bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormone-Induced Protection against Mammary Tumorigenesis Is Conserved in Multiple Rat Strains and Identifies a Core Gene Expression Signature Induced by Pregnancy
Authors: Blakely Collin M. , Stoddard Alexander J. , Belka George K. , Dugan Katherine D. , Notarfrancesco Kathleen L. , Moody Susan E. , D'Cruz Celina M. , Chodosh Lewis A.
Published: June 2006

Women who have their first child early in life have a substantially lower lifetime risk of breast cancer. The mechanism for this is unknown. Similar to humans, rats exhibit parity-induced protection against mammary tumorigenesis. To explore the basis for this phenomenon, we identified persistent pregnancy-induced changes in mammary gene expression that are tightly associated with protection against tumorigenesis in multiple inbred rat strains. Four inbred rat strains that exhibit marked differences in their intrinsic susceptibilities to carcinogen-induced mammary tumorigenesis were each shown to display significant protection against methylnitrosourea-induced mammary tumorigenesis following treatment with pregnancy levels of estradiol and progesterone. Microarray expression profiling of parous and nulliparous mammary tissue from these four strains yielded a common 70-gene signature. Examination of the genes constituting this signature implicated alterations in transforming growth factor-β signaling, the extracellular matrix, amphiregulin expression, and the growth hormone/insulin-like growth factor I axis in pregnancy-induced alterations in breast cancer risk. Notably, related molecular changes have been associated with decreased mammographic density, which itself is strongly associated with decreased breast cancer risk. Our findings show that hormone-induced protection against mammary tumorigenesis is widely conserved among divergent rat strains and define a gene expression signature that is tightly correlated with reduced mammary tumor susceptibility as a consequence of a normal developmental event. Given the conservation of this signature, these pathways may contribute to pregnancy-induced protection against breast cancer. (Cancer Res 2006; 66(12): 6421-31)
YC-1 Induces S Cell Cycle Arrest and Apoptosis by Activating Checkpoint Kinases
Authors: Yeo Eun-Jin , Ryu Ji-Hye , Chun Yang-Sook , Cho Young-Suk , Jang In-Jin , Cho HoSung , Kim Jinho , Kim Myung-Suk , Park Jong-Wan
Published: June 2006

Hypoxia-inducible factor-1α (HIF-1α) seems central to tumor growth and progression because it up-regulates genes essential for angiogenesis and the hypoxic adaptation of cancer cells, which is why HIF-1α inhibition is viewed as a cancer therapy strategy. Paradoxically, HIF-1α also leads to cell cycle arrest or the apoptosis of cancer cells. Thus, the possibility cannot be ruled out that HIF-1α inhibitors unlock cell cycle arrest under hypoxic conditions and prevent cell death, which would limit the anticancer effect of HIF-1α inhibitors. Previously, we reported on the development of YC-1 as an anticancer agent that inhibits HIF-1α. In the present study, we evaluated the effects of YC-1 on hypoxia-induced cell cycle arrest and cell death. It was found that YC-1 does not reverse the antiproliferative effect of hypoxia, but rather that it induces S-phase arrest and apoptosis at therapeutic concentrations that inhibit HIF-1α and tumor growth; however, YC-1 did not stimulate cyclic guanosine 3′,5′-monophosphate production in this concentration range. It was also found that YC-1 activates the checkpoint kinase–mediated intra-S-phase checkpoint, independently of ataxia-telangiectasia mutated kinase or ataxia-telangiectasia mutated and Rad3-related kinase. These results imply that YC-1 does not promote the regrowth of hypoxic tumors because of its cell cycle arrest effect. Furthermore, YC-1 may induce the combined anticancer effects of HIF-1α inhibition and cell growth inhibition. (Cancer Res 2006; 66(12): 6345-52)
Mutant p53 Induces the GEF-H1 Oncogene, a Guanine Nucleotide Exchange Factor-H1 for RhoA, Resulting in Accelerated Cell Proliferation in Tumor Cells
Authors: Mizuarai Shinji , Yamanaka Kazunori , Kotani Hidehito
Published: June 2006

The tumor suppressor gene p53 is known to induce G1-S and G2-M cell cycle arrest and apoptosis by transactivating various wild-type (WT) p53 regulatory genes. Mutational inactivation of p53 is detected in more than half of human cancers, depriving the p53 protein of its tumor-suppressive functions. Recent studies have shown that mutant p53 provides tumor cells with gain-of-function properties, such as accelerated cell proliferation, increased metastasis, and apoptosis resistance. However, the mechanism underlying the elevated tumorigenicity by p53 mutation remains to be elucidated. In the present study, we showed that GEF-H1, a guanine exchange factor-H1 for RhoA, is transcriptionally activated by the induction of mutant p53 proteins, thereby accelerating tumor cell proliferation. Osteosarcoma U2OS cell lines, which express inducible p53 mutants (V157F, R175H, and R248Q), were established, and the expression profiles of each cell line were then analyzed to detect genes specifically induced by mutant p53. We identified GEF-H1 as one of the consensus genes whose expression was significantly induced by the three mutants. The GEF-H1 expression level strongly correlated with p53 status in a panel of 32 cancer cell lines, and GEF-H1 induction caused activation of RhoA. Furthermore, growth of mutant p53 cells was dependent on GEF-H1 expression, whereas that of WT p53 cells was not. These results suggest that increased GEF-H1 expression contributes to the tumor progression phenotype associated with the p53 mutation. (Cancer Res 2006; 66(12): 6319-26)
The Epithelial Cell Transforming Sequence 2, a Guanine Nucleotide Exchange Factor for Rho GTPases, Is Repressed by p53 via Protein Methyltransferases and Is Required for G1-S Transition
Authors: Scoumanne Ariane , Chen Xinbin
Published: June 2006

