. Previous research has been unsuccessful in accomplishing this task. The authors attempt to remedy this deficiency by using 1997-1998 federal sentencing data to isolate the effects of the minima from those of the guidelines and assessing how the predictors and conditioners of sentencing outcomes vary between them. The authors find several significant and some unexpected differences in the effect of predictors across models of incarceration and sentence length for the two intervention types.
Protesting Privilege
Authors: Magnet Shoshana
Published: July 2006

In this article, the author uses autoethnographic methods to interrogate her own White privilege. She argues that it is necessary to consider both how people are positioned as dominant as well as how they are positioned as marginalized to deconstruct persisting hierarchies of oppression. Drawing on a series of conversations that took place during the passage of several years, the author interrogates her willingness to hide behind her own minority identities and privilege, and she considers the importance of this undertaking to feminist politics and praxis.
The Islamic Worldview of Adult Learning in the Workplace: Surrendering to God
Authors: Akdere Mesut , Russ-Eft Darlene , Eft Natalie
Published: July 2006

The problem and the solution. As the second largest religion on earth, Islam has been in existence for more than 14 centuries. Today, Islam continues to grow in many parts of the world, including Europe and North America where Muslims comprise a notable minority. As our societies become more diverse, it is not uncommon in many major cities to have a Muslim colleague at work, classmate in school, or neighbor in the community. These areas are within the practice and research realm of human resource development (HRD). Therefore, understanding and appreciating the Islamic worldview of adult learning and the daily practices of its followers will contribute to resolving philosophical and cultural clashes in the work of HRD professionals as trainers, researchers, educators, and consultants throughout the world.
Maori and Pakeha Perspectives of Adult Learning in Aotearoa/New Zealand Workplaces
Authors: Papuni Helen T. , Bartlett Kenneth R.
Published: July 2006

The problem and the solution. Descendants of many cultures have made Aotearoa/New Zealand their home but there exists a unique historical treaty-based relationship between the two main settler groups of the Maori (descendants of the first Polynesian settlers of 800 AD) and the Pakeha (descendants of the first British settlers of 1800 AD). Although much human resources literature still reflects a colonial bias, New Zealand’s workforce relations now incorporate both Maori and Pakeha cultural customs. Using a dialectic approach, this article investigates the Maori influence in the changing culture of human resource development in Aotearoa/ New Zealand.
Using Computer-Assisted Qualitative Data Analysis Software to Develop a Grounded Theory Project
Authors: Bringer Joy D. , Johnston Lynne Halley , Brackenridge Celia H.
Published: July 2006

The promise of theory and model development makes grounded theory an attractive methodology to follow. However, it has been argued that many researchers fall short and provide a detailed description of only the research area or simply a quantitative content analysis rather than an explanatory model. This article illustrates how the researchers used a computer-assisted qualitative data analysis software program (CAQDAS) as a tool for moving beyond a thick description of swimming coaches' perceptions of sexual relationships in sport to an explanatory model grounded in the data. Grounded theory is an iterative process whereby the researchers move between data collection and analysis, writing memos, coding, and creating models. The nonlinear design of the selected CAQDAS program, NVIVO, facilitates such iterative approaches. Although the examples provided in this project focus on NVIVO, the concepts presented here could be applied to the use of other CAQDAS programs. Examples are provided of how the grounded theory techniques of open coding, writing memos, axial coding, and creating models were conducted within the program.
Cutaneous wound healing is impaired in hemophilia B
Authors: Hoffman Maureane , Harger Anna , Lenkowski Angela , Hedner Ulla , Roberts Harold R. , Monroe Dougald M.
Published: July 2006

We used a mouse model to test the hypothesis that the time course and histology of wound healing is altered in hemophilia B. Punch biopsies (3 mm) were placed in the skin of normal mice and mice with hemophilia. The size of the wounds was measured daily until the epidermal defect closed. All wounds closed in mice with hemophilia by 12 days, compared with 10 days in normal animals. Skin from the area of the wound was harvested at different time points and examined histologically. Hemophilic animals developed subcutaneous hematomas; normal animals did not. Macrophage infiltration was significantly delayed in hemophilia B. Unexpectedly, hemophilic mice developed twice as many blood vessels in the healing wounds as controls, and the increased vascularity persisted for at least 2 weeks. The deposition and persistence of ferric iron was also greater in hemophilic mice. We hypothesize that iron plays a role in promoting excess angiogenesis after wounding as it had been proposed to do in hemophilic arthropathy. We have demonstrated that impaired coagulation leads to delayed wound healing with abnormal histology. Our findings have significant implications for treatment of patients with hemophilia, and also highlight the importance of rapidly establishing hemostasis following trauma or surgery.
A pyridinium derivative from Red Sea soft corals inhibited voltage-activated potassium conductances and increased excitability of rat cultured sensory neurones
Authors: Temraz Tarek A , Houssen Wael E , Jaspars Marcel , Woolley David R , Wease Kerrie N , Davies Steven N , Scott Roderick H
Published: July 2006

