bluuebunny/crossref_metadata_2025 huggingface dataset:
But let us not forget John Collier
Authors: Neilsen Eric H.
Published: December 2006

We propose that John Collier was integrally involved in the development of action research and deserves to be recognized as a cofounder of the field. We offer a brief biography of Collier, review the roots of his approach to action research, and then compare Lewin’s principles of action research as articulated by Bargal with excerpts from an article Collier wrote in 1945, a year before Lewin’s first writing on the subject. We conclude with a discussion of why Lewin did not give Collier more credit, even though the two were close friends. We hypothesize that Lewin’s version of action research was more science oriented, while Collier’s was more exclusively focused on democratic collaboration in the treatment of important social issues.
Participatory action research
Authors: Burgess Judy
Published: December 2006

This article examines the tensions and challenges of a graduate student maneuvering the institutional hierarchies in her journey of participatory action research (PAR). By using a first-person action research framework, the researcher moves back and forth exploring the prose of others, and revealing her reflexive self-inquiry of underlying assumptions and beliefs. Iterations of insider-outsider positionality, drawing on and integrating paradigms, reconciling multiple roles and perspectives, exploring the complexity of power relations, and uncovering the promises and perils of PAR, moves the researcher toward a partnership with her community of inquiry. First-person action research unfolds a process of self-transformation.
Action research literature 2004-2006
Authors: Dick Bob
Published: December 2006

This review of recent action research books covers the period from about mid-2004 to mid-2006, complementing an earlier review (Dick, 2004). After noting some important recent additions to the action research literature, I address the literature on several different applications of action research including education, community, participatory development, and organizations. There are briefer sections on other topics. Action research journals and special issues of other journals are also identified. Finally, I identify some themes and trends in the action research literature.
Effect of ageing on the nature and interlayering of mixed hydroxy A1-Fe-montmorillonite complexes
Authors: Colombo C. , Violante A.
Published: December 2006

Mixed hydroxy Al-Fe-montmorillonite complexes (5 mmol of Al+Fe per g of clay) were prepared at pH 5.0 by mixing different amounts of Al(NO3)3 and Fe(NO3)3 to give initial Fe/Al molar ratios (R) of 0, 0.1, 0.25, 0.5, 1.0, 4.0, 10.0 or ∞. The effect of ageing on the interlayering, mineralogy, chemical composition, CEC and external surface area of the complexes was studied. The degree of interlayering of freshly prepared and aged complexes (up to 120 days at 50°C) was always greater in the samples with R ranging from 0.5 to 4. Gibbsite and hematite (with traces of goethite) formed in the samples with R ⩽ 1 and R∞, respectively. No crystalline Fe oxide was detected by XRD analyses in the complexes with R ranging from 0.1 to 10, whereas no crystalline Al and Fe oxides were formed in the complexes at R = 4–10. However, some evidence suggests the possible formation of a microcrystalline Fe oxide/oxyhydroxide undetectable by XRD analyses in the complexes richer in Fe. The CEC and the surface area of the freshly prepared mixed hydroxy Al-Fe-montmorillonite complexes increased with increasing R. Large quantities of Al+Fe were solubilized by oxalate in the complexes with R ⩾ 0.5, even after ageing for 120 days at 50°C, indicating that interlayering of Al-Fe species at certain Fe/Al molar ratios was particularly stable.
X-ray diffraction, infrared and TGA/DTG analysis of hydrated nacrite
Authors: Ben Haj Amara A.
Published: December 2006

An homogenous 8.4 Å hydrate was obtained after washing intercalated KAc- nacrite. X-ray diffraction analysis based on comparison of the experimental and calculated profiles enabled the amount of water (one molecule per Si2Al2O5(OH)4) and the z coordinate along c* (6.5 Å) to be determined. The hydration state was accompanied by a decrease in the coherent domain along c* in the order nacrite > KAc-nacrite > H2O-nacrite. The IR spectrum of the hydrated nacrite showed an evolution of the structure with a shift of ν(OH) from 3702, 3649 and 3630 cm−1 to 3690, 3641 and 3620 cm−1, respectively for the nacrite hydroxyls. The ν(OH) stretching bands of the interlayer water appeared at 3602 and 3545 cm−1 and their bending band at 1655 cm−1. The TGA/DTG analysis of the air-dry hydrated nacrite showed a loss of water at 245°C the weight loss (1 molecule per Si2Al2O5(OH)4) corresponding to the interlamellar water, in agreement with that determined by XRD.
Kaolinite hydroxyls – a Raman microscopy study
Authors: Frost R. L. , van der Gaast S. J.
Published: December 2006