The epithelial cell transforming sequence 2 (ECT2), a member of the Dbl family of guanine nucleotide exchange factor for Rho GTPases, is required for cytokinesis. The tumor suppressor p53 plays a crucial role in coordinating cellular processes, such as cell cycle arrest and apoptosis, in response to stress signals. Here, we showed that ECT2 is negatively regulated by wild-type p53 but not tumor-derived mutant p53 or other p53 family members. In addition, ECT2 is down-regulated in multiple cell lines by DNA damage agents and Nutlin-3, an MDM2 antagonist, in a p53-dependent manner. We also showed that the activity of the ECT2 promoter is repressed by wild-type p53, and to a lesser extent, by p21. In addition, the second activation domain in p53 is necessary for the efficient repression of ECT2. Importantly, we found that the ECT2 gene is bound by p53 in vivo in response to DNA damage and Nutlin-3 treatment. Furthermore, we provided evidence that inhibition of protein methyltransferases, especially arginine methyltransferases, relieve the repression of ECT2 induced by DNA damage or Nutlin-3 in a p53-dependent manner. Finally, we generated multiple cell lines in which ECT2 is inducibly knocked down and found that ECT2 knockdown triggers cell cycle arrest in G1. Taken together, we uncovered a novel function for ECT2 and provided a novel mechanism by which p53 represses gene expression via protein methyltransferases. (Cancer Res 2006; 66(12): 6271-9)
Tumor Growth Suppression in Pancreatic Cancer by a Putative Metastasis Suppressor Gene Cap43/NDRG1/Drg-1 through Modulation of Angiogenesis
Authors: Maruyama Yuichiro , Ono Mayumi , Kawahara Akihiko , Yokoyama Toshiro , Basaki Yuji , Kage Masayoshi , Aoyagi Shigeaki , Kinoshita Hisafumi , Kuwano Michihiko
Published: June 2006

Cap43 has been identified as a nickel- and calcium-induced gene, and is also known as N-myc downstream-regulated gene 1 (NDRG1), Drg-1 and rit42. It is also reported that overexpression of Cap43 suppresses metastasis of some malignancies, but its precise role remains unclear. In this study, we asked how Cap43 could modulate the tumor growth of pancreatic cancer. Stable Cap43 cDNA transfectants of pancreatic cancer cells with Cap43 overexpression showed similar growth rates in culture as their control counterparts with low Cap43 protein level. By contrast, Cap43 overexpression showed a marked decrease in tumor growth rates in vivo. Moreover, a marked reduction in tumor-induced angiogenesis was observed. Gelatinolytic activity by matrix metalloproteinase-9 and invasive ability in Matrigel invasion activity were markedly decreased in pancreatic cancer cell lines with high Cap43 expression. Cellular expression of matrix metalloproteinase-9 and two major angiogenic factors, vascular endothelial growth factor and interleukin-8, were also significantly decreased in cell lines with Cap43 overexpression as compared with their parental counterparts. Immunohistochemical analysis of specimens from 65 patients with pancreatic ductal adenocarcinoma showed a significant association between Cap43 expression and tumor microvascular density (P = 0.0001) as well as depth of invasion (P = 0.0003), histopathologic grading (P = 0.0244), and overall survival rates for patients with pancreatic cancer (P = 0.0062). Thus, Cap43 could play a key role in the angiogenic on- or off-switch of tumor stroma in pancreatic ductal adenocarcinoma. (Cancer Res 2006; 66(12): 6233-42)
NFKB1 Is a Direct Target of the TAL1 Oncoprotein in Human T Leukemia Cells
Authors: Chang Pei-Yun , Draheim Kyle , Kelliher Michelle A. , Miyamoto Shigeki
Published: June 2006

We recently showed that a subset of human T acute lymphoblastic leukemia (T-ALL) cell lines expresses low basal levels of p50, a nuclear factor-κB (NF-κB)/Rel family member, resulting in their capacity to activate the atypical p65:cRel complex rather than the classic p50:p65 dimer. Here, we show that the transcription factor TAL1 (also known as SCL) binds to the promoter of the NFKB1 gene that encodes p50 and represses its transcription to set up this unique response in T-ALL cells. When TAL1 expression is reduced in CEM T leukemia cells, basal NFKB1 expression is increased, and the levels of p65:cRel complex and transcription of its target gene, such as intercellular adhesion molecule-1 (ICAM-1), are reduced in response to etoposide treatment. Moreover, a significant negative correlation between NFKB1 and TAL1 or LMO1 was found in primary human TAL1/LMO1 double-positive T-ALL samples previously described by Ferrando et al. Thus, TAL1 modulates NFKB1 expression and an NF-κB-dependent transcriptional program in a subset of human T-cell leukemia cells. (Cancer Res 2006; 66(12): 6008-13)
Changes in Antitumor Response in C57BL/6J-Min/+ Mice during Long-term Administration of a Selective Cyclooxygenase-2 Inhibitor
Authors: Carothers Adelaide M. , Moran Amy E. , Cho Nancy L. , Redston Mark , Bertagnolli Monica M.
Published: June 2006

Selective cyclooxygenase-2 (COX-2) inhibitors are widely prescribed for severe arthritis and are currently under study in human chemoprevention trials. Recently, long-term use of these agents has come under scrutiny due to reports of treatment-associated cardiovascular toxicity. On short-term administration, the selective COX-2 inhibitor celecoxib inhibits adenoma growth in animal tumor models, including the C57BL/6J-Min/+ (Min/+) mouse. With uninterrupted long-term celecoxib administration, intestinal tumors in Min/+ mice initially regressed and then recurred to levels comparable with untreated controls. Celecoxib treatment initially suppressed COX-2 and prostaglandin E2 (PGE2) expression, but long-term use produced significantly higher levels of these molecules and reactivated PGE2-associated growth factor signaling pathways in tumor and normal tissues. These results indicate that COX-2 is an important chemoprevention target and that inhibition of this enzyme alters a paracrine enterocyte regulatory pathway. Chronic uninterrupted celecoxib treatment, however, induces untoward effects that enhance early progression events in intestinal tumorigenesis and may contribute to treatment toxicity. (Cancer Res 2006; 66(12): 6432-8)
Carcinoembryonic Antigen–Targeted Selective Gene Therapy for Gastric Cancer through FZ33 Fiber-Modified Adenovirus Vectors
Authors: Tanaka Toshihiro , Huang Jianhua , Hirai Sachie , Kuroki Motomu , Kuroki Masahide , Watanabe Naoki , Tomihara Kei , Kato Kazunori , Hamada Hirofumi
Published: June 2006

