bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced store-operated Ca2+entry in pulmonary endothelial cells from chronically hypoxic rats
Authors: Paffett Michael L. , Naik Jay S. , Resta Thomas C. , Walker Benjimen R.
Published: August 2007

Chronic hypoxia (CH)-induced pulmonary hypertension may influence basal endothelial cell (EC) intracellular Ca2+concentration ([Ca2+]i). We hypothesized that CH decreases EC [Ca2+]iassociated with membrane depolarization and reduced Ca2+entry. To test this hypothesis, we assessed 1) basal endothelial Ca2+in pressurized pulmonary arteries and freshly isolated ECs, 2) EC membrane potential ( Em), 3) store-operated Ca2+current ( ISOC), and 4) store-operated Ca2+(SOC) entry in arteries from control and CH rats. We found that basal EC Ca2+was significantly lower in pressurized pulmonary arteries and freshly isolated ECs from CH rats compared with controls. Similarly, ECs in intact arteries from CH rats were depolarized compared with controls, although no differences were observed between groups in isolated cells. ISOCactivation by 1 μM thapsigargin displayed diminished inward current and a reversal potential closer to 0 mV in cells from CH rats compared with controls. In addition, SOC entry determined by fura 2 fluorescence and Mn2+quenching revealed a parallel reduction in Ca2+entry following CH. We conclude that differences in the magnitude of SOC entry exist between freshly dispersed ECs from CH and control rats and correlates with the decrease in basal EC [Ca2+]i. In contrast, basal EC Ca2+influx is unaffected and membrane depolarization is limited to intact arteries, suggesting that Emmay not play a major role in determining basal EC [Ca2+]ifollowing CH.
Angiogenesis is induced by airway smooth muscle strain
Authors: Hasaneen Nadia A. , Zucker Stanley , Lin Richard Z. , Vaday Gayle G. , Panettieri Reynold A. , Foda Hussein D.
Published: August 2007

Angiogenesis is an important feature of airway remodeling in both chronic asthma and chronic obstructive pulmonary disease (COPD). Airways in those conditions are exposed to excessive mechanical strain during periods of acute exacerbations. We recently reported that mechanical strain of human airway smooth muscle (HASM) led to an increase in their proliferation and migration. Sustained growth in airway smooth muscle in vivo requires an increase in the nutritional supply to these muscles, hence angiogenesis. In this study, we examined the hypothesis that cyclic mechanical strain of HASM produces factors promoting angiogenic events in the surrounding vascular endothelial cells. Our results show: 1) a significant increase in human lung microvascular endothelial cell (HMVEC-L) proliferation, migration, and tube formation following incubation in conditioned media (CM) from HASM cells exposed to mechanical strain; 2) mechanical strain of HASM cells induced VEGF expression and release; 3) VEGF neutralizing antibodies inhibited the proliferation, migration, and tube formations of HMVEC-L induced by the strained airway smooth muscle CM; 4) mechanical strain of HASM induced a significant increase in hypoxia-inducible factor-1α (HIF-1α) mRNA and protein, a transcription factor required for VEGF gene transcription; and 5) mechanical strain of HASM induced HIF-1α/VEGF through dual phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and ERK pathways. In conclusion, exposing HASM cells to mechanical strain induces signal transduction pathway through PI3K/Akt/mTOR and ERK pathways that lead to an increase in HIF-1α, a transcription factor required for VEGF expression. VEGF release by mechanical strain of HASM may contribute to the angiogenesis seen with repeated exacerbation of asthma and COPD.
Phase-Locked Responses to Pure Tones in the Auditory Thalamus
Authors: Wallace Mark N. , Anderson Lucy A. , Palmer Alan R.
Published: August 2007

Accurate temporal coding of low-frequency tones by spikes that are locked to a particular phase of the sine wave (phase-locking), occurs among certain groups of neurons at various processing levels in the brain. Phase-locked responses have previously been studied in the inferior colliculus and neocortex of the guinea pig and we now describe the responses in the auditory thalamus. Recordings were made from 241 single units, 32 (13%) of which showed phase-locked responses. Units with phase-locked responses were mainly (82%) located in the ventral division of the medial geniculate body (MGB), and also the medial division (18%), but were not found in the dorsal or shell divisions. The upper limiting frequency of phase-locking varied greatly between units (60–1,100 Hz) and between anatomical divisions. The upper limit in the ventral division was 520 Hz and in the medial was 1,100 Hz. The range of steady-state delays calculated from phase plots also varied: ventral division, 8.6–14 ms (mean 11.1 ms; SD 1.56); medial division, 7.5–11 ms (mean 9.3 ms; SD 1.5). Taken together, these measurements are consistent with the medial division receiving a phase-locked input directly from the brain stem, without an obligatory relay in the inferior colliculus. Cells in both the ventral and medial divisions of the MGB showed a response that phase-locked to the fundamental frequency of a guinea pig purr and may be involved in analyzing communication calls.
Sequential Down-regulation of E-Cadherin with Squamous Cell Carcinoma Progression: Loss of E-Cadherin via a Prostaglandin E2-EP2–Dependent Posttranslational Mechanism
Authors: Brouxhon Sabine , Kyrkanides Stephanos , O'Banion M. Kerry , Johnson Renee , Pearce David A. , Centola Gina M. , Miller Jen-nie H. , McGrath Kieran H. , Erdle Brandon , Scott Glynis , Schneider Sandra , VanBuskirk JoAnne , Pentland Alice P.
Published: August 2007

