bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcitonin Stimulates Multiple Stages of Angiogenesis by Directly Acting on Endothelial Cells
Authors: Chigurupati Srinivasulu , Kulkarni Trupti , Thomas Shibu , Shah Girish
Published: September 2005

Although a strong correlation between neuroendocrine differentiation and angiogenesis of prostate cancer has been reported, no mechanistic link between the two events has been established. Because neuropeptide calcitonin is secreted by prostate tumors and endothelial cells are known to express calcitonin receptor–like receptor, we examined the potential action of calcitonin on endothelial cells. The presence of calcitonin receptor, calcitonin receptor–like receptor, and receptor activity–modifying proteins in human microvessel endothelial-1 cells was tested by reverse transcriptase-PCR (RT-PCR). The proangiogenic action of calcitonin was examined in several in vitro models of angiogenesis using HMEC-1 cells and also in vivo using dorsal skinfold assays. Calcitonin expression of PC-3M cells was modulated, and its effect on angiogenesis was examined in in vitro as well as in vivo models. The results of RT-PCR and radioligand receptor assays showed the presence of functional calcitonin receptor in HMEC-1 cells. Calcitonin stimulated all phases of angiogenesis through the calcitonin receptor, but its effect on tube morphogenesis by endothelial cells occurred at the concentration of the Kd of calcitonin receptor. Silencing of calcitonin receptor expression in HMEC-1 cells abolished calcitonin-induced tube formation. Vascular endothelial growth factor antibodies attenuated but did not abolish calcitonin-induced tube morphogenesis. PC-3M prostate cancer cells induced angiogenesis in in vivo and in vitro models. Overexpression of calcitonin in PC-3M cells increased their angiogenic activity, whereas the silencing of calcitonin expression abolished it. These results show that prostate tumor–derived calcitonin may play an important role in prostate tumor growth by regulating intratumoral vascularization.
Lung Cancer Susceptibility in Fhit-Deficient Mice Is Increased by Vhl Haploinsufficiency
Authors: Zanesi Nicola , Mancini Rita , Sevignani Cinzia , Vecchione Andrea , Kaou Mohamed , Valtieri Mauro , Calin George A. , Pekarsky Yuri , Gnarra James R. , Croce Carlo M. , Huebner Kay
Published: September 2005

The FHIT gene plays important roles in cancer development, including lung cancers, in which the Fhit protein is frequently lost. To determine if Fhit-deficient mice exhibit increased susceptibility to carcinogen-induced lung cancer, mice were treated with the pulmonary carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone. Wild-type and Fhit-deficient animals did not exhibit significantly different frequencies of lung lesions, but Fhit−/− mice showed significantly increased average tumor volume (1.62 mm3) and multiplicity in tumor-bearing mice, compared with wild-type mice (0.70 mm3). Tumors of Fhit−/− mice were all carcinomas, whereas Fhit+/+ mice did not develop carcinomas. To determine if Fhit absence, in combination with deficiency of an additional 3p tumor suppressor, would affect the frequency of tumor induction, we examined the spontaneous and dimethylnitrosamine-induced tumor phenotype of Fhit−/−Vhl+/− mice. Whereas no spontaneous lung tumors were observed in Fhit−/− or Vhl+/− mice, 44% of Fhit−/−Vhl+/− mice developed adenocarcinomas by 2 years of age. Dimethylnitrosamine (6 mg/kg body weight) induced lung tumors (adenomas and carcinomas) in 100% of Fhit−/−Vhl+/− mice and adenomas in 40% of Fhit−/− mice by 20 months of age. Thus, double deficiency in murine homologues of 3p suppressor genes, including haploinsufficiency of Vhl, predisposes to spontaneous and induced lung cancers, showing that Fhit-deficient mice will be useful, in combination with other 3p tumor suppressors, in recapitulating a pattern of lung cancer development similar to the human pattern; such double- or triple-deficient mice will be excellent lung cancer prevention and therapy models.
Genistein, a Dietary Isoflavone, Down-Regulates the MDM2 Oncogene at Both Transcriptional and Posttranslational Levels
Authors: Li Mao , Zhang Zhuo , Hill Donald L. , Chen Xinbin , Wang Hui , Zhang Ruiwen
Published: September 2005

Although genistein has chemopreventive effects in several human malignancies, including cancers of the breast, colon, and prostate, the mechanisms of action are not fully understood. Herein we report novel mechanisms whereby genistein down-regulates the MDM2 oncogene, perhaps explaining some of its anticancer activities. In a dose- and time-dependent manner, genistein reduced MDM2 protein and mRNA levels in human cell lines of breast, colon, and prostate cancer; primary fibroblasts; and breast epithelial cells. The inhibitory effects were found at both transcriptional and posttranslational levels and were independent of tyrosine kinase pathways. We found that the NFAT transcription site in the region between −132 and +33 in the MDM2 P2 promoter was responsive to genistein. At the posttranslational level, genistein induced ubiquitination of MDM2, which led to its degradation. Additionally, genistein induced apoptosis and G2 arrest and inhibited proliferation in a variety of human cancer cell lines, regardless of p53 status. We further showed that MDM2 overexpression abrogated genistein-induced apoptosis in vitro and that genistein inhibited MDM2 expression and tumor growth in PC3 xenografts. In conclusion, genistein directly down-regulates the MDM2 oncogene, representing a novel mechanism of its action that may have implications for its chemopreventive and chemotherapeutic effects.
ErbB3 Expression Predicts Tumor Cell Radiosensitization Induced by Hsp90 Inhibition
Authors: Dote Hideaki , Cerna David , Burgan William E. , Camphausen Kevin , Tofilon Philip J.
Published: September 2005