Purpose: A major problem when using the adenoviral vectors for gene therapy applications is thought to be related to low transduction efficiency in cancer cells or to side effects in normal cells. There is an urgent requirement to improve the specificity of gene delivery in the context of cancer gene therapy.

Experimental Design: We constructed a genetically modified adenovirus incorporating an IgG Fc-binding motif from the Staphylococcus protein A, Z33, within the HI loop (Adv-FZ33). A remarkable degree of targeted gene delivery to gastric cancer cells was obtained with Adv-FZ33 with the fully human anti–carcinoembryonic antigen (CEA) monoclonal antibody, C2-45.

Results: In vitro LacZ or EGFP gene expression after Adv-FZ33 infection via C2-45 was 20 times higher than control monoclonal antibody in MKN-45 at 1,000 viral particles/cell. We generated Ax3CAUP-FZ33 (UP-FZ33), which is an Adv-FZ33 derivative vector expressing a therapeutic gene (i.e., Escherichia coli uracil phosphoribosyltransferase), which converts 5-fluorouracil (5-FU) directly to 5-fluoro-UMP. UP-FZ33 with C2-45 enhanced the cytotoxicity of 5-FU by 10.5-fold in terms of IC50 against MKN-45 compared with control IgG4. In a nude mouse peritoneal dissemination model, tumor growth in mice treated with UP-FZ33/C2-45/5-FU was significantly suppressed, and tumor volumes were less than one-fourth of those of the control IgG4 group (P < 0.05). The median survival time of the UP-FZ33/C2-45/5-FU group was significantly longer than those treated with PBS or 5-FU only (P < 0.01).

Conclusions: These data suggest that CEA-targeted FZ33 mutant adenovirus-mediated gene delivery offers a strong and selective therapeutic modality against CEA-producing cancers.
Roles of KLF6 and KLF6-SV1 in Ovarian Cancer Progression and Intraperitoneal Dissemination
Authors: DiFeo Analisa , Narla Goutham , Hirshfeld Jennifer , Camacho-Vanegas Olga , Narla Jyothsna , Rose Stephen L. , Kalir Tamara , Yao Shen , Levine Alice , Birrer Michael J. , Bonome Tomas , Friedman Scott L. , Buller Richard E. , Martignetti John A.
Published: June 2006

Purpose: We investigated the role of the KLF6 tumor suppressor gene and its alternatively spliced isoform KLF6-SV1 in epithelial ovarian cancer (EOC).

Experimental Design: We first analyzed tumors from 68 females with EOC for KLF6 gene inactivation using fluorescent loss of heterozygosity (LOH) analysis and direct DNA sequencing and then defined changes in KLF6 and KLF6-SV1 expression levels by quantitative real-time PCR. We then directly tested the effect of KLF6 and KLF6-SV1 inhibition in SKOV-3 stable cell lines on cellular invasion and proliferation in culture and tumor growth, i.p. dissemination, ascites production, and angiogenesis in vivo using BALB/c nu/nu mice. All statistical tests were two sided.

Results: LOH was present in 59% of samples in a cell type–specific manner, highest in serous (72%) and endometrioid (75%) subtypes, but absent in clear cell tumors. LOH was significantly correlated with tumor stage and grade. In addition, KLF6 expression was decreased in tumors when compared with ovarian surface epithelial cells. In contrast, KLF6-SV1 expression was increased ∼5-fold and was associated with increased tumor grade regardless of LOH status. Consistent with these findings, KLF6 silencing increased cellular and tumor growth, angiogenesis, and vascular endothelial growth factor expression, i.p. dissemination, and ascites production. Conversely, KLF6-SV1 down-regulation decreased cell proliferation and invasion and completely suppressed in vivo tumor formation.

Conclusion: Our results show that KLF6 and KLF6-SV1 are associated with key clinical features of EOC and suggest that their therapeutic targeting may alter ovarian cancer growth, progression, and dissemination.
Genetic and Epigenetic Analysis of the Putative Tumor Suppressor km23 in Primary Ovarian, Breast, and Colorectal Cancers
Authors: Campbell Ian G. , Phillips Wayne A. , Choong David Y.H.
Published: June 2006

Purpose: A very high frequency of somatic mutations in the transforming growth factor-β signaling component km23 has been reported in a small series of ovarian cancers (8 of 19, 42%). Functional studies showed that some mutations disrupt km23 function, resulting in aberrant transforming growth factor-β signaling and presumably enhanced tumorigenicity. If verified, this would elevate mutation of km23 as the single most frequent somatic event in ovarian cancer.

Experimental Design: We sought to verify the frequency of silencing of km23 among 104 primary ovarian cancers (49 serous, 18 mucinous, 29 endometrioid/clear cell, and 8 undifferentiated) as well as 72 breast and 61 colorectal cancers by undertaking both somatic mutation and promoter methylation analyses. All four exons of km23 were individually amplified from genomic DNA with primers complementary to surrounding intronic sequences and analyzed by single-stranded conformational polymorphism analysis.

Results: Two germ line polymorphisms were identified, but none of the 237 tumors analyzed harbored somatic km23 mutations. In addition, promoter methylation analysis showed that in all cases, the 5′ CpG island was unmethylated.