The incidence of skin cancer is on the rise, with over 1 million new cases yearly. Although it is known that squamous cell cancers (SCC) are caused by UV light, the mechanism(s) involved remains poorly understood. In vitro studies with epithelial cells or reports examining malignant skin lesions suggest that loss of E-cadherin–mediated cell-cell contacts may contribute to SCCs. Other studies show a pivotal role for cyclooxygenase-dependent prostaglandin E2 (PGE2) synthesis in this process. Using chronically UV-irradiated SKH-1 mice, we show a sequential loss of E-cadherin–mediated cell-cell contacts as lesions progress from dysplasia to SCCs. This E-cadherin down-regulation was also evident after acute UV exposure in vivo. In both chronic and acute UV injury, E-cadherin levels declined at a time when epidermal PGE2 synthesis was enhanced. Inhibition of PGE2 synthesis by indomethacin in vitro, targeted deletion of EP2 in primary mouse keratinocyte (PMK) cultures or deletion of the EP2 receptor in vivo abrogated this UV-induced E-cadherin down-regulation. In contrast, addition of PGE2 or the EP2 receptor agonist butaprost to PMK produced a dose- and time-dependent decrease in E-cadherin. We also show that UV irradiation, via the PGE2-EP2 signaling pathway, may initiate tumorigenesis in keratinocytes by down-regulating E-cadherin–mediated cell-cell contacts through its mobilization away from the cell membrane, internalization into the cytoplasm, and shuttling through the lysosome and proteasome degradation pathways. Further understanding of how UV-PGE2-EP2 down-regulates E-cadherin may lead to novel chemopreventative strategies for the treatment of skin and other epithelial cancers. [Cancer Res 2007;67(16):7654–64]
Up-regulation of 14-3-3ζ in Lung Cancer and Its Implication as Prognostic and Therapeutic Target
Authors: Fan Tao , Li Ruiyun , Todd Nevins W. , Qiu Qi , Fang Hong-Bin , Wang Huijun , Shen Jianjun , Zhao Richard Y. , Caraway Nancy P. , Katz Ruth L. , Stass Sanford A. , Jiang Feng
Published: August 2007

A functional genomic approach integrating microarray and proteomic analyses done in our laboratory has identified 14-3-3ζ as a putative oncogene whose activation was common and driven by its genomic amplification in lung adenocarcinomas. 14-3-3ζ is believed to function in cell signaling, cycle control, and apoptotic death. Following our initial finding, here, we analyzed its expression in lung tumor tissues obtained from 205 patients with various histologic and stage non–small cell lung cancers (NSCLC) using immunohistochemistry and then explored the effects of specific suppression of the gene in vitro and in a xenograft model using small interfering RNA. The increased 14-3-3ζ expression was positively correlated with a more advanced pathologic stage and grade of NSCLCs (P = 0.001 and P = 0.006, respectively) and was associated with overall and cancer-specific survival rates of the patients (P = 0.022 and P = 0.018, respectively). Down-regulation of 14-3-3ζ in lung cancer cells led to a dose-dependent increased sensitivity to cisplatin-induced cell death, which was associated with the inhibition of cell proliferation and increased G2-M arrest and apoptosis. The result was further confirmed in the animal model, which showed that the A549 lung cancer cells with reduced 14-3-3ζ grew significantly slower than the wild-type A549 cells after cisplatin treatment (P = 0.008). Our results suggest that 14-3-3ζ is a potential target for developing a prognostic biomarker and therapeutics that can enhance the antitumor activity of cisplatin for NSCLC. [Cancer Res 2007;67(16):7901–6]
The let-7 MicroRNA Represses Cell Proliferation Pathways in Human Cells
Authors: Johnson Charles D. , Esquela-Kerscher Aurora , Stefani Giovanni , Byrom Mike , Kelnar Kevin , Ovcharenko Dmitriy , Wilson Mike , Wang Xiaowei , Shelton Jeffrey , Shingara Jaclyn , Chin Lena , Brown David , Slack Frank J.
Published: August 2007

MicroRNAs play important roles in animal development, cell differentiation, and metabolism and have been implicated in human cancer. The let-7 microRNA controls the timing of cell cycle exit and terminal differentiation in Caenorhabditis elegans and is poorly expressed or deleted in human lung tumors. Here, we show that let-7 is highly expressed in normal lung tissue, and that inhibiting let-7 function leads to increased cell division in A549 lung cancer cells. Overexpression of let-7 in cancer cell lines alters cell cycle progression and reduces cell division, providing evidence that let-7 functions as a tumor suppressor in lung cells. let-7 was previously shown to regulate the expression of the RAS lung cancer oncogenes, and our work now shows that multiple genes involved in cell cycle and cell division functions are also directly or indirectly repressed by let-7. This work reveals the let-7 microRNA to be a master regulator of cell proliferation pathways. [Cancer Res 2007;67(16):7713–22]
The Development and Characterization of a Human Midgut Carcinoid Cell Line
Authors: Van Buren George , Rashid Asif , Yang Anthony D. , Abdalla Eddie K. , Gray Michael J. , Liu Wenbiao , Somcio Ray , Fan Fan , Camp E. Ramsay , Yao James C. , Ellis Lee M.
Published: August 2007

Purpose: Gastrointestinal neuroendocrine tumors (NET) are rare heterogeneous tumors that hypersecrete neuropeptides. The scarcity of good gastrointestinal NET models has limited the ability to study potential therapeutic agents. We describe and characterize the establishment of a human midgut carcinoid tumor cell line carcinoid tumor 2 (CNDT2).