Background

Whole cell patch clamp recording and intracellular Ca2+ imaging were carried out on rat cultured dorsal root ganglion (DRG) neurones to characterize the actions of crude extracts and purified samples from Red Sea soft corals. The aim of the project was to identify compounds that would alter the excitability of DRG neurones.

Results

Crude extracts of Sarcophyton glaucum and Lobophyton crassum attenuated spike frequency adaptation causing DRG neurones to switch from firing single action potentials to multiple firing. The increase in excitability was associated with enhanced KCl-evoked Ca2+ influx. The mechanism of action of the natural products in the samples from the soft corals involved inhibition of voltage-activated K+ currents. An active component of the crude marine samples was identified as 3-carboxy-1-methyl pyridinium (trigonelline). Application of synthetic 3-carboxy-1-methyl pyridinium at high concentration (0.1 mM) also induced multiple firing and reduced voltage-activated K+ current. The changes in excitability of DRG neurones induced by 3-carboxy-1-methyl pyridinium suggest that this compound contributes to the bioactivity produced by the crude extracts from two soft corals.

Conclusion

Sarcophyton glaucum and Lobophyton crassum contain natural products including 3-carboxy-1-methyl pyridinium that increase the excitability of DRG neurones. We speculate that in addition to developmental control and osmoregulation these compounds may contribute to chemical defenses.
WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity
Authors: Latthe Pallavi , Latthe Manish , Say Lale , Gülmezoglu Metin , Khan Khalid S
Published: July 2006

Background

Health care planning for chronic pelvic pain (CPP), an important cause of morbidity amongst women is hampered due to lack of clear collated summaries of its basic epidemiological data. We systematically reviewed worldwide literature on the prevalence of different types of CPP to assess the geographical distribution of data, and to explore sources of variation in its estimates.

Methods

We identified data available from Medline (1966 to 2004), Embase (1980 to 2004), PsycINFO (1887 to 2003), LILACS (1982 to 2004), Science Citation index, CINAHL (January 1980 to 2004) and hand searching of reference lists. Two reviewers extracted data independently, using a piloted form, on participants' characteristics, study quality and rates of CPP. We considered a study to be of high quality (valid) if had at least three of the following features: prospective design, validated measurement tool, adequate sampling method, sample size estimation and response rate >80%. We performed both univariate and multivariate meta-regression analysis to explore heterogeneity of results across studies.

Results

There were 178 studies (459975 participants) in 148 articles. Of these, 106 studies were (124259 participants) on dysmenorrhoea, 54 (35973 participants) on dyspareunia and 18 (301756 participants) on noncyclical pain. There were only 19/95 (20%) less developed and 1/45 (2.2%) least developed countries with relevant data in contrast to 22/43 (51.2%) developed countries. Meta-regression analysis showed that rates of pain varied according to study quality features. There were 40 (22.5%) high quality studies with representative samples. Amongst them, the rate of dysmenorrhoea was 16.8 to 81%, that of dyspareunia was 8 to 21.8%, and that for noncyclical pain was 2.1 to 24%.

Conclusion

There were few valid population based estimates of disease burden due to CPP from less developed countries. The variation in rates of CPP worldwide was due to variable study quality. Where valid data were available, a high disease burden of all types of pelvic pain was found.
Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease
Authors: Wang Xipeng , Deavers Michael , Patenia Rebecca , Bassett Roland L , Mueller Peter , Ma Qing , Wang Ena , Freedman Ralph S
Published: July 2006

Background

We previously showed that tumor-free peritoneum of patients with epithelial ovarian cancer (EOC) exhibited enhanced expression of several inflammatory response genes compared to peritoneum of benign disease. Here, we examined peritoneal inflammatory cell patterns to determine their concordance with selected enhanced genes.