Conclusions: Our data suggest that silencing of km23, either through somatic genetic mutation or promoter hypermethylation, is rare in ovarian, breast, and colorectal cancers.
Phosphatidylinositol 3-Kinase in the G Protein-Coupled Receptor–Induced Chemokinesis and Chemotaxis of MDA-MB-468 Breast Carcinoma Cells: A Comparison with Leukocytes
Authors: Bastian Philipp , Posch Birte , Lang Kerstin , Niggemann Bernd , Zaenker Kurt S. , Hatt Hanns , Entschladen Frank
Published: June 2006

The polarization of tumor cells and leukocytes into a front end and a rear end is a crucial prerequisite for their autonomous, directed movement. Phosphatidylinositol 3-kinase (PI3K) is assumed to play an important role in this polarization process, whereas the results obtained with different cell types and different migration assays widely vary. Thus, we conducted a comparative study on the role of the PI3K in the locomotor activity and directionality of the migration of tumor cells on the example of MDA-MB-468 breast carcinoma cells in comparison with CTLs and neutrophil granulocytes. We used our well-established, collagen-based, three-dimensional migration assay for the investigation of the chemokinesis and chemotaxis of these cells. Our results show that the role of the PI3K in the regulation of migratory activity is distinct between the investigated cell types: the migration of CTLs and MDA-MB-468 cells was impaired by the inhibition of the PI3K with wortmannin, whereas neutrophil granulocytes were only slightly affected. However, neither cell type was impaired in the ability to respond chemotactically to gradients of ligands to G protein-coupled receptors. Thus, the PI3K contributes to the regulation of migratory activity but not to the directionality of migration of MDA-MB-468 breast carcinoma cells. As a further conclusion with regard to cancer treatment, the PI3K is not a suitable target for the inhibition of metastasis formation, because the migration of leukocytes is also affected, which leads to a dysfunction of the immune defense. (Mol Cancer Res 2006;4(6):411–21)
Roles of Equatorial Waves and Western Boundary Reflection in the Seasonal Circulation of the Equatorial Indian Ocean
Authors: Yuan Dongliang , Han Weiqing
Published: June 2006

An ocean general circulation model (OGCM) is used to study the roles of equatorial waves and western boundary reflection in the seasonal circulation of the equatorial Indian Ocean. The western boundary reflection is defined as the total Kelvin waves leaving the western boundary, which include the reflection of the equatorial Rossby waves as well as the effects of alongshore winds, off-equatorial Rossby waves, and nonlinear processes near the western boundary. The evaluation of the reflection is based on a wave decomposition of the OGCM results and experiments with linear models. It is found that the alongshore winds along the east coast of Africa and the Rossby waves in the off-equatorial areas contribute significantly to the annual harmonics of the equatorial Kelvin waves at the western boundary. The semiannual harmonics of the Kelvin waves, on the other hand, originate primarily from a linear reflection of the equatorial Rossby waves. The dynamics of a dominant annual oscillation of sea level coexisting with the dominant semiannual oscillations of surface zonal currents in the central equatorial Indian Ocean are investigated. These sea level and zonal current patterns are found to be closely related to the linear reflections of the semiannual harmonics at the meridional boundaries. Because of the reflections, the second baroclinic mode resonates with the semiannual wind forcing; that is, the semiannual zonal currents carried by the reflected waves enhance the wind-forced currents at the central basin. Because of the different behavior of the zonal current and sea level during the reflections, the semiannual sea levels of the directly forced and reflected waves cancel each other significantly at the central basin. In the meantime, the annual harmonic of the sea level remains large, producing a dominant annual oscillation of sea level in the central equatorial Indian Ocean. The linear reflection causes the semiannual harmonics of the incoming and reflected sea levels to enhance each other at the meridional boundaries. In addition, the weak annual harmonics of sea level in the western basin, resulting from a combined effect of the western boundary reflection and the equatorial zonal wind forcing, facilitate the dominance by the semiannual harmonics near the western boundary despite the strong local wind forcing at the annual period. The Rossby waves are found to have a much larger contribution to the observed equatorial semiannual oscillations of surface zonal currents than the Kelvin waves. The westward progressive reversal of seasonal surface zonal currents along the equator in the observations is primarily due to the Rossby wave propagation.
On Science-Practice Integration in Everyday Life
Authors: Murdock Nancy L.
Published: June 2006

Counseling psychologists generally agree that science-practice integration is a good thing. However, most discussions of this topic are less clear about how to actually apply scientific findings to an individual client case. In this article, the author attempts to describe a philosophy for applying research to practice in counseling psychology that requires using theory as the bridge between science and practice.
Social Conflict and the Effectiveness of Aggregate Demand Management Policies
Authors: Tsakalotos Euclid
Published: June 2006

This article examines the role of social conflict in explaining macroeconomic phenomena and, especially, the effectiveness of aggregate demand policies as a means of raising real output. The social conflict approach is compared with a traditional Keynesian view along with Ball, Mankiw, and Romer's and Lucas's models of the determinants of the effectiveness of aggregate demand policies. Empirical analysis during the period from the 1950s to the 1990s for fifteen OECD countries provides significant evidence that the social conflict view of inflation has much to offer in explaining differences in the effectiveness of aggregate demand policies both across countries and through time.
The Hidden Face of Endogenous Growth Theory: Analytical and Ideological Perspectives in the Era of Neoliberal Globalization
Authors: Herrera Rémy
Published: June 2006