The ability to identify tumors that are susceptible to a given molecularly targeted radiosensitizer would be of clinical benefit. Towards this end, we have investigated the effects of a representative Hsp90 inhibitor, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17DMAG), on the radiosensitivity of a panel of human tumor cell lines. 17DMAG was previously shown to enhance the radiosensitivity of a number of human cell lines, which correlated with the loss of ErbB2. We now report on cell lines in which 17DMAG induced the degradation of ErbB2, yet had no effect on radiosensitivity. In a comparison of ErbB family members, ErbB3 protein was only detectable in cells resistant to 17DMAG-induced radiosensitization. To determine whether ErbB3 plays a casual role in this resistance, short interfering RNA (siRNA) was used to knockdown ErbB3 in the resistant cell line AsPC1. Whereas individual treatments with siRNA to ErbB3 or 17DMAG had no effect on radiosensitivity, the combination, which reduced both ErbB2 and ErbB3, resulted in a significant enhancement in AsPC1 radiosensitivity. In contrast to siRNA to ErbB3 or 17DMAG treatments only, AsPC1 cell exposure to the combination also resulted in a decrease in ErbB1 kinase activity. These results indicate that ErbB3 expression predicts for tumor cell susceptibility to and suggests that the loss of ErbB1 signaling activity is necessary for 17DMAG-induced radiosensitization. However, for cell lines sensitized by 17DMAG, treatment with siRNA to ErbB2, which reduced ErbB1 activity, had no effect on radiosensitivity. These results suggest that, whereas the loss of ErbB1 signaling may be necessary for 17DMAG-induced radiosensitization, it is not sufficient.
Five Loci, SLT1 to SLT5, Controlling the Susceptibility to Spontaneously Occurring Lung Cancer in Mice
Authors: Wang Daolong , You Ming
Published: September 2005

A series of linkage studies was previously conducted to identify quantitative trait loci associated with chemically induced lung tumors. However, little is known of genetic susceptibility to spontaneously occurring lung tumorigenesis (SLT) in mice. In this study, we did a whole-genome linkage disequilibrium analysis for susceptibility to SLT in mice using ∼135,900 single-nucleotide polymorphisms (SNPs) from the Roche and Genomic Institute of the Novartis Research Foundation SNP databases. A common set of 13 mouse strains was used, including 10 resistant strains (129X1/SvJ, AKR/J, C3H/HeJ, C57BL/6J, DBA/2J, NZB/BlnJ, CAST/EiJ, SPRET/EiJ, SM/J, and LP/J) and 3 susceptible strains (A/J, BALB/cJ, and NZW/LaCJ). Fisher exact test was used to assess the association between individual SNPs and susceptibility to SLT. Five regions, SLT1 to SLT5, were mapped on chromosomes 6, 7, 8, 19, and X, respectively. SLT1 to SLT5 showed a significant association with SLT under the empirical threshold (P ≤ 0.004) derived from permutation tests. SNP versus SNP association tests indicated that these SLT regions were unlikely to be caused by population substructure. Thus, SLT1 to SLT5 seem to be novel loci controlling the susceptibility to spontaneously occurring lung cancer in mice. Our results provide, for the first time, an insight into the genetic control of spontaneously occurring lung tumorigenesis.
Mice Expressing a Mammary Gland–Specific R270H Mutation in the p53 Tumor Suppressor Gene Mimic Human Breast Cancer Development
Authors: Wijnhoven Susan W.P. , Zwart Edwin , Speksnijder Ewoud N. , Beems Rudolf B. , Olive Kenneth P. , Tuveson David A. , Jonkers Jos , Schaap Mirjam M. , van den Berg Jolanda , Jacks Tyler , van Steeg Harry , de Vries Annemieke
Published: September 2005

The tumor suppressor gene p53 has an apparent role in breast tumor development in humans, as ∼30% of sporadic tumors acquire p53 mutations and Li-Fraumeni syndrome patients carrying germ line p53 mutations frequently develop breast tumors at early age. In the present study, conditional expression of a targeted mutation is used to analyze the role of the human R273H tumor-associated hotspot mutation in p53 in mammary gland tumorigenesis. Heterozygous p53R270H/+WAPCre mice (with mammary gland–specific expression of the p53.R270H mutation, equivalent to human R273H, at physiologic levels) develop mammary tumors at high frequency, indicating that the R270H mutation predisposes for mammary gland tumor development and acts in a dominant-negative manner in early stages of tumorigenesis. Spontaneous tumor development in these mice is further accelerated by 7,12-dimethylbenz(a)anthracene (DMBA) treatment at young age. The majority of spontaneous and DMBA-induced carcinomas and sarcomas from p53R270H/+WAPCre mice is estrogen receptor α positive, and expression profiles of genes also implicated in human breast cancer appear similarly altered. As such, p53R270H/+WAPCre mice provide a well-suited model system to study the role of p53 in breast tumorigenesis and the responsiveness of mammary gland tumors to chemotherapeutics.
Bcl-2 Antisense Oligonucleotide Overcomes Resistance toE1AGene Therapy in a Low HER2-Expressing Ovarian Cancer Xenograft Model
Authors: Bartholomeusz Chandra , Itamochi Hiroaki , Yuan Linda X.H. , Esteva Francisco J. , Wood Christopher G. , Terakawa Naoki , Hung Mien-Chie , Ueno Naoto T.
Published: September 2005