Raman microscopy of the kaolinite polymorphs was used to study single crystals and bundles of aligned crystals of kaolinite. The spectra of the hydroxyl stretching region were both sample and orientation dependent. Kaolinites can be classified into two groups according to the ratio of the intensities of the 3685 and 3695 cm−1 bands. No relationship was found between the d-spacing and the crystal domain size measurement from the 001 reflection and the Raman spectral intensities indicating the Raman spectra are independent of d-spacing and crystallinity. However, a relationship of the crystallinity in the a-b direction and intensities of the 3685 and 3695 cm−1 bands indicate that the relative position of one layer to the other determines the position of the inner surface hydroxyl groups and the hydrogen bonding with the oxygen of the opposite layer. A new hypothesis based on symmetric and non-symmetric hydrogen bonding of the inner surface hydroxyl groups is proposed to explain the two inner surface hydroxyl bands centred at 3685 and 3695 cm−1. The bands at 3670 and 3650 cm−1 are described in terms of the out-of-phase vibrations of the in-phase vibrations at 3695 and 3685 cm−1.
Dehydration and rehydration of vermiculites: III. Phlogopitic Sr- and Ba-vermiculite
Authors: Graf v. Reichenbach H. , Beyer J.
Published: December 2006

Dehydration and rehydration of a phlogopitic vermiculite saturated with either Sr2+ or Ba2+ were studied by thermoanalysis (TG, DSC, DTA) and by in situ X-ray powder diffractometry. A detailed analysis of the relationship between temperature and state of hydration of the vermiculites close to equilibrium at atmospheric pressure was rendered possible by use of low heating rates in combination with a fast recording position-sensitive detector. For Sr-vermiculite, the results reveal the existence of a number of distinct states of hydration characterized by basal spacings of 1.54, 1.51, 1.49, 1.23, 1.21 and 0.96 nm. The Ba-vermiculite failed to develop a two-layer hydrate even in contact with water. Its one-layer hydrate (1.24 nm) was reversibly transformed into an incompletely dehydrated ordered ‘mica-structure’ (1.00-0.99 urn), before an irreversibly dehydrated structure was attained at temperatures exceeding 700°C The formation of regular 1:1 interstratification was confirmed for all transformations characterized by a change in the number of water layers. The concluding compilation summarizes basal spacings, stacking orders, layer translations and specific water contents for all discrete states of hydration observed in our experiments at saturation of vermiculite with different alkaline earth cations.
The structure of an intercalated ordered kaolinite — a Raman microscopy study
Authors: Frost R. L. , Tran T. H. , Kristof J.
Published: December 2006

Changes in the molecular structure of a highly ordered kaolinite, intercalated with urea and potassium acetate, have been studied using Raman microscopy. A new Raman band, attributed to the inner surface hydroxyl groups strongly hydrogen bound to the acetate, is observed at 3605 cm-1 for the potassium acetate intercalate with the consequential loss of intensity in the bands at 3652, 3670, 3684 and 3693 cm-1. Remarkable changes in intensity of the Raman spectral bands of the low-frequency region of the kaolinite occurred upon intercalation. In particular, the 144 and 935 cm-1 bands increased by an order of magnitude and were found to be polarized. These spectroscopic changes provide evidence for the inner surface hydroxyl group-acetate bond being at an angle approaching 90° to the 001 face. Decreases in intensity of the bands at 243, 271 and 336 cm-1 were observed. The urea intercalate shows additional Raman bands at 3387, 3408 and 3500 cm-1 which are attributed to N-H vibrations after formation of the urea-kaolinite complex. Changes in the spectra of the inserting molecules were also observed.
Characterization and catalytic properties of a saponite clay modified by acid activation
Authors: Kooli F. , Jones W.
Published: December 2006