The endogenous growth models are generally presented as (1) a macrodynamic version of Walras's general equilibrium, with microeconomic bases; (2) a break with Solow's representation, which proved incapable of explaining growth; (3) identifying present motors of technical progress and growth by mobilizing notions of knowledge, externalities, and increasing returns; (4) rehabilitating state intervention, particularly in social areas (research, education, etc.); and (5) closing the gap between neoclassical authors and heterodox issues. These positions, on which a consensus has been built, are erroneous. The aim of this article is to contribute to the critique of these models by throwing light on their hidden face, especially on the ambiguities surrounding the state's role in the era of neoliberal globalization.
A Reexamination of the Quantitative Issues in the New Interpretation
Authors: Rieu Dong-Min
Published: June 2006

This article evaluates the new interpretation (NI) of Marxian value theory consistent with its inherent logic. The problem of double counting will be examined thoroughly. The relationship between the NI's value of labor power and bundle of wage goods will also be discussed. While the NI generally emphasizes aggregate variables, this article will demonstrate that its inherent logic implies a specific quantitative relationship on the micro level between value and price.
Ecological Predictors of Traumatic Stress Symptoms in Caucasian and Ethnic Minority Children Exposed to Intimate Partner Violence
Authors: Graham-Bermann Sandra A. , DeVoe Ellen R. , Mattis Jacqueline S. , Lynch Shannon , Thomas Shirley A.
Published: June 2006

Traumatic stress symptoms were assessed for 218 children ages 5 to 13 following exposure to intimate partner violence: 33% of Caucasian and 17% of minority children were diagnosed with posttraumatic stress disorder. A risk and protective factors model was used to predict traumatic stress symptoms. For Caucasian children, the best predictors were mothers’ mental health and low self-esteem. For minority children, the amount of violence, mothers’ low self-esteem, and low income predicted traumatic stress. Social support to the mother, inclusive of friends, relatives, and religion, was a protective element. Implications for assessment and intervention are discussed in light of each group’s experiences.
Regulation of airway smooth muscle RhoA/ROCK activities by cholinergic and bronchodilator stimuli
Authors: Liu C. , Zuo J. , Janssen L. J.
Published: June 2006

The current study set out to compare the temporal relationships of Rho activity, Rho kinase (ROCK) activity and tone following cholinergic stimulation in the presence and absence of three different bronchodilators.

Bovine trachea challenged with a half-maximally effective concentration of carbachol (CCh) was flash-frozen at different times, then assayed for Rho (rhotekin pull-down assay) and ROCK (Western blot; radiometric assay) activities.

Rho was activated within 30 s, followed by ROCK (peak at 2 min); both returned to baseline by 20 min, although tone continued to rise over that period. Increasing the concentration of CCh greatly increased the magnitudes and rates of stimulation of Rho, ROCK and tone. These CCh-induced changes were next compared in tissues pre-treated with isoproterenol, salmeterol or the nitric oxide donorS-nitroso-N-acetylpenicillamine (SNAP). Neither the time course nor the magnitude of Rho-activation were reduced by the β-agonists; SNAP slowed Rho activation but it did not alter the peak magnitude. These observations were mirrored in ROCK activation and contraction. When tissues were pre-constricted with CCh and then challenged with the bronchodilators, however, all three agonists reversed cholinergically stimulated Rho, ROCK and myosin light chain kinase activities as well as tone.

In conclusion, bronchodilators can suppress RhoA and Rho kinase activities, although their major effect appears to be on myosin light chain kinase activity.
The effects of socioeconomic status, accessibility to services and patient type on hospital use in Western Australia: a retrospective cohort study of patients with homogenous health status
Authors: Moorin Rachael E , Holman C D'Arcy J
Published: June 2006

Background

This study aimed to investigate groups of patients with a relatively homogenous health status to evaluate the degree to which use of the Australian hospital system is affected by socio-economic status, locational accessibility to services and patient payment classification.

Method

Records of all deaths occurring in Western Australia from 1997 to 2000 inclusive were extracted from the WA mortality register and linked to records from the hospital morbidity data system (HMDS) via the WA Data Linkage System. Adjusted incidence rate ratios of hospitalisation in the last, second and third years prior to death were modelled separately for five underlying causes of death.

Results

The independent effects of socioeconomic status on hospital utilisation differed markedly across cause of death. Locational accessibility was generally not an independent predictor of utilisation except in those dying from ischaemic heart disease and lung cancer. Private patient status did not globally affect utilisation across all causes of death, but was associated with significantly decreased utilisation three years prior to death for those who died of colorectal, lung or breast cancer, and increased utilisation in the last year of life in those who died of colorectal cancer or cerebrovascular disease.

Conclusion

It appears that the Australian hospital system may not be equitable since equal need did not equate to equal utilisation. Further it would appear that horizontal equity, as measured by equal utilisation for equal need, varies by disease. This implies that a 'one-size-fits-all' approach to further improvements in equity may be over simplistic. Thus initiatives beyond Medicare should be devised and evaluated in relation to specific areas of service provision.
Sexually transmitted Human Papillomavirus type variations resulting in high grade cervical dysplasia in North-East North Dakota and North-West Minnesota
Authors: Balakrishnan Lata , Clauson Ryan , Weiland Timothy , Bianco Michelle , Milavetz Barry
Published: June 2006

Background

A review of Pap smear diagnoses from a reference laboratory in Grand Forks, North Dakota over a 3-year period (07/00 to 10/03) revealed a two-fold higher rate of high grade squamous intraepithelial lesion in a community in northwest Minnesota (Roseau, 0.486%) than in northeast North Dakota (Grand Forks, 0.249%), in spite of both having similar rates of low-grade squamous intraepithelial lesion (1.33% vs.1.30% respectively)

Objectives

To identify the different types of HPV present in patient populations showing high-grade dysplasia in Grand Forks, ND and Roseau, MN.

Study design

Formaldehyde-fixed paraffin-embedded cervical tissue samples were analyzed using polymerase chain reaction (PCR) to detect the presence of HPV type 16, 18 and 31.

Results

Our studies showed that 41 % of samples from Roseau were triply infected with HPV serotypes 16, 18 and 31 in comparison to 12 % from Grand Forks.