We are currently conducting clinical trials of E1A gene therapy for patients with ovarian cancer. The adenovirus type 5 E1A gene suppresses growth of ovarian cancer cells that overexpress HER-2/neu (HER2) and growth of some—but not all—that express low HER2. In HER2-overexpressing cells, suppression by E1A is predominantly by down-regulation of HER2, but the mechanism in low HER2-expressing cells is not fully understood. The adenoviral E1B protein has sequential and functional homology to Bcl-2 and prolongs the viability of adenovirus host cells by inhibiting E1A-induced apoptosis. Bcl-2 is overexpressed in ovarian cancer and participates in chemoresistance; we hypothesized that Bcl-2 inhibits E1A-induced apoptosis leading to resistance to E1A gene therapy. E1A suppressed colony formation of ovarian cancer cells that express low levels of Bcl-2 and HER2 (OVCAR-3 and OVCA 433), but enhanced colony formation in low HER2-, high Bcl-2–expressing ovarian cancer cells (2774 and HEY). Treating 2774 or HEY cells with antisense oligonucleotide Bcl-2 (Bcl-2-ASO) did not reduce cell viability. E1A combined with Bcl-2-ASO led to significant decreases in cell viability resulting from increased apoptosis relative to cells treated with E1A alone (P < 0.05). The increase in apoptosis was partly due to cytochrome c release and subsequently caspase-9 activation by Bcl-2-ASO. Finally, in an ovarian cancer xenograft model, treatment with Bcl-2-ASO did not prolong survival, but E1A plus Bcl-2-ASO did (P < 0.001). In conclusion, ovarian tumors overexpressing Bcl-2 may not respond well to E1A gene therapy, but treatment with a combination of E1A and Bcl-2-ASO may overcome this resistance.
Epidermal Growth Factor Induces WISP-2/CCN5 Expression in Estrogen Receptor-α-Positive Breast Tumor Cells through Multiple Molecular Cross-talks
Authors: Banerjee Snigdha , Sengupta Krishanu , Saxena Neela K. , Dhar Kakali , Banerjee Sushanta K.
Published: September 2005

Epidermal growth factor (EGF) is a mitogen for estrogen receptor (ER)–positive breast tumor cells, and it has been proven that EGF occasionally mimicked estrogen action and cross-talks with ER-α to exert its activity. Therefore, the present study was undertaken to explore whether EGF is able to modulate the expression of Wnt-1-induced signaling protein-2/connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed 5 (WISP-2/CCN5), an estrogen-responsive gene, in normal and transformed cell lines of the human breast and, if so, whether this induction is critical for EGF mitogenesis and what downstream signaling pathways are associated with this event. Here, we show that EGF-induced WISP-2 expression in ER- and EGF receptor–positive noninvasive MCF-7 breast tumor cells was dose and time dependent and that expression was modulated at transcription level. A synergism was seen in combination with estrogen. Moreover, small interfering RNA–mediated inhibition of WISP-2/CCN5 activity in MCF-7 cells resulted in abrogation of proliferation by EGF. The multiple molecular cross-talks, including the interactions between phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase signaling pathways and two diverse receptors (i.e., ER-α and EGFR), were essential in the event of EGF-induced WISP-2/CCN5 up-regulation in MCF-7 cells. Moreover, EGF action on WISP-2/CCN5 is restricted to ER- and EGFR-positive noninvasive breast tumor cells, and this effect of EGF cannot be instigated in ER-α-negative and EGFR-positive normal or invasive breast tumor cells by introducing ER-α. Finally, regulation of phosphorylation of ER-α and EGFR may play critical roles in EGF-induced transcriptional activation of WISP-2 gene in breast tumor cells.
Contribution of Epigenetic Silencing of Tumor Necrosis Factor–Related Apoptosis Inducing Ligand Receptor 1 (DR4) to TRAIL Resistance and Ovarian Cancer
Authors: Horak Peter , Pils Dietmar , Haller Griet , Pribill Ingrid , Roessler Max , Tomek Sandra , Horvat Reinhard , Zeillinger Robert , Zielinski Christoph , Krainer Michael
Published: September 2005