Methods

Expression patterns of selected inflammatory genes were mined from our previously published data base. Bilateral pelvic peritoneal and subjacent stromal specimens were obtained from 20 women with EOC and 7 women with benign pelvic conditions. Sections were first stained by indirect immunoperoxidase and numbers of monocytes/macrophages (MO/MA), T cells, B cells, and NK cells counted. Proportions of CD68+ cells and CD3+ cells that coexpressed MO/MA differentiation factors (CD163, CCR1, CXCR8, VCAM1, and phosphorylated cytosolic phospholipase A2[pcPLA2]), which had demonstrated expression in EOC peritoneal samples, were determined by multicolor immunofluorescence.

Results

MO/MA were present on both sides of the pelvic peritoneum in EOC patients, with infiltration of the subjacent stroma and mesothelium. CD68+ MO/MA, the most commonly represented population, and CD3+ T cells were present more often in EOC than in benign pelvic tumors. NK cells, B cells, and granulocytes were rare. CXCL8 (IL-8) and the chemokine receptor CCR1 were coexpressed more frequently on MO/MA than on CD3+ cells contrasting with CD68+/CD163+ cells that coexpressed CXCL8 less often. An important activated enzyme in the eicosanoid pathway, pcPLA2, was highly expressed on both CD68+ and CD163+ cells. The adherence molecule Vascular Cell Adhesion Molecule-1 (VCAM1) was expressed on CD31+ endothelial cells and on a proportion of CD68+ MO/MA but rarely on CD3+ cells.

Conclusion

The pelvic peritoneum in EOC exhibits a general pattern of chronic inflammation, represented primarily by differentiated MO/MA, and distinct from that in benign conditions concordant with previous profiling results.
Reemergence of dengue virus type-3 (subtype-III) in India: Implications for increased incidence of DHF & DSS
Authors: Dash Paban Kumar , Parida Man Mohan , Saxena Parag , Abhyankar Ajay , Singh CP , Tewari KN , Jana Asha Mukul , Sekhar K , Rao PV Lakshmana
Published: July 2006

Background

Dengue virus infection has recently taken endemic proportion in India implicating all the four known dengue serotypes. There was a major dengue outbreak in northern India including Delhi in October- December, 2003 and again in 2004. We have carried out a detailed investigation of the 2004 outbreak by Serosurveillance, RT-PCR, nested PCR, virus isolation and genotyping. We also report the molecular epidemiological investigation of these outbreaks.

Results

The serological investigation of 162 suspected serum samples using an in-house dengue dipstick ELISA revealed 11%-IgM, 51%-IgG and 38%-both IgM and IgG antibody positivity. The RT-PCR analysis revealed presence of dengue RNA in 17 samples. Further subtyping and genotyping by nested PCR and nucleotide sequencing of C-prM gene junction revealed the association of subtype III of dengue virus type 3 in the outbreak.

Conclusion

The sudden shifting and dominance of the dengue virus serotype-3 (subtype III) replacing the earlier circulating serotype-2 (subtype IV) is a point of major concern and may be attributed to increased incidence of DHF and DSS in India.
Epidermal Growth Factor Receptor as a Therapeutic Target in Human Thyroid Carcinoma: Mutational and Functional Analysis
Authors: Mitsiades Constantine S. , Kotoula Vassiliki , Poulaki Vassiliki , Sozopoulos Elias , Negri Joseph , Charalambous Elpida , Fanourakis Galinos , Voutsinas Gerassimos , Tseleni-Balafouta Sophia , Mitsiades Nicholas
Published: July 2006

Context: The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase (TK) receptor that mediates proliferation and survival signaling, is expressed in a wide variety of normal and neoplastic tissues. EGFR inhibitors have produced objective responses in patients with non-small-cell lung carcinomas harboring activating EGFR TK domain somatic mutations.

Objective and Methods: Because the EGFR pathway has been reported to be important for the pathophysiology of thyroid carcinoma, we investigated the expression and mutational status of EGFR in 14 thyroid carcinoma cell lines as well as its functional role by evaluating their in vitro sensitivity to AEE788, a new dual-family EGFR/ErbB2 and vascular endothelial growth factor receptor TK inhibitor. We also evaluated the mutational status, mRNA and protein expression, as well as phosphorylation status of EGFR in a panel of thyroid carcinoma specimens.