Conclusion

Due to the small sample size we were unable to prove the study to be statistically significant. However, our results suggest that the presence of HPV 16, 18 and 31 in triply infected samples may be the cause of the higher percentage of high-grade dysplasia in Roseau, MN when compared to Grand Forks, ND.
A key role for the HLH transcription factor EBF2COE2,O/E-3 in Purkinje neuron migration and cerebellar cortical topography
Authors: Croci Laura , Chung Seung-Hyuk , Masserdotti Giacomo , Gianola Sara , Bizzoca Antonella , Gennarini Gianfranco , Corradi Anna , Rossi Ferdinando , Hawkes Richard , Consalez G. Giacomo
Published: June 2006

Early B-cell factor 2 (EBF2) is one of four mammalian members of an atypical helix-loop-helix transcription factor family (COE). COE proteins have been implicated in various aspects of nervous and immune system development. We and others have generated and described mice carrying a null mutation of Ebf2, a gene previously characterized in the context of Xenopus laevis primary neurogenesis and neuronal differentiation. In addition to deficits in neuroendocrine and olfactory development, and peripheral nerve maturation, Ebf2 null mice feature an ataxic gait and obvious motor deficits associated with clear-cut abnormalities of cerebellar development. The number of Purkinje cells (PCs) in the Ebf2 null is markedly decreased, resulting in a small cerebellum with notable foliation defects,particularly in the anterior vermis. We show that this stems from the defective migration of a molecularly defined PC subset that subsequently dies by apoptosis. Part of the striped cerebellar topography is disrupted due to cell death and, in addition, many of the surviving PCs, that would normally adopt a zebrin II-negative phenotype, transdifferentiate to Zebrin II-positive, an unprecedented finding suggesting that Ebf2 is required for the establishment of a proper cerebellar cortical map.
Electrochemistry and Characterization of Conducting Poly(3-methylthiophene) Electrodes Containing Ferrocene Moieties
Authors: Galal Ahmed , Atta Nada F , Darwish Soher A , Abdallah AbuBakr M
Published: June 2006

Ferrocenium hexafluorophosphate was used as the supporting electrolyte during the electropolymerization of poly(3-methylthiophene) and poly(1-methylpyrrole). The electrochemical behavior of the resulting polymer electrode indicated the incorporation of the ferrocenium moiety in the polymer film. The appearance and the magnitudes of the voltammetric anodic and cathodic current peaks of the ferrocenium/ferrocenium+ couples were influenced by: (I) the method of ferrocene incorporation into the polymer film, (ii) the concentration of both the ferrocenium and the supporting electrolyte used during the polymer deposition, (iii) the thickness of the polymer film, and (iv) the type of electrolyte used during the polymer film electrochemical characterization. FTIR experiments were performed on polymer films containing the ferrocenecarbaldehyde. The results were compared to the spectrum of ferrocene-free film; the comparison indicated the incorporation of the ferrocene moiety within the polymer film. The structural aspects of the polymer films were studied using XPS experiments, which indicated the presence of iron for films containing ferrocenium. The morphological aspects of the films were studied by SEM technique which indicated that “ferrocenium-free” film morphologies are similar to those of “ferrocenium-containing” films. A model for the charge transfer within the polymer film is described. The method described in this work resulted in a stable ferrocenium-bound to the polymeric film.
Substituent Effect of 1,4-Benzenedicarbonitriles as Sensitizers on the Photoinduced Electron Transfer Reactions in Alcohol
Authors: Suzuki Masanori , Ikeno Taketo , Osoda Kazuhiko , Narasaka Koichi , Suenobu Tomoyoshi , Fukuzumi Shunichi , Ishida Akito
Published: June 2006

In the photosensitized electron transfer reaction of 6,6-diphenyl-1,4-dioxaspiro[4.5]decane in methanol (MeOH), the quantum yield is increased by the use of 2-methylbenzene-1,4-dicarbonitrile (2-methyl-BDC) or 2,5-dimethylbenzene-1,4-dicarbonitrile (2,5-dimethyl-BDC) as compared to that by the use of 1,4-benzenedicarbonitrile (BDC), though the excited methyl-substituted BDCs have lower reduction potentials than the excited BDC. Detailed study on this substituent effect reveals that the electron transfer between MeOH and the excited BDC occurs to some extent. By the use of methylated BDCs, electron transfer between the excited sensitizers and MeOH is suppressed enough due to its lower reduction potential. Some typical photoinduced electron transfer reactions in alcohol proceed more efficiently by the use of 2-methyl-BDC or 2,5-dimethyl-BDC instead of BDC.
Preparation of Electronically Conducting Ultra-Thin Polymer Films
Authors: Cho Gyoujin
Published: June 2006

Admicellar polymerization uses adsorbed surfactant aggregates to concentrate monomeric species at the solution–solid interface and to localize the polymer-forming reaction over a surface. The process has been adapted for the deposition of polypyrrole thin films on mica substrates. Amphiphiles adsorb from aqueous solution onto mica substrates and form self-assembled arrays. These arrays have been characterized by atomic force microscopy (AFM). Polypyrrole films prepared by polymerization in the self-assembled arrays (PSAA) were characterized and compared with samples made by polymerization in the absence of self-assembled arrays (surface nucleation, PSN). Images and measurements by AFM indicate that PSAA films over mica surfaces tend to be much smoother than PSN layers at the same condition. The ultra-thin PSAA (130 nm) can be fabricated simply, controlled by changing the ratio between water, surfactant, and pyrrole concentration under ambient conditions. Although thinner, PSAA films have more stable and higher conductivity than the PSN films. The relationship between film morphology and electronic properties has been discussed.
X-Ray Photoelectron Spectroscopic Study of Alternately Layered Zirconium and Hafnium Phosphonate Thin Films on Silicon Substrates
Authors: Umemura Yasushi , Yamagishi Akihiko , Tanaka Ken-ichi
Published: June 2006