Dysregulation of apoptosis may support tumorigenesis by allowing cells to live beyond their normally intended life span. The various receptors for tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) are located on chromosome 8p21.2, a region frequently deleted in ovarian cancer. Lack of expression of TRAIL receptor 1 (death receptor 4, DR4) correlates with resistance to TRAIL-induced apoptosis in ovarian cancer cells. Reconstitution of DR4 in the TRAIL-resistant A2780 ovarian cancer cell line was investigated with the demethylating agent 5-aza-2′-deoxycytidine and transient gene transfer. Regulation of other genes in the TRAIL pathway by 5-aza-2′-deoxycytidine was assessed in DNA GeneChip experiments. Primary ovarian cancers were analyzed by methylation-specific PCR and immunohistochemical analysis of a tissue microarray. Regulation of DR4 expression by demethylation or transient transfection is of functional relevance for TRAIL resistance in an ovarian cancer cell line. Hypermethylation of the DR4 promoter could be found in 10 of 36 (27.7%) DNAs isolated from ovarian cancer tissue. In an independent set of 68 ovarian cancer cases, a complete loss or down-regulation of DR4 protein expression was observed 10.3% and 8.8% patients, respectively. A significant (P = 0.019) majority of these patients was below 50 years of age. Our findings show a functional relevance of the level of DR4 expression in ovarian cancer and suggest a substantial contribution of DR4 hypermethylation and consequent loss of DR4 expression to ovarian cancer pathogenesis, particularly in premenopausal patients.
Allelic Imbalance in Primary Breast Carcinomas and Metastatic Tumors of the Axillary Lymph Nodes
Authors: Ellsworth Rachel E. , Ellsworth Darrell L. , Neatrour David M. , Deyarmin Brenda , Lubert Susan M. , Sarachine Miranda J. , Brown Patrick , Hooke Jeffrey A. , Shriver Craig D.
Published: September 2005

Axillary lymph node status is the most important prognostic factor in predicting disease outcome in women with breast cancer. A number of chromosomal aberrations in primary breast tumors have been correlated with lymph node status and clinical outcome, but chromosomal changes particular to metastatic lymph node tumors have not been well studied. DNA samples isolated from laser-microdissected primary breast and metastatic axillary lymph node tumors from 25 women with invasive breast cancer were amplified using 52 microsatellite markers defining 26 chromosomal regions commonly deleted in breast cancer. Levels and patterns of allelic imbalance (AI) within and between breast and lymph node tumors were assessed to identify chromosomal alterations unique to primary or metastatic tumors and to examine the timing of metastatic potential. The overall frequency of AI in primary breast tumors (0.24) was significantly greater (P < 0.001) than that in lymph node tumors (0.10), and congruent AI events were observed for <20% of informative markers. AI at chromosomes 11q23.3 and 17p13.3 occurred significantly more frequently (P < 0.05) in primary breast tumors alone; no chromosomal regions showed a significantly higher AI frequency in lymph nodes. Higher rates of AI in primary versus metastatic lymph node tumors suggest that acquisition of metastatic potential may be an early event in carcinogenesis, occurring before significant levels of AI accumulate in the primary tumor. In addition, patterns of AI were highly discordant between tumor types, suggesting that additional genetic alterations accumulated independently in the two cell populations.
Sensitivity to DNA Damage Is a Common Component of Hormone-Based Strategies for Protection of the Mammary Gland
Authors: Tu Yifan , Jerry D. Joseph , Pazik Brooke , Smith Schneider Sallie
Published: September 2005

An early full-term pregnancy significantly reduces the risk of getting breast cancer in women. In animals, this protection can be mimicked by a short-term exposure to physiologic doses of estrogen plus progesterone. Sensitization of p53 and up-regulation of transforming growth factor β are believed to be important aspects of the mechanism by which protection is imparted. Little is known, however, about the use of this pathway in response to other chemopreventive agents. In this article, we investigated the ability of retinoids, such as 9-cis retinoic acid, all-trans retinoic acid, and N-4-hydroxyphenylretinamide (4-HPR), to sensitize the ductal epithelial cells of virgin mammary glands to DNA damage responses. Using a whole-organ culture system, we observed enhanced cell death in response to γ-irradiation in the virgin tissues treated with retinoids for 72 hours. These retinoids were partially dependent on p53 and transforming growth factor β to exert their radiosensitizing effects. However, 4-HPR seemed to sensitize other cells or activate these pathways in a different manner as costimulation with ovarian hormones and 4-HPR was additive, whereas coculture of ovarian hormones and the natural retinoids did not increase amount of death. Taken together, these data suggest that sensitization of the mammary epithelium to p53-dependent apoptosis is a common pathway, which is engaged by retinoids as well as ovarian hormones.
Lipopolysaccharide Prevents Doxorubicin-Induced Apoptosis in RAW 264.7 Macrophage Cells by Inhibiting p53 Activation
Authors: Hassan Ferdaus , Islam Shamima , Mu Mya Mya , Ito Hiroyasu , Koide Naoki , Mori Isamu , Yoshida Tomoaki , Yokochi Takashi
Published: September 2005