Experimental Design: Tumor cells (CNDT2) were isolated from a liver metastasis from a patient with a primary ileal carcinoid. After 9 weeks in culture, the cells were plated in soft agar, and cells from a single colony were put back in culture (CNDT2.1). Those CNDT2.1 cells were injected s.c. into nude mice. Cells were isolated from a single resultant tumor (CNDT2.5), cultured, and characterized by electron microscopy, reverse transcription-PCR, serotonin enzyme immunoassay, Western blotting, and immunohistochemical analysis for NET markers and potential therapeutic targets.

Results: CNDT2 cells grew in monolayers in vitro, formed colonies in soft agar, and formed tumors in mice. Electron microscopy revealed round, pleomorphic, electron-dense neurosecretory granules characteristic of NETs. Tumor xenografts exhibited the appearance of NETs with small “salt-and-pepper” nuclei on H&E staining and chromogranin A, synaptophysin, and CD56 on immunohistochemical staining. CNDT2.5 cells produced serotonin and expressed insulin-like growth factor receptor-I, platelet-derived growth factor receptor-β, vascular endothelial growth factor receptor-1, cMET, epidermal growth factor receptor, neuropilin-1, and somatostatin receptors 1 to 5. Cytogenetic analysis revealed the presence of deletions at 2p and 6q and numerous translocations.

Conclusion: The establishment of this human midgut carcinoid tumor cell line may serve as a useful model system for studying cell biology and novel targeted agents in preclinical models.
Hydroxamic Acid Analogue Histone Deacetylase Inhibitors Attenuate Estrogen Receptor-α Levels and Transcriptional Activity: A Result of Hyperacetylation and Inhibition of Chaperone Function of Heat Shock Protein 90
Authors: Fiskus Warren , Ren Yuan , Mohapatra Alex , Bali Purva , Mandawat Aditya , Rao Rekha , Herger Bryan , Yang Yonghua , Atadja Peter , Wu Jie , Bhalla Kapil
Published: August 2007

Purpose: The molecular chaperone heat shock protein (hsp)-90 maintains estrogen receptor (ER)-α in an active conformation, allowing it to bind 17β-estradiol (E2) and transactivate genes, including progesterone receptor (PR)-β and the class IIB histone deacetylase HDAC6. By inhibiting HDAC6, the hydroxamic acid analogue pan-HDAC inhibitors (HA-HDI; e.g., LAQ824, LBH589, and vorinostat) induce hyperacetylation of the HDAC6 substrates α-tubulin and hsp90. Hyperacetylation of hsp90 inhibits its chaperone function, thereby depleting hsp90 client proteins. Here, we determined the effect of HA-HDIs on the levels and activity of ERα, as well as on the survival of ERα-expressing, estrogen-responsive human breast cancer MCF-7 and BT-474 cells.

Experimental Design: Following exposure to HA-HDIs, hsp90 binding, polyubiquitylation levels, and transcriptional activity of ERα, as well as apoptosis and loss of survival, were determined in MCF-7 and BT-474 cells.

Results: Treatment with HA-HDI induced hsp90 hyperacetylation, decreased its binding to ERα, and increased polyubiquitylation and depletion of ERα levels. HA-HDI treatment abrogated E2-induced estrogen response element-luciferase expression and attenuated PRβ and HDAC6 levels. Exposure to HA-HDI also depleted p-Akt, Akt, c-Raf, and phospho-extracellular signal–regulated kinase-1/2 levels, inhibited growth, and sensitized ERα-positive breast cancer cells to tamoxifen.

Conclusions: These findings show that treatment with HA-HDI abrogates ERα levels and activity and could sensitize ERα-positive breast cancers to E2 depletion or ERα antagonists.
Secreted Frizzled-Related Protein 1 Loss Contributes to Tumor Phenotype of Clear Cell Renal Cell Carcinoma
Authors: Gumz Michelle L. , Zou Hongzhi , Kreinest Pamela A. , Childs April C. , Belmonte Leandra S. , LeGrand Shauna N. , Wu Kevin J. , Luxon Bruce A. , Sinha Mala , Parker Alexander S. , Sun L-Z. , Ahlquist David A. , Wood Christopher G. , Copland John A.
Published: August 2007

Purpose: Incidence and mortality rates for renal cell carcinoma (RCC) have been rising for decades. Unfortunately, the molecular events that support RCC carcinogenesis remain poorly understood. In an effort to gain a better understanding of signaling events in clear cell RCC (cRCC), we investigated the antitumor activity of secreted frizzled-related protein 1 (sFRP1), a negative regulator of Wnt signaling.

Experimental Design: Genomic profiling of cRCC tumors and patient-matched normal tissues was done and confirmed using quantitative PCR and immunohistochemistry. Methylation-specific PCR was done on patient samples to evaluate the mechanism responsible for sFRP1 loss. sFRP1 expression was restored in cRCC cells and the effects on tumor phenotype were characterized.

Results: Genomic profiling, quantitative PCR, and immunohistochemistry indicated that loss of sFRP1 occurred in cRCC and papillary RCC patient tissues. Twelve Wnt-regulated genes were up-regulated in cRCC tissues, including c-myc and cyclin D1, potentiators of cell proliferation and survival. Methylation of the sFRP1 gene was one mechanism identified for attenuation of sFRP1 mRNA. Stable reexpression of sFRP1 in cRCC cells resulted in decreased expression of Wnt target genes, decreased growth in cell culture, inhibition of anchorage-independent growth, and decreased tumor growth in athymic nude mice.