Multilayer films of alternately layered zirconium and hafnium phosphonates on silicon substrates were prepared and characterized by X-ray photoelectron spectroscopy. It is revealed that the multilayer film is built up layer-by-layer in the repeated order of a zirconium phosphonate layer and a hafnium phosphonate layer. The relative peak intensity of the Zr 3d line to the Hf 4d5/2 line in the photoelectron spectra of the film takes a lower value as the take-off angle between the surface normal and the detector (α) increases. The mean free path of a photoelectron with an energy of ca. 1000 eV was estimated to be 70—90 Å in the film by analyzing the α dependence of the relative peak intensities.
A Chemo-Enzymatic Synthesis of d-Allosamine Derivatives from Tri-O-acetyl-d-glucal
Authors: Sugai Takeshi , Okazaki Hanako , Kuboki Atsuhito , Ohta Hiromichi
Published: June 2006

N-Acetyl-d-allosamine and its derivatives were synthesized from tri-O-acetyl-d-glucal based on lipase-catalyzed selective protection of primary alcohols, [3,3] sigmatropic rearrangement of allylic trichloroacetimidates, and stereoselective ruthenium-catalyzed dihydroxylation. In the course of this study, it was revealed that the Pseudomonas lipase-catalyzed acetylation occurred in a high yield (> 90%) exclusively at the primary alcohols of three Ferrier rearrangement products derived from tri-O-acetyl-d-glucal.
Phthalocyanines Containing Silicons in Their Peripheral Substituent Groups
Authors: Kobayashi Nagao , Higashi Ryuji , Tomura Tatsuya
Published: June 2006

Some phthalonitriles and 1H-isoindole-1,3(2H)-diimines containing silicon(s) in their alkoxy substituent groups are prepared and used for phthalocyanine formation reactions. Silicon–carbon bonds often survive under the reaction conditions using K2CO3 in N,N-dimethylformamide (DMF), but are often broken in the presence of sodium hydride. Silicons in the alkoxy groups do not affect the electronic absorption spectra of phthalocyanines in solution significantly. The Q band of films of phthalocyanines (Pcs) with alkyl or alkoxy groups attached to benzene carbons furthest from the Pc core lies to the blue compared to the Pcs in solution, while films of Pcs with eight alkoxy groups closest to Pc core have a Q band shifted to the red.
Analysis of Acidic Compounds in Recycle Solvent for Coal Liquefaction
Authors: Miki Yasuo , Sugimoto Yoshikazu
Published: June 2006

Recycle solvents were obtained in 50 d of continuous operation of a 1 ton/day coal-liquefaction plant at Kimitsu. Acidic fractions were obtained by base extraction for the starting solvent and final solvent, and their components were analyzed in detail by gas chromatography/mass spectrometry. The application of a selected ion monitoring technique has allowed the assignment of the atomic compositions to practically all compounds despite many of their presence as overlapping peaks on the chromatogram: 327 individual compounds for 142 peaks.

These compounds have been classified into nine of compound types: phenols, indanols/tetrahydronaphthols, naphthols, biphenylols/acenaphthenols, hexahydroacenaphthylenols, fluorenols, phenanthrenols/anthracenols, phenylnaphthols, and pyrenols/fluoranthenols. As compared to the initial solvent, the final solvent contains higher concentrations of indanols/tetrahydronaphthols and hexahydroacenaphthylenols and contains a lower concentration of pyrenols/fluoranthenols.
Osteoclast Differentiation by RANKL Requires NF-κB-Mediated Downregulation of Cyclin-Dependent Kinase 6 (Cdk6)
Authors: Ogasawara Toru , Katagiri Mika , Yamamoto Aiichiro , Hoshi Kazuto , Takato Tsuyoshi , Nakamura Kozo , Tanaka Sakae , Okayama Hiroto , Kawaguchi Hiroshi
Published: June 2006

This study investigated the involvement of cell cycle factors in RANKL-induced osteoclast differentiation. Among the G1 cell cycle factors, Cdk6 was found to be a key molecule in determining the differentiation rate of osteoclasts as a downstream effector of the NF-κB signaling.

Introduction: A temporal arrest in the G1 phase of the cell cycle is a prerequisite for cell differentiation, making it possible that cell cycle factors regulate not only the proliferation but also the differentiation of cells. This study investigated cell cycle factors that critically influence differentiation of the murine monocytic RAW264.7 cells to osteoclasts induced by RANKL.

Materials and Methods: Growth-arrested RAW cells were stimulated with serum in the presence or absence of soluble RANKL (100 ng/ml). Expressions of the G1 cell cycle factors cyclin D1, D2, D3, E, cyclin-dependent kinase (Cdk) 2, 4, 6, and Cdk inhibitors (p18 and p27) were determined by Western blot analysis. Involvement of NF-κB and c-jun N-terminal kinase (JNK) pathways was examined by overexpressing dominant negative mutants of the IκB kinase 2 (IKKDN) gene and mitogen-activated protein kinase kinase 7 (MKK7DN) gene, respectively, using the adenovirus vectors. To determine the direct effect of Cdk6 on osteoclast differentiation, stable clones of RAW cells transfected with Cdk6 cDNA were established. Osteoclast differentiation was determined by TRACP staining, and cell cycle regulation was determined by BrdU uptake and flow cytometric analysis.