The effect of lipopolysaccharide on doxorubicin-induced cell death was studied by using mouse RAW 264.7 macrophage cells. Pretreatment with lipopolysaccharide at 10 ng/mL prevented doxorubicin-induced cell death and the inhibition was roughly dependent on the concentration of lipopolysaccharide. Posttreatment with lipopolysaccharide for 1 hour also prevented doxorubicin-induced cell death. Lipopolysaccharide inhibited DNA fragmentation and caspase-3 activation in doxorubicin-treated RAW 264.7 cells, suggesting the prevention of doxorubicin-induced apoptosis. Lipopolysaccharide did not significantly inhibit doxorubicin-induced DNA damage detected by single-cell gel electrophoresis (comet) assay. Lipopolysaccharide definitely inhibited the stabilization and nuclear translocation of p53 in doxorubicin-treated RAW 264.7 cells. Lipopolysaccharide, as well as being an inhibitor of p53, abolished doxorubicin-induced apoptosis. Therefore, p53 was suggested to play a pivotal role in the prevention of doxorubicin-induced apoptosis in RAW 264.7 cells by lipopolysaccharide.
Who Comes First? The Role of the Prefrontal and Parietal Cortex in Cognitive Control
Authors: Brass Marcel , Ullsperger Markus , Knoesche Thomas R. , Cramon D. Yves von , Phillips Natalie A.
Published: September 2005

Cognitive control processes enable us to adjust our behavior to changing environmental demands. Although neuropsychological studies suggest that the critical cortical region for cognitive control is the prefrontal cortex, neuro-imaging studies have emphasized the interplay of prefrontal and parietal cortices. This raises the fundamental question about the different contributions of prefrontal and parietal areas in cognitive control. It was assumed that the prefrontal cortex biases processing in posterior brain regions. This assumption leads to the hypothesis that neural activity in the prefrontal cortex should precede parietal activity in cognitive control. The present study tested this assumption by combining results from functional magnetic resonance imaging (fMRI) providing high spatial resolution and event-related potentials (ERPs) to gain high temporal resolution. We collected ERP data using a modified task-switching paradigm. In this paradigm, a situation where the same task was indicated by two different cues was compared with a situation where two cues indicated different tasks. Only the latter condition required updating of the task set. Task-set updating was associated with a midline negative ERP deflection peaking around 470 msec. We placed dipoles in regions activated in a previous fMRI study that used the same paradigm (left inferior frontal junction, right inferior frontal gyrus, right parietal cortex) and fitted their directions and magnitudes to the ERP effect. The frontal dipoles contributed to the ERP effect earlier than the parietal dipole, providing support for the view that the prefrontal cortex is involved in updating of general task representations and biases relevant stimulus-response associations in the parietal cortex.
Rule-dependent Activity for Prosaccades and Antisaccades in the Primate Prefrontal Cortex
Authors: Everling Stefan , DeSouza Joseph F. X.
Published: September 2005

Everyday life typically requires behavior that involves far more than simple stimulus-response associations. Environmental cues are often ambiguous and require different actions depending on the situation. The prefrontal cortex (PFC) is thought to be crucial for this flexible control of behavior. An important task that probes this ability is the antisaccade task in which subjects have to suppress a glance towards a suddenly presented peripheral stimulus and instead look away from the stimulus to its mirror location. Here we recorded the activity of PFC neurons in monkeys trained to alternate between blocks of prosaccade and antisaccade trials with no external instruction cues. We found that the activity of many neurons was different between the two tasks during the fixation period before the peripheral stimulus was presented. These differences were already present on the first correct trials after a task switch. The activity of these neurons also discriminated between correct responses and errors. We hypothesize that the PFC provides bias signals to saccade-related areas that are necessary to preset the oculomotor system for different tasks.
Heightened cocaine-induced locomotor activity in adolescent compared to adult female rats
Authors: Catlow Briony J. , Kirstein Cheryl L.
Published: September 2005

Initiation and experimentation with illicit drugs often occurs in adolescence. Evidence suggests that adolescent rats are more sensitive to some of the effects of drugs of abuse than adult rats. The present study investigated whether adolescent and adult female Sprague Dawley rats differ in cocaine-induced locomotor activity. Animals were placed in the test environment for 30 minutes, and then administered an intraperitoneal (IP) injection of either cocaine (20mg/kg) or saline (0.9%). Both adult and adolescent animals showed significant increases in locomotor activity as a result of cocaine administration compared to saline controls. Interestingly, cocaine induced significantly more locomotor activity in the adolescent females compared to the adults, demonstrating that cocaine acts differently in developing animals.
A long-term study of the effects of diazinon on sleep, the electrocorticogram and cognitive behaviour in common marmosets
Authors: Muggleton N. G. , Smith A. J. , Scott E. A. M. , Wilson S. J. , Pearce P. C.
Published: September 2005

The long-term sequelae of exposure to low doses of organophosphate compounds are ill defined, with effects variously reported on a range of indices of central nervous system functions such as sleep, cognitive performance and electroencephalogram (EEG). These indices were examined in common marmosets exposed to a range of doses of the organophosphorous sheep dip, diazinon. Cognitive performance was assessed by means of elements from the Cambridge Neuropsychological Test Automated Battery (CANTAB), and radiotelemetry techniques were employed to monitor the electrocorticogram and sleep patterns. Data were collected for 12 months following intramuscular administration of a single dose of diazinon (10, 90 or 130mg.kg 1) or vehicle. Although high levels of erythrocyte acetylcholinesterase (AChE) inhibition (up to 82%) and short-term changes in sleep patterns were seen, there was no evidence of biologically significant long-term changes in any measures. The effects of multiple exposures, impurities or mixtures of OP compounds remain to be investigated.
Neonatal symptoms following maternal paroxetine treatment: Serotonin toxicity or paroxetine discontinuation syndrome?
Authors: Haddad P. M. , Pal B. R. , Clarke P. , Wieck A. , Sridhiran S.
Published: September 2005