Conclusions: To our knowledge, this is the first report to show that stable restoration of sFRP1 expression in cRCC cells attenuates the cRCC tumor phenotype. Our data support a role for sFRP1 as a tumor suppressor in cRCC and that perhaps loss of sFRP1 is an early, aberrant molecular event in renal cell carcinogenesis.
Vascular Endothelial Growth Factor-Trap Overcomes Defects in Dendritic Cell Differentiation but Does Not Improve Antigen-Specific Immune Responses
Authors: Fricke Ingo , Mirza Noweeda , Dupont Jakob , Lockhart Craig , Jackson Autumn , Lee Ji-Hyun , Sosman Jeffrey A. , Gabrilovich Dmitry I.
Published: August 2007

Purpose: Induction of antitumor immune responses requires adequate function of dendritic cells. Dendritic cell defects in cancer patients have been implicated in tumor escape and the limited efficacy of cancer vaccines. Previous studies have shown that vascular endothelial growth factor (VEGF) plays a major role in abnormal dendritic cell differentiation and function in cancer. It has been proposed that inhibition of VEGF may result in improved immune responses. The goal of this study was to test this hypothesis.

Experimental Design: Fifteen patients with refractory solid tumors were enrolled into a phase I clinical trial of VEGF-Trap. Phenotype and function of different subsets of mononuclear cells were measured before and at different time points after the start of treatment.

Results: VEGF-Trap treatment did not affect the total population of dendritic cells, their myeloid or plasmacytoid subsets, myeloid-derived suppressor cells (MDSC), or regulatory T cells. It significantly increased the proportion of mature dendritic cells. However, that improvement was not associated with an overall increase in immune responses to various antigens and mitogens. A subset analysis revealed significant improvement in immune responses in patients who had no increase in the proportion of MDSC. An improvement in immune responses was absent in patients with an increase in the proportion of MDSC.

Conclusions: Inhibition of VEGF signaling may improve differentiation of dendritic cells in cancer patients. However, it was not sufficient to improve immune responses. This shows multifaceted nature of immune deficiency and points out to the need for complex approach to modulation of immune reactivity in cancer.
Sorafenib Inhibits the Imatinib-Resistant KIT
T670I Gatekeeper Mutation in Gastrointestinal Stromal Tumor
Authors: Guo Tianhua , Agaram Narasimhan P. , Wong Grace C. , Hom Glory , D'Adamo David , Maki Robert G. , Schwartz Gary K. , Veach Darren , Clarkson Bayard D. , Singer Samuel , DeMatteo Ronald P. , Besmer Peter , Antonescu Cristina R.
Published: August 2007

Purpose: Resistance is commonly acquired in patients with metastatic gastrointestinal stromal tumor who are treated with imatinib mesylate, often due to the development of secondary mutations in the KIT kinase domain. We sought to investigate the efficacy of second-line tyrosine kinase inhibitors, such as sorafenib, dasatinib, and nilotinib, against the commonly observed imatinib-resistant KIT mutations (KITV654A, KITT670I, KITD820Y, and KITN822K) expressed in the Ba/F3 cellular system.

Experimental Design: In vitro drug screening of stable Ba/F3 KIT mutants recapitulating the genotype of imatinib-resistant patients harboring primary and secondary KIT mutations was investigated. Comparison was made to imatinib-sensitive Ba/F3 KIT mutant cells as well as Ba/F3 cells expressing only secondary KIT mutations. The efficacy of drug treatment was evaluated by proliferation and apoptosis assays, in addition to biochemical inhibition of KIT activation.

Results: Sorafenib was potent against all imatinib-resistant Ba/F3 KIT double mutants tested, including the gatekeeper secondary mutation KITWK557-8del/T670I, which was resistant to other kinase inhibitors. Although all three drugs tested decreased cell proliferation and inhibited KIT activation against exon 13 (KITV560del/V654A) and exon 17 (KITV559D/D820Y) double mutants, nilotinib did so at lower concentrations.

Conclusions: Our results emphasize the need for tailored salvage therapy in imatinib-refractory gastrointestinal stromal tumors according to individual molecular mechanisms of resistance. The Ba/F3 KITWK557-8del/T670I cells were sensitive only to sorafenib inhibition, whereas nilotinib was more potent on imatinib-resistant KITV560del/V654A and KITV559D/D820Y mutant cells than dasatinib and sorafenib.
AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models
Authors: Davies Barry R. , Logie Armelle , McKay Jennifer S. , Martin Paul , Steele Samantha , Jenkins Richard , Cockerill Mark , Cartlidge Sue , Smith Paul D.
Published: August 2007

Constitutive activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signaling pathway in human cancers is often associated with mutational activation of BRAF or RAS. MAPK/ERK kinase 1/2 kinases lie downstream of RAS and BRAF and are the only acknowledged activators of ERK1/2, making them attractive targets for therapeutic intervention. AZD6244 (ARRY-142886) is a potent, selective, and ATP-uncompetitive inhibitor of MAPK/ERK kinase 1/2. In vitro cell viability inhibition screening of a tumor cell line panel found that lines harboring BRAF or RAS mutations were more likely to be sensitive to AZD6244. The in vivo mechanisms by which AZD6244 inhibits tumor growth were investigated. Chronic dosing with 25 mg/kg AZD6244 bd resulted in suppression of growth of Colo-205, Calu-6, and SW-620 xenografts, whereas an acute dose resulted in significant inhibition of ERK1/2 phosphorylation. Increased cleaved caspase-3, a marker of apoptosis, was detected in Colo-205 and Calu-6 but not in SW-620 tumors where a significant decrease in cell proliferation was detected. Chronic dosing of AZD6244 induced a morphologic change in SW-620 tumors to a more differentiated phenotype. The potential of AZD6244 in combination with cytotoxic drugs was evaluated in mice bearing SW-620 xenografts. Treatment with tolerated doses of AZD6244 and either irinotecan or docetaxel resulted in significantly enhanced antitumor efficacy relative to that of either agent alone. These results indicate that AZD6244 has potential to inhibit proliferation and induce apoptosis and differentiation, but the response varies between different xenografts. Moreover, enhanced antitumor efficacy can be obtained by combining AZD6244 with the cytotoxic drugs irinotecan or docetaxel. [Mol Cancer Ther 2007;6(8):2209–19]
Rapamycin inhibits multiple stages of c-Neu/ErbB2–induced tumor progression in a transgenic mouse model of HER2-positive breast cancer
Authors: Mosley Jonathan D. , Poirier John T. , Seachrist Darcie D. , Landis Melissa D. , Keri Ruth A.
Published: August 2007