A natural saponite was acid activated at room temperature or 90°C with different acid/clay ratios and the products were characterized by powder X-ray diffraction, infrared spectroscopy and thermogravimetry. The leaching of Mg from the octahedral sheets is enhanced by an increase in the acid/clay ratio and by an increase in temperature of activation. Textural properties are reported, and it appears that they are strongly correlated to the presence of a noncrystalline silica phase which is formed during the acid activation process. The desorption of cyclohexylamine indicates that for samples activated at 90°C the number of acid sites in the acidactivated saponites decreases following severe acid treatment. Infrared spectroscopy of adsorbed pyridine on samples after calcination at 500°C suggests that acid activation at 90°C produces a single type of Bronsted site but two types of Lewis sites whereas activation at room temperature results in only one type of Lewis site in addition to a Brønsted site. The two Lewis sites are suggested to originate from residual Al in the clay structure and to AI exsolved from the layers during activation. The dehydration of pentan-1-ol has been used as a further probe to measure acidity by monitoring the degree of conversion and selectivity for the different samples.
Bmi-1 is induced by the Epstein-Barr virus oncogene LMP1 and regulates the expression of viral target genes in Hodgkin lymphoma cells
Authors: Dutton Amanda , Woodman Ciaran B. , Chukwuma Marilyn B. , Last James I. K. , Wei Wenbin , Vockerodt Martina , Baumforth Karl R. N. , Flavell Joanne R. , Rowe Martin , Taylor A. Malcolm R. , Young Lawrence S. , Murray Paul G.
Published: December 2006

Polycomb group (PcG) proteins are chromatin modifiers that are necessary for the maintenance and renewal of embryonic and adult stem cells. However, overexpression of the PcG protein, Bmi-1, causes lymphoma in transgenic mice. We show that Bmi-1 is up-regulated in Hodgkin lymphoma (HL) cells by the Epstein-Barr virus (EBV) oncogene latent membrane protein-1 (LMP1) and that this up-regulation is mediated by NF-κB signaling. We also show that Bmi-1 is up-regulated by NF-κB in EBV-negative HL cells. Down-regulation of LMP1 and Bmi-1 decreased the survival of HL cells, suggesting that Bmi-1 may mediate the prosurvival effects of LMP1-induced NF-κB signaling in HL cells. Transcriptional targets of Bmi-1 were identified after its knockdown in an HL cell line. We show here that Bmi-1 and LMP1 down-regulate the ataxia telangiectasia–mutated (ATM) tumor suppressor and conclude that Bmi-1 contributes to LMP1-induced oncogenesis in HL.
CpG oligodeoxynucleotides allow for effective adoptive T-cell therapy in chronic retroviral infection
Authors: Kraft Anke R. M. , Krux Frank , Schimmer Simone , Ohlen Claes , Greenberg Philip D. , Dittmer Ulf
Published: December 2006

Adoptive T-cell therapy in cancer or chronic viral infections is often impeded by the development of functional impairment of the transferred cells. To overcome this therapeutic limitation we combined adoptive transfer of naive, virus-specific CD8+ T cells with immunostimulative CpG oligodeoxynucleotides (ODNs) in mice chronically infected with the Friend retrovirus. The CpG-ODN co-injection prevented the T cells from developing functional defects in IFNγ and granzyme production and degranulation of cytotoxic molecules. Thus, the transferred T cells were able to reduce chronic viral loads when combined with CpG-ODNs. This strategy provides a new approach for developing successful adoptive T-cell therapy against chronic infections.
Cartography of gene expression in CD8 single cells: novel CCR7− subsets suggest differentiation independent of CD45RA expression
Authors: Monteiro Marta , Evaristo César , Legrand Agnès , Nicoletti Antonino , Rocha Benedita
Published: December 2006