We report a case of neonatal symptoms of irritability, increased tonus and convulsions after in-utero exposure to paroxetine 30mg/day. The infant’s symptoms commenced on the first day after birth and persisted for 10 days. Paroxetine levels were undetectable on day 6. Extensive investigations excluded infective and metabolic causes. Serotonin toxicity due to paroxetine seems the most likely mechanism, though an important differential diagnosis is a paroxetine discontinuation (withdrawal) syndrome. Differentiating between these two syndromes in the neonate presents a dilemma for clinicians. Irrespective of the mechanism, we recommend that all neonates exposed to antidepressants, particularly serotonin reuptake inhibitors (SSRIs), during the last trimester should be followed-up closely for adverse symptoms commencing in the first 10 days after birth. The possibility of such symptoms needs to be discussed with women who are considering starting or continuing antidepressant treatment in pregnancy. All neonatal adverse drug events should be reported to a pharmacovigilance centre. Further research is warranted.
Capabilities, resources, and systematic injustice: a case of gender inequality
Authors: Browne Jude , Stears Marc
Published: September 2005

Focusing on the debate between resource egalitarians and capability theorists, with particular attention to gender equality, this article rejects the prevailing assumption that the ‘capability approach’ to equality, as outlined by Amartya Sen, is better able to respond to important empirically identifiable inequalities than its resource egalitarian alternative, as developed by Ronald Dworkin. Developing and expanding upon the often overlooked Dworkinian ‘principle of independence’, the article contends that resource egalitarianism is capable of identifying and responding to a complex set of structural inequalities that remain outside the purview of the capability approach.
Does National Culture Affect Willingness to Justify Ethically Suspect Behaviors?
Authors: Parboteeah K. Praveen , Bronson James W. , Cullen John B.
Published: September 2005

In this article, we examine the relationship of the Global Leadership and Organizational Behavior Effectiveness national culture dimensions with the willingness of 27,459 individuals located in 21 nations to justify ethically suspect behaviors. Hierarchical Linear Modeling (HLM), a technique well suited for cross-level studies, is employed to test the hypothesized relationships from data made available by the World Values Survey. Results support our hypotheses with regard to performance orientation, assertiveness, institutional collectivism and humane orientation. However, results surprisingly reject our hypotheses on power distance and uncertainty avoidance. We discuss these counterintuitive findings and elaborate on the study’s implications for both research and practice.
Cultural Diversity and Its Impact on Social Interactive Processes
Authors: Vallaster Christine
Published: September 2005

In this article we report findings from three longitudinal studies carried out to understand the social interactive processes in multicultural groups observed in their organizational settings. Its aim was to explore the dynamics of cognitive, affective and communicative aspects during the development of a shared understanding. In particular, crystallizing the effect of culture in a temporal setting was considered. Data give reason to believe that country-of-origin diversity aspects during this process depend on whether employees feel this is salient in a particular context. The findings are of particular value to intercultural managers in their role as project leaders. For successful cooperation among culturally diverse group members, they need to facilitate social interactive processes by balancing perceived differences.
Comparing the Validity of Turnover Predictors in the United States and Mexico
Authors: Posthuma Richard A. , Joplin Janice R.W. , Maertz Carl P.
Published: September 2005

This article compared the relative validity of traditional predictors of turnover intentions using samples from the USA and Mexico. Matched samples of retail grocery store employees (USA: N = 187; Mexico: N = 150) completed questionnaires that reported perceptions of inter-role conflict, positive affect, job satisfaction, perceived ease of movement and turnover intentions. Results indicate that job satisfaction and perceived ease of movement predicted turnover intentions in both the USA and Mexico. However, job satisfaction and perceived ease of movement were stronger predictors of turnover intentions in the USA. Unexpectedly, work-family and work-personal conflict did not predict turnover intentions in either sample.
Management of Private-aided Higher Education in Karnataka, India
Authors: Tooley James
Published: September 2005

The Grant-in-Aid (GIA) higher education sector in Karnataka, India, is examined as an example of a well-established public-private partnership (PPP). Interviews with senior officials in the Government of Karnataka, and in two contrasting Regions, centred around Gulbarga and Mysore, together with visits to GIA and private-unaided (PUA) colleges were undertaken. The study showed how devolved financial management led to problems of potential misuse of subsidy and to substantial inefficiencies. The regulation of the sector is explored, revealing inconsistencies between theory and practice, and unforeseen consequences in terms of a lack of teacher accountability and low investment. Considerations concerning equity are outlined, noting how GIA proponents who argued that it was effective in helping the poor might not be on strong grounds. Finally, implications are discussed for PPPs more generally.
Secondary Teacher Workload and Job Satisfaction
Authors: Butt Graham , Lance Ann
Published: September 2005