Amplification of the HER2 (ErbB2, c-Neu) proto-oncogene in breast cancer is associated with poor prognosis and high relapse rates. HER2/ErbB2, in conjunction with ErbB3, signals through the Akt/phosphatidylinositol 3-kinase pathway and leads to the activation of mammalian target of rapamycin (mTOR), a critical mRNA translation regulator that controls cell growth. Gene expression analysis of mammary tumors collected from mouse mammary tumor virus-c-Neu transgenic mice revealed that mRNA levels of several mTOR pathway members were either up-regulated (p85/phosphatidylinositol 3-kinase and p70S6 kinase) or down-regulated (eIF-4E-BP1) in a manner expected to enhance signaling through this pathway. Treatment of these mice with the mTOR inhibitor rapamycin caused growth arrest and regression of primary tumors with no evidence of weight loss or generalized toxicity. The treatment effects were due to decreased proliferation, associated with reduced cyclin D1 expression, and increased cell death in primary tumors. Whereas many of the dead epithelial cells had the histopathologic characteristics of ischemic necrosis, rapamycin treatment was not associated with changes in microvascular density or apoptosis. Rapamycin also inhibited cellular proliferation in lung metastases. In summary, data from this preclinical model of ErbB2/Neu-induced breast cancer show that inhibition of the mTOR pathway with rapamycin blocks multiple stages of ErbB2/Neu-induced tumorigenic progression. [Mol Cancer Ther 2007;6(8):2188–97]
Immune Response Induced by a Different Combined Immunization of HBsAg Vaccine
Authors: Wu Ting , Chen Min , Ou Shan-Hai , Cheng Tong , Zhang Jun , Xia Ning-Shao
Published: August 2007

Aims: To evaluate the immune responses induced by different combined immunizations of HBsAg protein vaccine (P), recombinant vaccinia virus vaccine (V) and DNA vaccine (D). Methods: Balb/c mice were primed by one of the three HBsAg vaccines P, V or D and boosted by the same or another, thus nine immune combinations were constructed. Titers of anti-HBsAg IgG and their sub-isotypes were determined by ELISA. Specific cellular immune responses were determined by calcein-release assay. Results: V could induce the quickest humoral immune response with the geometrical mean titer of 1:101.6 at week 2 after prime immunization. The antibody titer primed by P (including PP, PV, PD) mounted up to the highest after the first boost. Antibody induced by PP was more polarized to Th2 while the other groups induced balanced Th1/Th2 response. Among all the groups, VD and DV induced the strongest CTL response. After the fourth boost, the specific lysis ratio was 64 and 71% separately at an E:T ratio of 1:1. Conclusions: P was the most potent for inducing humoral immune response while the weakest for CTL response. D was a poor immunogen to induce specific antibody production. Among all the immune combinations, DV and VD induced the strongest CTL response in Balb/c mice.
Continuous Venovenous Hemofiltration with or without Predilution Regional Citrate Anticoagulation: A Prospective Study
Authors: Nurmohamed S. Azam , Vervloet Marc G. , Girbes Armand R.J. , Ter Wee Pieter M. , Groeneveld A.B. Johan
Published: August 2007

Background/Aims: Continuous venovenous hemofiltration (CVVH) requires anticoagulation to prevent circuit clotting and its use is contraindicated in patients with high bleeding risk. The aim of this study was to compare CVVH with and without regional citrate anticoagulation (RCA) with respect to filter life, azotemic control and cost. Methods: This was a prospective sequential cohort study. The first cohort of patients with a high bleeding risk and acute renal failure was treated by anticoagulant-free predilution CVVH (n = 31). In the second cohort, CVVH was applied with RCA (n = 20). Results: The median filter life was 41 h (interquartile range 20–62) with RCA and 12 h (8–28) without RCA (p = 0.001). The azotemic control was better in the group with RCA. The hourly cost was comparable between the two groups. Conclusion: Regional anticoagulation with citrate-based replacement solution improved filter life compared to anticoagulant-free predilution CVVH. This regimen appeared safe, feasible and without metabolic complications or increased costs.
Thallium-201 SPECT predicts response to intensity-modulated radiation therapy for recurrent oral squamous cell carcinoma
Authors: Lee J. K. , Liu W. S. , Lin Y. S. , Liu J. T. , Chang L. P. , Chou M. C. , Huang W. S.
Published: August 2007