Results: EGFR expression and phosphorylation in the thyroid carcinoma cell lines and tissue specimens were present but not stronger than in noncancerous thyroid tissue. EGFR TK domain mutations were detected in two of 62 histological specimens (3.2%) but not in cell lines. All thyroid carcinoma cell lines were significantly less sensitive (IC50 at least 25-fold higher) in vitro to AEE788 than a primary culture of EGFR-mutant lung carcinoma cells.

Conclusions: Thyroid carcinoma cells overall are poorly responsive to clinically relevant concentrations of AEE788 in vitro. The presence of EGFR-activating TK domain mutations may identify a small minority of thyroid cancer patients that may benefit from EGFR inhibitors, but additional preclinical evidence of efficacy is needed.
Genotyping of Five Chinese Patients with 17α-Hydroxylase Deficiency Diagnosed through High-Performance Liquid Chromatography Serum Adrenal Profile: Identification of Two Novel CYP17 Mutations
Authors: Wei Ji-Qing , Wei Ji-Lu , Li Wei-Chun , Bi Yun-Sheng , Wei Feng-Cai
Published: July 2006

Context: 17α-Hydroxylase deficiency is a rare form of congenital adrenal hyperplasia caused by CYP17 gene mutations.

Objective: Five Chinese patients with 17α-hydroxylase deficiency were genotyped.

Patients: The five patients derived from four families living in Shandong Province, China. The diagnosis of 17α-hydroxylase deficiency was initially established through HPLC serum adrenal profiles in Qilu Hospital, China, from 1983–1993.

Results: Three CYP17 gene mutations were identified from these patients. Among them, V311fs and Y329fs are two novel frame-shifting mutations. V311fs is an 8-bp nucleotide (TTAAATGG) deletion in exon 5. Y329fs is a deletion-insertion combined mutation (TAC→AA) at codon 329 in exon 6. Two homozygotes for Y329fs and one compound heterozygote for Y329fs and V311fs were identified from three different families. Two homozygous sisters for the D487_S488_F489 deletion were identified.

Conclusion: The results confirmed the diagnostic value of the HPLC serum adrenal profile for 17α-hydroxylase deficiency. The D487_S488_F489 deletion had been identified in two previously genotyped Chinese families. In our present study, a third Chinese family with this mutation was identified, suggesting that this mutation is a prevalent CYP17 mutation in the Chinese population. The identification of Y329fs mutation in addition to three previously identified mutations at codon 329 suggests that codon 329 is an unstable point of the CYP17 gene. The mutations identified from our five patients appear to be random, but the recurrence of the Y329fs mutation may be attributed to a founder effect. Our studies suggest that 17α-hydroxylase deficiency may not be rare in the Chinese population.
Water-Induced Thermogenesis Reconsidered: The Effects of Osmolality and Water Temperature on Energy Expenditure after Drinking
Authors: Brown Clive M. , Dulloo Abdul G. , Montani Jean-Pierre
Published: July 2006

Context: A recent study reported that drinking 500 ml of water causes a 30% increase in metabolic rate. If verified, this previously unrecognized thermogenic property of water would have important implications for weight-loss programs. However, the concept of a thermogenic effect of water is controversial because other studies have found that water drinking does not increase energy expenditure.

Objective: The objective of the study was to test whether water drinking has a thermogenic effect in humans and, furthermore, determine whether the response is influenced by osmolality or by water temperature.

Design: This was a randomized, crossover design.

Setting: The study was conducted at a university physiology laboratory.

Participants: Participants included healthy young volunteer subjects.

Intervention: Intervention included drinking 7.5 ml/kg body weight (∼518 ml) of distilled water or 0.9% saline or 7% sucrose solution (positive control) on different days. In a subgroup of subjects, responses to cold water (3 C) were tested.

Main Outcome Measure: Resting energy expenditure, assessed by indirect calorimetry for 30 min before and 90 min after the drinks, was measured.

Results: Energy expenditure did not increase after drinking either distilled water (P = 0.34) or 0.9% saline (P = 0.33). Drinking the 7% sucrose solution significantly increased energy expenditure (P < 0.0001). Drinking water that had been cooled to 3 C caused a small increase in energy expenditure of 4.5% over 60 min (P < 0.01).