This article analyses the views of secondary school teachers involved in the Transforming the School Workforce: Pathfinder Project—a project designed to address issues of teacher workload and job satisfaction. The initiative was launched in 2002 by the Department for Education and Skills (DfES) to enable 32 pilot schools to explore ways in which they might restructure their working practices and reduce teacher workload. Funding was provided for schools to benefit from consultancy support, the training of headteachers, the employment of additional teaching assistants, the provision of ICT hardware and software, the training of bursars/school managers and for capital build projects. Here we concentrate on the evaluation of the Pathfinder Project with particular reference to possible changes in workload and job satisfaction of secondary teachers in the 12 secondary schools involved in the project. The reported weekly and holiday hours worked by secondary teachers are analysed across the duration of the project, as are patterns of evening and weekend work. Teachers’ views on job satisfaction are also analysed in conjunction with their perspectives on workload, culminating in a discussion of their solutions to the problems of excessive workload. The relationship between teacher workload, job satisfaction and work-life balance is explored within the context of the future modernization of the entire school workforce.
Departmental Leadership and Management in Chartered and Statutory Universities
Authors: Smith Robert
Published: September 2005

This article presents the findings of two case studies of leadership and management in engineering departments in two British universities, one a chartered university and one a statutory university. The studies are the first in a series of ‘pairs’ of such studies in departments of various academic discipline and size, in the two types of university. Data were collected by semi-structured interviews with the heads of the two departments and members of their staff who have leadership and/or management roles. The most striking feature of the study is the very different cultures and organizational structures of the two departments and their very different approaches to leadership and management. The studies also raises questions regarding the findings of other researches and writings, namely that heads of department have unreasonably high workloads, that large university departments are difficult to manage and that collegiality is the preferred model of decision-making
Immune sensitization of equine bronchus: glutathione, IL-1β expression and tissue responsiveness
Authors: Matera MG , Calzetta L , Peli A , Scagliarini A , Matera C , Cazzola M
Published: September 2005

Background

Increasing clinical epidemiological and experimental evidence indicates that excess of production of reactive oxygen free radicals (ROS) induced by an oxidative stress is involved in the pathogenesis of a number of human airway disorders, as well as equine recurrent airway obstruction. Free-radicals modulate the activation of transcription factors, such as nuclear factor-(NF)-κB and activator protein (AP)-1, in several different cells. This activation leads to expression of many pro-inflammatory cytokines, including interleukin (IL)-1β. We have hypothesized that equine airway sensitization might induce an oxidative stress and increase the ROS production, which in turn might enhance a production of IL-1β and airway hyperresponsiveness.

Methods

We have examined the effect of passive sensitization on IL-1β mRNA expression and electrical field stimulation (EFS)-induced contraction in equine isolated bronchi, and the potential interference of reduced-glutathione (GSH), an antioxidant, with these responses. Bronchi passively sensitized with serum from animals suffering from heaves and having high total level of IgE, and control tissues, either pretreated or not with GSH (100 μM), were used to quantify IL-1β mRNA. Other tissues were used to study the effect of EFS (3–10–25 Hz).

Results

Mean IL-1β mRNA expression was higher in passively sensitized than in control rings. GSH significantly (p< 0.05) reduced the IL-1β mRNA expression only in passively sensitized bronchi. ELF induced a frequency-dependent contraction in both non-sensitized and passively sensitized tissues, with a significantly greater response always observed in sensitized tissues. GSH did not modify the EFS-induced contraction in non-sensitized bronchi, but significantly (p< 0.05) decreased it in passively sensitized tissues.

Conclusion

Our data indicate that the passive sensitization of equine bronchi induces inflammation and hyperresponsiveness. These effects might be due to an oxidative stress because a pretreatment with GSH decreased the increased IL-1β mRNA expression and responsiveness to EFS of passively sensitized bronchi.
Comparative perspectives towards communicative activities among elementary school teachers in South Korea, Japan and Taiwan
Authors: Butler Yuko Goto
Published: September 2005

With the spread of globalization and information technology, the goal of English education in East Asian countries has recently undergone drastic change, with one such change being the introduction of English at the elementary school level. Based on a sociocultural theoretical framework, this study attempts to identify and compare the ways in which local elementary school teachers consider classroom activities in English that are ‘effective’ in their given sociocultural and policy contexts. Employing multivocal ethnography, classroom activities in these countries were videotaped and edited. The edited videotape was shown to elementary school teachers in South Korea, Japan and Taiwan, who were then asked to discuss various aspects of teaching practice and activities in small groups. Among the many issues raised by teachers, this paper focuses on their concerns and challenges in employing communicative activities with respect to (1) creating motives and goals that drive communicative activities; (2) identifying developmentally appropriate mediational means; and (3) situating activities in specific contexts. The study found that teachers’ challenges were due to a lack of understanding of three factors, including what constitutes ‘teaching for communicative purposes’, the roles that developmental factors play in EFL learning and teaching, and strategies for harmonizing learning/teaching and context.
The Heats of Chemical Reactions: the Van't-Hoff Equation and Calorimetry
Authors: Stepanov I. A.
Published: September 2005

It is shown that the difference between the heat of chemical reaction derived by the Van't-Hoff equation, ΔH
0, and measured by calorimetry, ΔQ
0, is PΔV
0.
Averaged Trajectory of Random Walk Fluctuations Having a Fixed Lifetime and its Application in Characterization of Simplest Chemical Equilibrium
Authors: Šolc M.
Published: September 2005