The aim of this study was designed to investigate the usefulness of thallium-201 single photon emission computed tomography (SPECT) in predicting response of intensitymodulated radiation therapy (IMRT) for recurrent oral squamous cell carcinoma (OSCC). Patients, methods: Thirty-one patients with histologically proven recurrent OSCC were recruited. Before IMRT, all patients underwent SPECT at 15 min and 120 min after intravenous injection 111 MBq of thallous chloride (201Tl). Tumour uptake was measured with the semiquantitative early ratio (ER), delayed ratio (DR), and retention index (RI). The patients were classified into responder (complete response and partial response) and non-responder (stable disease and progressive disease) groups according to the tumour response evaluated by the Response Evaluation Criteria in Solid Tumors guidelines. Results: As comparing DR and RI between the two groups, both parameters were significantly higher in the responder group. When a DR of 1.75 was used as a cutoff value for the responders, the receiver operating characteristic (ROC) analyses revealed sensitivity and specificity of 79% and 75%, respectively. At a cutoff value for the responders of a RI of 78.5%, the ROC analyses showed sensitivity and specificity of 95% and 83%, respectively. Conclusion: Our results suggest that 201Tl-SPECT, as measured by the DR or RI has clinical potential in predicting response of IMRT for patients with recurrent OSCC. The ROC curve analyses further suggest that RI may be superior to DR in distinguishing responders from non-responders.
Guideline for radioiodine therapy for benign thyroid diseases (version 4)
Authors: Dressler J. , Grünwald F. , Leisner B. , Moser E. , Reiners Chr. , Schicha H. , Schneider P. , Schober O. , Dietlein M. ,   für die Deutsche Gesellschaft für Nuklearmedizin (DGN)
Published: August 2007

Version 4 of the guideline for radioiodine therapy for benign thyroid diseases includes an interdisciplinary consensus on decision making for antithyroid drugs, surgical treatment and radioiodine therapy. The quantitative description of a specific goiter volume for radioiodine therapy or operation was cancelled. For patients with nodular goiter with or without autonomy, manifold circumstances are in favor of surgery (suspicion on malignancy, large cystic nodules, mediastinal goiter, severe compression of the trachea) or in favor of radioiodine therapy (treatment of autonomy, age of patient, co-morbidity, history of prior subtotal thyroidectomy, profession like teacher, speaker or singer). For patients with Graves' disease, radioiodine therapy or surgery are recommended in the constellation of high risk of relapse (first-line therapy), persistence of hyperthyroidism or relapse of hyperthyroidism. After counseling, the patient gives informed consent to the preferred therapy. The period after radioiodine therapy of benign disorders until conception of at least four months was adapted to the European recommendation.
The Other Rabī': Biographical Traditions and the Development of Early Shāfi'ī Authority
Authors: Jaques R. Kevin
Published: August 2007

This article examines the biographical traditions that developed around al-Rabī b. Sulaymān al-Jīzī (d. 256/872) who, by the Mamlūk period, was widely viewed as a disciple of Muhammad b. Idrīs al-Shāfi'ī (d. 204/820). Against this view, I demonstrate that scholars working in the 4th/10th century depicted al-Jīzī as a follower of the Mālikī movement in Egypt. These scholars also suggested that some traditions transmitted by al-Rabī' b. Sulaymān al-Murādī (d. 270/884) were mistakenly attributed to al-Jīzī. By the 5th/11th century, new legal ideas had surfaced that conflicted with those said to have been transmitted by al-Murādī from al-Shāfi'ī. In order to save al-Murādī's reputation as the faithful and trustworthy transmitter of al-Shāfi'ī's final legal views, al-Jīzī was reinvented as a companion of al-Shāfi'ī so that legal ideas that conflicted with those found in the Kitāb al-umm could be attributed to him instead of al-Murādī.
Judicial Practice in Islamic Criminal Law In Nigeria—a Tentative Overview
Authors: Weimann Gunnar
Published: August 2007

Uniquely, in Nigeria Islamic Criminal Law was introduced in the framework of a secular federal constitution. In 2000 and 2001, twelve Northern states adopted legislation on the hadd offences and the Islamic law on homicide and bodily harm. Reliable statistics on the number of cases tried under the new laws are unavailable. Based on information from the media and human rights organisations, I present roughly 125 criminal cases tried before Nigerian Sharī'a courts between 2000 and 2004. This sample shows that Sharī'a was particularly enforced in states dominated by the Hausa. In religiously mixed states, the bid to introduce Sharī'a became part of the religious groups' competition for hegemony and access to public resources, with violent consequences. The expectations which many Muslims attached to the introduction of Sharī'a were inflated. Its impact on the security of life and property, the fight against corruption and the promotion of good governance has probably been minimal.
Judicial Activism and Islamic Family Law: A Socio-Legal Evaluation of Recent Trends in Bangladesh
Authors: Hoque Ridwanul , Khan MD. Morshed Mahmud
Published: August 2007

This article critically examines instances of judicial activism in the field of Islamic family law in Bangladesh in an attempt to assess this judicial trend. Seeing 'judicial activism' mainly as an enlightened application of ijtihād and also as society-specific application of statutes based on, or related to sharī'ah, we highlight the justice-ameliorative role of this concept. The authors argue that judicial activism has led to the amelioration of the status of women in Bangladesh as compared to a traditional construction of the sharī'ah, and that judges have adequate authority and legitimacy to develop Islamic family law to ensure better justice in the home. We conclude that modernist judicial reform is not only desirable but also inevitable in the current South Asian socio-legal milieu, where legislative passivity vis-à-vis Islamic family law prevails.
"Learning to Speak Horse": The Culture of "Natural Horsemanship"
Authors: Birke Lynda
Published: August 2007