Understanding the distribution, function, and lineage relationship of CD8+ T-cell subpopulations is of fundamental value for the monitoring of the immune system in several experimental and clinical situations. However, the available data concerning the description of effector and memory CD8+ subsets in humans remain rather fragmentary because different studies favored the usage of distinct and restricted sets of cell surface markers and functional parameters. We associated multiple markers to subdivide CD8+ T cells into 14 different cell types, several of which were not described previously, and evaluated the coexpression of 18 genes simultaneously in individual cells from each subset. Our results show that each subset has a defined pattern of gene expression. Moreover, effector gene expression of CCR7− cells correlated only with CD27 expression levels and CD27/CD28 coexpression but not with CD45RA/R0 phenotypes. Our findings thus describe new CD8+ cell subsets, allow the identification of relatively homogeneous CD8+ subpopulations, provide a predictable and precise correlation between particular cell surface markers and CD8+ T-cell functional properties, and identify effector cells present in both CCR7−CD45RA+ and CCR7−CD45R0+ compartments. The results also indicate that activated cells might modulate the expression of CD45RA/R0 asynchronously rather than CCR7−CD45RA+ cells always issuing from CD45RA− precursors.
Interleukin 2 gene transcription is regulated by Ikaros-induced changes in histone acetylation in anergic T cells
Authors: Bandyopadhyay Sanmay , Duré Myrianne , Paroder Monika , Soto-Nieves Noemí , Puga Irene , Macián Fernando
Published: December 2006

In T cells anergy may be evoked by an unbalanced stimulation of the T-cell receptor in the absence of costimulation. Anergic T cells are unresponsive to new antigen receptor engagement and do not produce interleukin 2. We present evidence that anergizing stimuli induce changes in histone acetylation, which mediates transcriptional repression of interleukin 2 expression. In response to calcium signaling, anergic T cells up-regulate the expression of Ikaros, a zinc finger transcription factor essential for lymphoid lineage determination. Ikaros binds to the interleukin 2 promoter where it induces histone deacetylation. Confirming the role of Ikaros in the induction of T-cell anergy, cells with reduced Ikaros activity show defective inactivation in response to an anergizing stimulus. We propose a model in which tolerizing stimuli induce epigenetic changes on the interleukin 2 locus that are responsible for the stable inhibition of the expression of this cytokine in anergic T cells.
Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma
Authors: Palumbo Antonio , Ambrosini Maria Teresa , Benevolo Giulia , Pregno Patrizia , Pescosta Norbert , Callea Vincenzo , Cangialosi Clotilde , Caravita Tommaso , Morabito Fortunato , Musto Pellegrino , Bringhen Sara , Falco Patrizia , Avonto Ilaria , Cavallo Federica , Boccadoro Mario ,   for the Italian Multiple Myeloma Network, Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA)
Published: December 2006

In multiple myeloma (MM), the addition of thalidomide or bortezomib to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter phase 1/2 trial, dosing, safety, and efficacy of the 4-drug combination, bortezomib, melphalan, prednisone, and thalidomide (VMPT) was determined. Bortezomib was administered at 3 dose levels (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2) on days 1, 4, 15, and 22; melphalan was given at a dose of 6 mg/m2 on days 1 through 5 and prednisone at 60 mg/m2 on days 1 through 5. Thalidomide was delivered at 50 mg on days 1 through 35. Each course was repeated every 35 days. The maximum tolerated dose of bortezomib was 1.3 mg/m2. Thirty patients with relapsed or refractory MM were enrolled; 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good PR. Among 14 patients who received VMPT as second-line treatment, the PR rate was 79% and the immunofixation-negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 nonhematologic adverse events included infections (5 patients), fatigue (1), vasculitis (1), and peripheral neuropathy (2); no grade 4 toxicities were recorded. Initial results showed that VMPT is an effective salvage therapy with a very high proportion of responses. The incidence of neurotoxicities was unexpectedly low.
Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia
Authors: Scheinberg Phillip , Fischer Steven H. , Li Li , Nunez Olga , Wu Colin O. , Sloand Elaine M. , Cohen Jeffrey I. , Young Neal S. , John Barrett A.
Published: December 2006

The natural history of EBV and CMV reactivation and the potential for serious complications following antibody-based immunosuppressive treatment for bone marrow failure syndromes in the absence of transplantation is not known. We monitored blood for EBV and CMV reactivation by polymerase chain reaction (PCR) weekly in 78 consecutive patients (total of 99 immunosuppressive courses) with aplastic anemia. Four regimens were studied: (1) HC, horse ATG/cyclosporine; (2) HCS, horse ATG/CsA/sirolimus; (3) RC, rabbit ATG/CsA; and (4) CP, alemtuzumab. There were no cases of EBV or CMV disease, but EBV reactivation occurred in 82 (87%) of 94 and CMV reactivation in 19 (33%) of 57 seropositive patients after starting immunosuppression. The median peak EBV copies were higher in the RC group when compared with HC, HCS, and alemtuzumab (P < .001). The median duration of PCR positivity for EBV was higher in the RC group compared with HC, HCS, and alemtuzumab (P = .001). Subclinical reactivation of both EBV and CMV is common and nearly always self-limited in patients with bone marrow failure receiving immunosuppression; different regimens are associated with different intensity of immunosuppression as measured by viral load and lymphocyte count; and viral reactivation patterns differ according to immunosuppressive regimens.
Epigenetic regulation of Wnt-signaling pathway in acute lymphoblastic leukemia
Authors: Román-Gómez José , Cordeu Lucia , Agirre Xabier , Jiménez-Velasco Antonio , San José-Eneriz Edurne , Garate Leire , Calasanz María José , Heiniger Anabel , Torres Antonio , Prosper Felipe
Published: December 2006