Recently, we found that for a simple first-order reaction having equilibrium constant equal to 1, the amplitudes of equilibrium fluctuations can be, on the discrete time scale (scale of reaction events), satisfactorily described using the random walk approximation for the distribution and mean amplitude of fluctuation having the fixed lifetime 2r reaction events. Below, we propose another characterization of fluctuations in the random walk introducing an averaged trajectory of fluctuations and suggest another formula for the mean amplitude of fluctuations having a fixed length. The results are used in characterization of equilibrium fluctuations of first order reversible chemical reaction having the equilibrium constant equal to 1.
Device Physics of Solution‐Processed Organic Field‐Effect Transistors
Authors: Sirringhaus H.
Published: September 2005

Field‐effect transistors based on solution‐processible organic semiconductors have experienced impressive improvements in both performance and reliability in recent years, and printing‐based manufacturing processes for integrated transistor circuits are being developed to realize low‐cost, large‐area electronic products on flexible substrates. This article reviews the materials, charge‐transport, and device physics of solution‐processed organic field‐effect transistors, focusing in particular on the physics of the active semiconductor/dielectric interface. Issues such as the relationship between microstructure and charge transport, the critical role of the gate dielectric, the influence of polaronic relaxation and disorder effects on charge transport, charge‐injection mechanisms, and the current understanding of mechanisms for charge trapping are reviewed. Many interesting questions on how the molecular and electronic structures and the presence of defects at organic/organic heterointerfaces influence the device performance and stability remain to be explored.
Substoichiometric conversion of biomass and solid wastes to energy in packed beds
Authors: Yang Yao Bin , Sharifi Vida Nasserzadeh , Swithenbank Jim
Published: September 2005

Biomass and municipal solid wastes are two of the sustainable energy resources. Countercurrent, substoichiometric conversion of these fuels into energy in packed beds has the benefits of lower tar and dust carryover in flue gases, and therefore gas‐treatment procedures can be simplified and the running cost is reduced. In this paper, mathematical simulation is performed on a large‐scale plant furnace for both municipal solid wastes and biomass fuels in a range of operating conditions. The temperature profile inside the moving packed bed of the same system was measured by an in situ electronic device for the baseline case to partially validate the simulation results. Mathematical simulation indicates that by using variable grate speed to obtain constant bed height, a typical moving‐bed furnace can achieve over 99% of conversion efficiency with only 40–50% of the normal primary air supply, without loss in throughput; the char conversion rate is significantly lower than the devolatilization rate in the bed and the char conversion process occupies over half of the total bed length, whereas fuel devolatilization occupies only one‐third or more of the bed length. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Formability and accuracy of micropolymer compound with added nanomaterials in microinjection molding
Authors: Huang C. K. , Chiu S. W.
Published: September 2005

The miniaturization of components has been progressing rapidly because of developments in microelectronics, optoelectronics, and biotechnology. Recently, the use of plastic materials with added fillers has become a potential alternative because of their versatility and ease of batch fabrication. This article investigates the formability and accuracy of the polymer with added nanopowders (10–30 nm diameter) during microinjection molding. One mold with four cavities is used to illustrate the filling behavior and accuracy of the microparts. The integrated circuit microfeature illustrates the formability of the polymer with added nanopowders. Experiments show that the shrinkage is significantly reduced when the nanopowder content is increased. The polymer with 30% ZnO nanopowder content shows 58.3% less shrinkage compared to pure polypropylene. One mold with four parts and the microfeature are successfully manufactured using a custom‐made microinjection machine when nanopowders are added to the polymer. However, the microfeature with added fillers, which had a diameter of 10 μm and a length of 10–30 μm, cannot be duplicated through microinjection molding. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1865–1874, 2005
Copolymers of 2‐hydroxyethylmethacrylate and N‐maleoylglycine: Synthesis, characterization, and swelling behavior
Authors: Jeria Manuel , Pizarro Guadalupe del C. , Marambio Oscar G. , Huerta Margarita , Valencia Paulina , Rivas Bernabé L.
Published: September 2005

We synthesized copolymers based on 2‐hydroxyethylmethacrylate and N‐maleoylglycine by varying the monomer feed composition. The copolymers were characterized by Fourier transform infrared spectroscopy, elemental analysis, and thermogravimetry/differential scanning calorimetry as the thermal analysis method. The thermograms showed that the polymers degraded in a single‐stage process. For the hydrogels of poly(2‐hydroxyethylmethacrylate) and poly(2‐hydroxyethylmethacrylate‐co‐N‐maleoylglycine) [poly(HEMA‐co‐MG)], swelling behaviors were investigated by the immersion of the gels in solution at pH's of 3, 5, and 7. The swelling studies were performed with and without ionic strength. The copolymer composition had a significant effect on the equilibrium swelling behavior of poly(HEMA‐co‐MG). With those soluble copolymer fractions, we obtained a low conversion (<30%); the monomer reactivity ratios were estimated by the Kelen–Tüdös linear method. The data indicated that poly(HEMA‐co‐MG) was a random copolymer. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1897–1902, 2005