Conclusions: Drinking distilled water at room temperature did not increase energy expenditure. Cooling the water before drinking only stimulated a small thermogenic response, well below the theoretical energy cost of warming the water to body temperature. These results cast doubt on water as a thermogenic agent for the management of obesity.
Optically Active N,N′-Bis(3-oxobutylidene)diaminatomanganese(III) Complexes as Novel and Efficient Catalysts for Aerobic Enantioselective Epoxidation of Simple Olefins
Authors: Nagata Takushi , Imagawa Kiyomi , Yamada Tohru , Mukaiyama Teruaki
Published: July 2006

A novel manganese(III) complex having an optically active N,N′-bis(3-oxobutylidene)diamine ligand with bulky substituents was prepared and characterized crystallographically. In the presence of a catalytic amount of the manganese(III) complex, unfunctionalized olefins were oxygenated to give optically active epoxides with molecular oxygen by the combined use of several aliphatic aldehydes. Cyclic and acyclic cis-β-substituted styrene derivatives, conjugated dienes, and enynes were converted into the corresponding epoxides with moderate-to-good enantioselectivities. The present aerobic and enantioselective epoxidation proceeded with the opposite enantioface selection from those obtained by using terminal oxidants, such as sodium hypochlorite and iodosylbenzene. The key intermediate of the aerobic asymmetric epoxidation is also discussed.
Generation and Reactions of Trifluoroacetimidoyl Radicals
Authors: Dan-oh Yasufumi , Matta Hirokazu , Uemura Junko , Watanabe Hisayuki , Uneyama Kenji
Published: July 2006

N-Aryltrifluoroacetimidoyl radicals have been generated by three different methods: the tin-radical promoted deiodination and photochemical homolysis of imidoyl iodides and the thermal homolysis of imidoyl azo-compounds. N-[2-(1-alkynyl)phenyl]trifluoroacetimidoyl iodides have been converted to trifluoromethylated indoles by the tin-radical promoted homolysis of the carbon–iodine bond followed by intramolecular cyclization. The photolysis of trifluoroacetimidoyl iodides enabled both intra- and intermolecular cyclization to indoles and quinolines. Likewise, thermal reactions of N-(2,2,2-trifluoro-1-tritylazoethylidene)anilines provided trifluoromethylated quinolines and indoles.
Representation of Future and Previous Spatial Goals by Separate Neural Populations in Prefrontal Cortex
Authors: Genovesio Aldo , Brasted Peter J. , Wise Steven P.
Published: July 2006

The primate prefrontal cortex plays a central role in choosing goals, along with a wide variety of additional functions, including short-term memory. In the present study, we examined neuronal activity in the prefrontal cortex as monkeys used abstract response strategies to select one of three spatial goals, a selection that depended on their memory of the most recent previous goal. During each trial, the monkeys selected a future goal on the basis of events from the previous trial, including both the symbolic visual cue that had appeared on that trial and the previous goal that the monkeys had selected. When a symbolic visual cue repeated from the previous trial, the monkeys stayed with their previous goal as the next (future) goal; when the cue changed, the monkeys shifted from their previous goal to one of the two remaining locations as their future goal. We found that prefrontal neurons had activity that reflected either previous goals or future goals, but only rarely did individual cells reflect both. This finding suggests that essentially separate neural networks encode these two aspects of spatial information processing. A failure to distinguish previous and future goals could lead to two kinds of maladaptive behavior. First, wrongly representing an accomplished goal as still pending could cause perseveration or compulsive checking, two disorders commonly attributed to dysfunction of the prefrontal cortex. Second, mistaking a pending goal as already accomplished could cause the failures of omission that occur commonly in dementia.
Dopamine D3Receptor Agonist Delivery to a Model of Parkinson's Disease Restores the Nigrostriatal Pathway and Improves Locomotor Behavior
Authors: Van Kampen Jackalina M. , Eckman Christopher B.
Published: July 2006