Activation of the Wnt/β-catenin signaling pathway is a hallmark of a number of solid tumors. We analyzed the regulation of the Wnt/β-catenin pathway in acute lymphoblastic leukemia (ALL) and its role in the pathogenesis of the disease. We found that expression of the Wnt inhibitors sFRP1, sFRP2, sFRP4, sFRP5, WIF1, Dkk3, and Hdpr1 was down-regulated due to abnormal promoter methylation in ALL cell lines and samples from patients with ALL. Methylation of Wnt inhibitors was associated with activation of the Wnt-signaling pathway as demonstrated by the up-regulation of the Wnt target genes WNT16, FZ3, TCF1, LEF1, and cyclin D1 in cell lines and samples and the nuclear localization of β-catenin in cell lines. Treatment of ALL cells with the Wnt inhibitor quercetin or with the demethylating agent 5-aza-2′-deoxycytidine induced an inactivation of the Wnt pathway and induced apoptosis of ALL cells. Finally, in a group of 261 patients with newly diagnosed ALL, abnormal methylation of Wnt inhibitors was associated with decreased 10-year disease-free survival (25% versus 66% respectively, P < .001) and overall survival (28% versus 61% respectively, P = .001). Our results indicate a role of abnormal Wnt signaling in ALL and establish a group of patients with a significantly worse prognosis (methylated group).
Cohort effects in dynamic models and their impact on vaccination programmes: an example from Hepatitis A
Authors: Srinivasa Rao Arni SR , Chen Maggie H , Pham Ba' Z , Tricco Andrea C , Gilca Vladimir , Duval Bernard , Krahn Murray D , Bauch Chris T
Published: December 2006

Background

Infection rates for many infectious diseases have declined over the past century. This has created a cohort effect, whereby older individuals experienced a higher infection rate in their past than younger individuals do now. As a result, age-stratified seroprevalence profiles often differ from what would be expected from constant infection rates.

Methods

Here, we account for the cohort effect by fitting an age-structured compartmental model with declining transmission rates to Hepatitis A seroprevalence data for Canadian-born individuals. We compare the predicted impact of universal vaccination with and without including the cohort effect in the dynamic model.

Results

We find that Hepatitis A transmissibility has declined by a factor of 2.8 since the early twentieth century. When the cohort effect is not included in the model, incidence and mortality both with and without vaccination are significantly over-predicted. Incidence (respectively mortality) over a 20 year period of universal vaccination is 34% (respectively 90%) higher than if the cohort effect is included. The percentage reduction in incidence and mortality due to vaccination are also over-predicted when the cohort effect is not included. Similar effects are likely for many other infectious diseases where infection rates have declined significantly over past decades and where immunity is lifelong.

Conclusion

Failure to account for cohort effects has implications for interpreting seroprevalence data and predicting the impact of vaccination programmes with dynamic models. Cohort effects should be included in dynamic modelling studies whenever applicable.
Heterogeneity of mammary lesions represent molecular differences
Authors: Namba Ruria , Maglione Jeannie E , Davis Ryan R , Baron Colin A , Liu Stephenie , Carmack Condie E , Young Lawrence JT , Borowsky Alexander D , Cardiff Robert D , Gregg Jeffrey P
Published: December 2006

Background

Human breast cancer is a heterogeneous disease, histopathologically, molecularly and phenotypically. The molecular basis of this heterogeneity is not well understood. We have used a mouse model of DCIS that consists of unique lines of mammary intraepithelial neoplasia (MIN) outgrowths, the premalignant lesion in the mouse that progress to invasive carcinoma, to understand the molecular changes that are characteristic to certain phenotypes. Each MIN-O line has distinguishable morphologies, metastatic potentials and estrogen dependencies.