This paper examines the rise of what is popularly called "natural horsemanship" (NH), as a definitive cultural change within the horse industry. Practitioners are often evangelical about their methods, portraying NH as a radical departure from traditional methods. In doing so, they create a clear demarcation from the practices and beliefs of the conventional horse-world. Only NH, advocates argue, properly understands the horse. Dissenters, however, contest the benefits to horses as well as the reliance in NH on disputed concepts of the natural. Advocates, furthermore, sought to rename technologies associated with riding while simultaneously condemning technologies used in conventional training (such as whips). These contested differences create boundaries and enact social inclusion and exclusion, which the paper explores. For horses, the impact of NH is ambiguous: Depending on practitioners, effects could be good or bad. However, for the people involved, NH presents a radical change—which they see as offering markedly better ways of relating to horses and a more inclusive social milieu.
Imaging Extinction: Disclosure and Revision in Photographs of the Thylacine (Tasmanian tiger)
Authors: Freeman Carol
Published: August 2007

The thylacine was a shy and elusive nonhuman animal who survived in small numbers on the island of Tasmania, Australia, when European settlers arrived in 1803. After a deliberate campaign of eradication, the species disappeared 130 years later. Visual and verbal constructions in the nineteenth century labeled the thylacine a ferocious predator, but photographs of individuals in British and American zoos that were used to illustrate early twentieth-century zoological works presented a very different impression of the animal. The publication of these photographs, however, had little effect on the relentless progress of extermination. This essay focuses on the relationship between photographs of thylacines and the process of extinction, between images and words, and between pictures of dead animals and live ones. The procedures, claims, and limitations of photography are crucial to the messages generated by these images and to the role they played in the representation of the species. This essay explains why the medium of photography and pleas for preservation could not save the thylacine.
How Ravens Came to the Tower of London
Authors: Sax Boria
Published: August 2007

According to popular belief, Charles II of England (reigned 1660-1685) once heard a prophecy that if ravens left the Tower of London it would "fall," so he ordered that the wings of seven ravens in the Tower be trimmed. Until recently, this claim was not challenged even in scholarly literature. There are, however, no allusions to the Tower Ravens before the end of the nineteenth century. The ravens, today meticulously cared for by Yeoman Warders, are largely an invented tradition, designed to give an impression of continuity with the past. This article examines the few known references, both graphic and textual, to the Tower Ravens through 1906. It concludes that the ravens were originally brought in to dramatize the alleged site of executions at the Tower. Although not accorded great significance at first, legends that would eventually make the ravens mascots of Britain began outside of the Tower.
Nematodes of the order Rhabditida from Tehran province, Iran. The genus Acrobeles von Linstow, 1877 with description of A. iranicus sp. n.
Authors: Shokoohi Ebrahim , Abolafia Joaquín , Zad Javad
Published: August 2007

A new species of the genus Acrobeles is described from natural areas in Tehran province, Iran. Acrobeles iranicus sp. n. is characterised by having a body 400–441 μ m long in females, 'double' cuticle with rows of interannular punctations, lateral field with two incisures, labial probolae 9–12 μ m long, pharyngeal corpus slightly fusiform and 2–4 times isthmus length, postuterine sac 5–15 μ m or 0.2–0.5 times as long as body diam. and bearing larger cells in its proximal part and conical female tail (31–36 μ m, c = 11.5–13.6, c′ = 2.3–2.9). In addition, Iranian populations of another three previously known species are studied: A. andalusicus, A. complexus and A. singulus, the third species having the male described for the first time. Descriptions, measurements and illustrations, including SEM photographs, are provided for all four species.
Tenuidraconema tongaense n. sp. (Nematoda: Draconematidae), a new free-living marine nematode from a seamount in the southwest Pacific Ocean
Authors: Rho Hyun Soo , Min Won Gi , Kim Dong Sung
Published: August 2007

A new species of free-living marine draconematid nematode, Tenuidraconema
tongaense n. sp., is described. This new species was collected from shallow
subtidal dead corals and detritus from a seamount in a hydrothermal area off
the Tonga Islands, southwest Pacific Ocean. Tenuidraconema tongaense n. sp.
differs from the known species of the genus by the following combination of
characters: longer body (1060-1265 μ m), position of 12 cephalic adhesion
tubes (anterior six cephalic adhesion tubes inserted on rostrum and
posterior six adhesion tubes inserted on anterior body annule in male; all
12 cephalic adhesion tubes inserted on rostrum in female), number of
posterior sublateral adhesion tubes (11 in male, 12 in female) and posterior
subventral adhesion tubes (9-11 in male, 10-11 in female) with somatic setae
intermingled between the two anteriormost sublateral adhesion tubes, longer
spicule length (43-50 μ m), and slender body (a = 41.1-48.6 in male and
29.4-35.1 in female). A pictorial key and a dichotomous identification key
for males and females are provided for the species. A table comparing the
major differential diagnostic characteristics of the species of
Tenuidraconema is presented.
The effect of five composts of different origin on the survival and reproduction of Globodera rostochiensis
Authors: Renčo Marek , D'Addabbo Trifone , Sasanelli Nicola , Papajová Ingrid
Published: August 2007

Five composts of different origin (C1: fresh olive pomace, straw, chicken manure and urea; C2: fresh olive pomace, cow manure, lettuce residues, straw and sawdust; C3: sewage sludge and municipal green residues; C4: grass, leaves, tree branches and soil; C5: by-product from penicillin production (mycelium), straw and sawdust, were tested for the control of the cyst nematode, Globodera rostochiensis, on potato in pot experiments. Composts were mixed with the nematode-infested soil at the rates of 1.0, 2.5, 5.0 and 10.0% w/w. A significant reduction in the number of eggs and juveniles was observed at all concentrations of the tested composts; compost from olive pomace mixed with urea resulted in the greatest decrease.
The embryonic cell lineage of the nematode Halicephalobus gingivalis (Nematoda: Cephalobina: Panagrolaimoidea)
Authors: Houthoofd Wouter , Borgonie Gaëtan
Published: August 2007