Results and Conclusion: Among the cell cycle factors examined, the Cdk6 level was downregulated by RANKL synchronously with the appearance of multinucleated osteoclasts. Inhibition of the NF-κB pathway by IKKDN overexpression, but not that of the JNK pathway by MKK7DN overexpression, caused the decreases in both Cdk6 downregulation and osteoclastogenesis by RANKL. RAW cells overexpressing Cdk6 resist RANKL-induced osteoclastogenesis; however, cell cycle regulation was not affected by the levels of Cdk6 overexpression, suggesting that the inhibitory effect of Cdk6 on osteoclast differentiation was not exerted through cell cycle regulation. These results indicate that Cdk6 is a critical regulator of RANKL-induced osteoclast differentiation and that its NF-κB-mediated downregulation is essential for efficient osteoclast differentiation.
Die Jakobsleiter, ein aussagenreiches Motiv der Väterliteratur
Authors: Gahbauer OSB Ferdinand R
Published: June 2006

Das Motiv der Jakobsleiter vereinigt drei Momente in sich. Dem Auf- und Absteigen der Boten Gottes eignet Dynamik. Es werden Botschaften von oben nach unten und umgekehrt ausgetauscht. So entsteht Gemeinschaft, auch kirchliche Gemeinschaft zwischen oben und unten und zwischen denen, die auf derselben Sprosse stehen. Das Besteigen der Himmelsleiter birgt Mühe und Gefahr in sich. Wer die Leiter besteigt, setzt sich Mühen und dem Risiko eines Absturzes aus. So ist auch das im Bild der Leiter dargestellte Leben des Asketen reich an Gefahren, da die Macht des Bösen sie mit allen Mitteln zum Absturz bringen will. Andererseits kommt Gott mit reichen Gnadengaben entgegen. Zeichen dafür ist das Kreuz Christi, das die Menschen zu Gott emporhebt. Durch seine Menschwerdung hat sich Gott selbst auf den Weg gemacht. Daher wurde Maria zur Himmelsleiter, auf der sich Gott und Mensch begegnen können. Der heilige Geist ist als erstes Angeld Gottes die Leiter, die zum Aufstieg zu Gott führt. Wenn das Gesetz mit der Leiter verglichen wird, soll dadurch seine auf Christus vorbereitende Bedeutung ausgesagt sein. Schließlich wird auch die Kirche als Himmelsleiter gesehen. Sie verbindet Haupt und Glieder der Kirche miteinander. Die Leiter ist also keine Einbahnstraße, sondern wird zum Bild für die Begegnung zwischen Gott und Mensch und zwischen den Gliedern der Kirche.
Assumptio Carnis and the Ascent to God: Hilary's Revision of Irenaeus' Doctrine of Salus Carnis
Authors: Meyer John R
Published: June 2006

Hilarius De trinitate führt die irenäische Lehre vom solus carnis einen Schritt weiter, besonders im Hinblick auf die eschatologischen Aussichten, die den christlichen Glaubenden erwartet. Die vornehmliche Absicht von Irenaeus in Adversus Haereses war es, den dualistischen Tendenzen verschiedener Formen christlicher Gnosis entgegenzuwirken, und zu diesem Zweck betonte er den Wert der Schöpfung der Materie, einschließlich des menschlichen Körpers bzw. Fleisches. Ein anderer, häufig übersehener Aspekt der Soteriologie des Irenaeus ist die Beobachtung, daß die Welt und die Menschen unvollständig sind. Die endgültige Vollendung des Universums, und die der Menschen im besonderen, ist ein eschatologisches Ereignis, auf das hin alles gerichtet ist. Hilarius nimmt dieses theologische Erbe auf im Angesicht einer neuen und in seinen Augen zerstörerischen Tendenz des Arianismus. Die arianischen und homöischen Autoren des vierten Jahrhunderts argumentierten, daß der Sohn und der Geist nachgeordnete göttliche Geschöpfe seien, die Gott eingesetzt habe, um die Menschheit zu erschaffen und zu retten. Der modus operandi dieser von Hilarius kritisierten Sicht der Erlösung war die moralische Vollkommenheit, wohingegen nach antiarianischer Sicht, die sich im Osten unter der Führung von Athanasius und im Westen unter der von Hilarius formierte, Erlösung mit einer radikalen Vergöttlichung unseres Wesens verbunden war. Während Hilarius nicht ausführlicher über die pneumatische Komponente der Erlösung nachdachte, so benutzte er doch Einsichten von Irenaeus und Athanasius, um eine erneuerte paulinische Perspektive zu präsentieren: die Vergöttlichung oder Verherrlichung des Christen im auferstandenen Körper des verherrlichten Christus. Man kann sogar behaupten, daß Hilarius ein wichtigerer Vertreter der von Paulus stammenden und latent präsenten Vorstellung eines „mystischen Körpers Christi“ war, als gemeinhin anerkannt wird.
A Church Historian in Search of an Identity: Aspects of Early Byzantine Palestine in Sozomen's Historia Ecclesiastica
Authors: Argov Eran I
Published: June 2006

Die jüngsten Studien zu spätantiker Geschichtsschreibung werfen neues Licht auf die Gattung der Kirchengeschichte. Traditionelle Einstellungen zu den Kirchenhistorikern des fünften Jahrhunderts, nämlich Sokrates von Konstantinopel, Sozomenus von Bethelia und Theodoretus von Cyrrhus, vor allem als Fortsetzer und Nachahmer des Euseb von Caesarea, haben Raum gemacht für eine subtilere Annäherung, indem jedes einzelne Werk dieser Autoren individuell untersucht und nach seinem inneren Wert beurteilt wird.

Dieser Aufsatz hebt einen besonderen Grundzug der Historia Ecclesiastica des Sozomenus hervor: die Bearbeitung seines heimatlichen Palästinas, welches er innerhalb seines Werkes in drei verschiedenen, untereinander verbundenen Kontexten erörtert: Familie, Politik und Religion. Die vorliegende Auffassung des Berichtes seiner heimatlichen Region legt nahe, daß die Christianisierung Palästinas in der frühbyzantinischen Epoche das Hervortreten eines eindeutig palästinischen kollektiven Identitätsgefühls bewirkt hat.