Methods

We utilized oligonucleotide expression arrays and high resolution array comparative genomic hybridization (aCGH) to investigate whole genome expression patterns and whole genome aberrations in both the MIN-O and tumor from four different MIN-O lines that each have different phenotypes. From the whole genome analysis at 35 kb resolution, we found that chromosome 1, 2, 10, and 11 were frequently associated with whole chromosome gains in the MIN-Os. In particular, two MIN-O lines had the majority of the chromosome gains. Although we did not find any whole chromosome loss, we identified 3 recurring chromosome losses (2F1-2, 3E4, 17E2) and two chromosome copy number gains on chromosome 11. These interstitial deletions and duplications were verified with a custom made array designed to interrogate the specific regions at approximately 550 bp resolution.

Results

We demonstrated that expression and genomic changes are present in the early premalignant lesions and that these molecular profiles can be correlated to phenotype (metastasis and estrogen responsiveness). We also identified expression changes associated with genomic instability. Progression to invasive carcinoma was associated with few additional changes in gene expression and genomic organization. Therefore, in the MIN-O mice, early premalignant lesions have the major molecular and genetic changes required and these changes have important phenotypic significance. In contrast, the changes that occur in the transition to invasive carcinoma are subtle, with few consistent changes and no association with phenotype.

Conclusion

We propose that the early lesions carry the important genetic changes that reflect the major phenotypic information, while additional genetic changes that accumulate in the invasive carcinoma are less associated with the overall phenotype.
Study protocol of a cluster randomised controlled trial investigating the effectiveness of a tailored energy balance programme for recent retirees
Authors: Werkman Andrea , Schuit Albertine J , Kwak Lydia , Kremers Stef PJ , Visscher Tommy LS , Kok Frans J , Schouten Evert G
Published: December 2006

Background

People in transitional life stages, such as occupational retirement, are likely to gain weight and accumulate abdominal fat mass caused by changes in physical activity and diet. Hence, retirees are an important target group for weight gain prevention programmes, as described in the present paper.

Methods/Design

A systematic and stepwise approach (Intervention Mapping) is used to develop a low-intensity energy balance intervention programme for recent retirees. This one-year, low-intensity multifaceted programme aims to prevent accumulation of abdominal fat mass and general weight gain by increasing awareness of energy balance and influencing related behaviours of participants' preference. These behaviours are physical activity, fibre intake, portion size and fat consumption. The effectiveness of the intervention programme is tested in a cluster randomised controlled trial. Measurements of anthropometry, physical activity, energy intake, and related psychosocial determinants are performed at baseline and repeated at 6 months for intermediate effect, at 12 months to evaluate short-term intervention effects and at 24 months to test the sustainability of the effects.

Discussion

This intervention programme is unique in its focus on retirees and energy balance. It aims at increasing awareness and takes into account personal preferences of the users by offering several options for behaviour change. Moreover, the intervention programme is evaluated at short-term and long-term and includes consecutive outcome measures (determinants, behaviour and body composition).
In vitro cell cultures obtained from different explants of Corylus avellanaproduce Taxol and taxanes
Authors: Bestoso Federica , Ottaggio Laura , Armirotti Andrea , Balbi Alessandro , Damonte Gianluca , Degan Paolo , Mazzei Mauro , Cavalli Francesca , Ledda Bernardetta , Miele Mariangela
Published: December 2006

Background

Taxol is an effective antineoplastic agent, originally extracted from the bark of Taxus brevifolia with a low yield. Many attempts have been made to produce Taxol by chemical synthesis, semi-synthesis and plant tissue cultures. However, to date, the availability of this compound is not sufficient to satisfy the commercial requirements. The aim of the present work was to produce suspension cell cultures from plants not belonging to Taxus genus and to verify whether they produced Taxol and taxanes. For this purpose different explants of hazel (Corylus avellana species) were used to optimize the protocol for inducing in vitro callus, an undifferentiated tissue from which suspension cell cultures were established.