This paper describes the nearly complete embryonic cell lineage of the terrestrial nematode, Halicephalobus gingivalis, up to somatic muscle contraction, resulting in the formation of 536 cells, of which 24 undergo programmed cell death. Halicephalobus gingivalis has a 94% lineage homology with both Caenorhabditis elegans and Pellioditis marina, and a fate homology of only 86% and 78%, respectively. Although H. gingivalis belongs to a different superfamily than C. elegans and P. marina, its cell lineage is remarkably consistent with them. Variations in the fate distribution of cells among the different species were only observed at the end of the cell lineage. The data presented here show that the polyclonal cell specification is much more widespread in clades 9 and 10 and is not a highly derived trait that is specifically linked to the fast development of the model organism C. elegans.
Reliability of PCR-based techniques for detection and discrimination of plant-parasitic nematodes of sugarcane
Authors: Berry Shaun , Fargette Mireille , Morand Serge , Cadet Patrice
Published: August 2007

In order to develop diagnostic tools for plant-parasitic nematodes of
sugarcane in South Africa, this work investigated the potential biodiversity
of these nematodes in the amount of nucleic acid available, the
discrimination of species by a PCR-based method (targeting the ITS1 region)
and the effect of some experimental conditions on their detection or
discrimination. The ITS1 amplified fragment varied in size, ranging from 400
bp (Meloidogyne javanica) to 1200 bp (Longidorus pisi, Paratrichodorus
minor, Xiphinema elongatum, Xiphinema zulu). Some species discrimination was
possible by discernible differences in ITS1 amplified fragment sizes. The
potential, as well as shortcomings (inhibitions, competition) of this
approach are assessed and further steps/outcomes discussed. Part of the work
also focused on DNA extraction. Nematode genomic nucleic acid was extracted
from five nematode species (Pratylenchus zeae, Helicotylenchus dihystera,
Meloidogyne javanica, Xiphinema elongatum and Paratrichodorus lobatus) and
we discuss the significant differences obtained between species in the
amount of nucleic acid extracted. There were also marked differences in the
quantity and quality of nucleic acid extracted from nematode suspensions
originating from soils, depending on the extraction buffer used.
How do nematodes get their sweets? Solute supply to sedentary plant-parasitic nematodes
Authors: Hofmann Julia , Grundler Florian
Published: August 2007

Sedentary cyst and root-knot nematodes withdraw large amounts of solutes from feeding structures induced in host roots. The feeding structures are specialised cells with a high metabolic activity and a tremendous capacity in translocation of nutrients. The required nutrients are provided by the plant transport systems – water and inorganic solutes from the xylem, assimilates such as sugars and amino acids from the phloem. Here we discuss the available data on the mechanisms by which nutrients are translocated into the nematode feeding sites. The interaction between Heterodera schachtii and Arabidopsis thaliana serves as a model system for cyst nematodes. In this case sufficient data are available to propose a conclusive concept for the mechanisms of nutrient flow: basically, in the early stages of nematode development syncytia are symplasmically isolated, so that transport proteins are responsible for the nutrient supply. Later, connections to the phloem via plasmodesmata are established, so that developing females are well supplied with assimilates. The interactions of root-knot nematodes with their hosts share a number of similarities but the data currently available are not sufficient to draw similar conclusions. As nutrient supply and functionality of feeding structures are the basis of biotrophic parasitism of sedentary nematodes, it is tempting to unravel the mechanisms by which both plant and nematodes influence each other via nutrient fluxes.
The Quest for a Glocal Public Theology
Authors: Pearson Clive
Published: August 2007

Will Storrar makes the case for a glocal public theology arguing that where the practitioner is located matters. The underlying assumption is the need for 'good partners' and the possibility of theologies in one site critically informing another. What needs to be negotiated is the extent to which these 'partnerships' are uneven. The idea of a public theology surfaced in the established centres of the western theological tradition, but how can the categories of a public theology developed in the United States, for example, inform the shape of a comparable theology in Australia? The benefit of exploring this question is that it enables the history and critical scholarship of two locations to be named. For the more solid establishment of a public theology in Australia this is a strategic task, since the term is being used increasingly, but with arguably insufficient attention being paid to meaning, definition and task.
Embracing a Threatening Other: Identity and Reconciliation in Northern Ireland
Authors: Clegg Cecelia
Published: August 2007

In exploring the interaction between reconciliation and identity in the process of making peace in post-conflict Northern Ireland, this article argues that while political and inter-personal levels of reconciliation are important, it is societal reconciliation which is pivotal in securing the sustainability of 'peace'. The article offers a detailed definition of 'social reconciliation' which it locates in the development of a multi-layered typology of reconciliation. The implications of what it claims is the necessary re-negotiation of identities in a post-conflict society are teased out with reference to the situation in Northern Ireland. Some contours of the need to embrace the other, even a threatening other, are sketched.
Tilling and Caring for the Earth: Public Theology and Ecology
Authors: Bedford-Strohm Heinrich
Published: August 2007

This article examines the task of public theology in contributing to the public debate by drawing from theological resources for ethical orientation and at the same time explaining why this orientation makes good sense for all people of good will. From a concrete example, the different factors involved in political decisions on ecologically relevant issues are revealed. Three fundamental types of defining the relationship between human beings and non-human nature can be identified: a utilitarian anthropocentrism that radically subordinates non-human nature to the interests of humanity; a nature-centred approach that sees humanity embedded in nature, equal with any other part of creation and, finally, an anthropocentrism of responsibility that affirms the dignity of nature while acknowledging a conflict between humanity and nonhuman nature. The article further develops the third approach as most appropriate for public theology and highlights the minimization of human violence as its consequence for political decisions.