The presence of endogenous stem cell populations in the adult mammalian CNS suggests an innate potential for regeneration and represents a potential resource for neuroregenerative therapy aimed at the treatment of neurodegenerative disorders, such as Parkinson's disease. However, it is first necessary to examine the microenvironmental signals required to activate these innate reparative mechanisms. The small molecule neurotransmitter dopamine has been shown to regulate cell cycle in developing and adult brain, and the D3receptor is known to play an important role in dopaminergic development. Pharmacological activation of the dopamine D3receptor has been shown to trigger neurogenesis in the substantia nigra of the adult rat brain. Here, we examined the cell proliferative, neurogenic, and behavioral effects of the dopamine D3receptor agonist 7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin) in a 6-hydroxydopamine model of Parkinson's disease. Consistent with previous findings, we observed a significant induction of cell proliferation in the substantia nigra pars compacta (SNC) with a time-dependent adoption of a neuronal dopaminergic phenotype in many of these cells. Indices of nigrostriatal integrity were also affected. Dopaminergic cell counts in the lesioned SNCrecovered substantially in a time-dependent manner. Similarly, retrograde tracing revealed a restoration of striatal innervation from these cells, with evidence for projections arising from newly generated cells. Finally, we observed a substantial and persistent recovery of locomotor function in these animals. The results of these studies will further our understanding of the environmental signals regulating neurogenesis in the adult brain and could have significant implications for the design of novel treatment strategies for Parkinson's disease.
The Neural Basis of Interindividual Variability in Inhibitory Efficiency after Sleep Deprivation
Authors: Chuah Y. M. Lisa , Venkatraman Vinod , Dinges David F. , Chee Michael W. L.
Published: July 2006

Sleep deprivation results in the loss of our ability to suppress a prepotent response. The extent of decline in this executive function varies across individuals. Here, we used functional magnetic resonance imaging to study the neural correlates of sleep deprivation-induced differences in inhibitory efficiency. Participants performed a go/no-go task after normal sleep and after 24 h of total sleep deprivation. Regardless of the extent of change in inhibitory efficiency, sleep deprivation lowered go/no-go sustained, task-related activation of the ventral and anterior prefrontal (PFC) regions bilaterally. However, individuals better able to maintain inhibitory efficiency after sleep deprivation could be distinguished by lower stop-related, phasic activation of the right ventral PFC during rested wakefulness. These persons also showed a larger rise in such activation both here and in the right insula after sleep deprivation relative to those whose inhibitory efficiency declined.
Zinc Modulates Bidirectional Hippocampal Plasticity by Effects on NMDA Receptors
Authors: Izumi Yukitoshi , Auberson Yves P. , Zorumski Charles F.
Published: July 2006

Zinc has complex effects on NMDA receptors (NMDARs) and may be an endogenous modulator of synaptic plasticity. In the CA1 region of rat hippocampal slices, we observed that low micromolar concentrations of zinc depress NMDAR synaptic responses by 40–50% and inhibit long-term depression (LTD) but not long-term potentiation (LTP). A combination of zinc plus ifenprodil, an inhibitor of NR1/NR2B receptors, produced no greater inhibition of synaptic NMDARs than either agent alone, suggesting overlapping effects on NMDARs. Similar to low micromolar zinc, ifenprodil inhibited LTD but not LTP. In contrast, low concentrations of 2-amino-5-phosphonovalerate (APV) did not block either LTP or LTD despite producing >50% inhibition of synaptic NMDARs. NVP-AAM077 ([(R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4-tetrahydro-quinoxalin-5-yl)-methyl]phosphonic acid), an antagonist with relative NR1/NR2A selectivity at low concentrations, also inhibited synaptic NMDARs by ∼50% at 0.05 μmbut failed to completely block either LTP or LTD. These results suggest that LTD induction depends on specific NMDARs with sensitivity to low micromolar zinc and ifenprodil, but LTP is less dependent on specific NMDAR subtypes. Because high-affinity sites of NR2A are likely occupied by ambient zinc, we also examined effects of extracellular zinc chelators. Zinc chelation blocked LTP but had no effect on LTD. This LTP inhibition was overcome by APV and NVP-AAM077 but not ifenprodil, suggesting that zinc chelation unmasks tonic NR1/NR2A activation that negatively modulates LTP.
Local Protein Synthesis and Spine Morphogenesis: Fragile X Syndrome and Beyond
Authors: Grossman Aaron W. , Aldridge Georgina M. , Weiler Ivan Jeanne , Greenough William T.
Published: July 2006

Behavioral experiences can modulate neural networks through changes in synaptic morphology and number. In contrast, abnormal morphogenesis of dendritic spines is associated with cognitive impairment, as in Fragile X syndrome. Dendritic or synaptic protein synthesis could provide the specificity and speed necessary for spine morphogenesis. Here, we highlight locally translated proteins shown to affect synaptic morphology (e.g., Fragile X mental retardation protein).