Results

Calli were successfully induced from stems, leaves and seeds grown in various hormone concentrations and combinations. The most suitable callus to establish suspension cell cultures was obtained from seeds. Media recovered from suspension cell cultures contained taxanes, and showed antiproliferative activity on human tumour cells. Taxol, 10-deacetyltaxol and 10-deacetylbaccatin III were the main taxanes identified. The level of Taxol recovered from the media of hazel cultures was similar to that found in yew cultures. Moreover, the production of taxanes in hazel cell cultures increased when elicitors were used.

Conclusion

Here we show that hazel cell cultures produce Taxol and taxanes under controlled conditions. This result suggests that hazel possesses the enzymes for Taxol production, which until now was considered to be a pathway particular to Taxus genus. The main benefit of producing taxanes through hazel cell cultures is that hazel is widely available, grows at a much faster rate in vivo, and is easier to cultivate in vitro than yew. In addition, the production of callus directly from hazel seeds shortens the culture time and minimizes the probability of contamination. Therefore, hazel could become a commercial source of Taxol and taxanes, both to be used as new therapeutic agents or as new precursors for Taxol semi-synthesis.
P53 and p73 differ in their ability to inhibit glucocorticoid receptor (GR) transcriptional activity
Authors: Zhang Lili , Nie Linghu , Maki Carl G
Published: December 2006

Background

p53 is a tumor suppressor and potent inhibitor of cell growth. P73 is highly similar to p53 at both the amino acid sequence and structural levels. Given their similarities, it is important to determine whether p53 and p73 function in similar or distinct pathways. There is abundant evidence for negative cross-talk between glucocorticoid receptor (GR) and p53. Neither physical nor functional interactions between GR and p73 have been reported. In this study, we examined the ability of p53 and p73 to interact with and inhibit GR transcriptional activity.

Results

We show that both p53 and p73 can bind GR, and that p53 and p73-mediated transcriptional activity is inhibited by GR co-expression. Wild-type p53 efficiently inhibited GR transcriptional activity in cells expressing both proteins. Surprisingly, however, p73 was either unable to efficiently inhibit GR, or increased GR activity slightly. To examine the basis for this difference, a series of p53:p73 chimeric proteins were generated in which corresponding regions of either protein have been swapped. Replacing N- and C-terminal sequences in p53 with the corresponding sequences from p73 prevented it from inhibiting GR. In contrast, replacing p73 N- and C-terminal sequences with the corresponding sequences from p53 allowed it to efficiently inhibit GR. Differences in GR inhibition were not related to differences in transcriptional activity of the p53:p73 chimeras or their ability to bind GR.

Conclusion

Our results indicate that both N- and C-terminal regions of p53 and p73 contribute to their regulation of GR. The differential ability of p53 and p73 to inhibit GR is due, in part, to differences in their N-terminal and C-terminal sequences.
Antiphospholipid reactivity against cardiolipin metabolites occurring during endothelial cell apoptosis
Authors: Alessandri Cristiano , Sorice Maurizio , Bombardieri Michele , Conigliaro Paola , Longo Agostina , Garofalo Tina , Manganelli Valeria , Conti Fabrizio , Esposti Mauro Degli , Valesini Guido
Published: December 2006

We have recently shown that cardiolipin (CL) and its metabolites move from mitochondria to other cellular membranes during death receptor-mediated apoptosis. In this study, we investigate the immunoreactivity to CL derivatives occurring during endothelial apoptosis in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We compared the serum immunoreactivity to CL with that of its derivatives monolysocardiolipin (MCL), dilysocardiolipin (DCL), and hydrocardiolipin (HCL) by means of both enzyme-linked immunosorbent assay and thin-layer chromatography (TLC) immunostaining. In addition, we investigated the composition of phospholipid extracts from the plasma membrane of apoptotic endothelial cells and the binding of patients' sera to the surface of the same cells by using high-performance TLC and immunofluorescence analysis. The average reactivity to MCL was comparable with that of CL and significantly higher than that for DCL and HCL in patients studied, both in the presence or in the absence of beta2-glycoprotein I. Of relevance for the pathogenic role of these autoantibodies, immunoglobulin G from patients' sera showed an increased focal reactivity with the plasma membrane of endothelial cells undergoing apoptosis. Interestingly, the phospholipid analysis of these light membrane fractions showed an accumulation of both CL and MCL. Our results demonstrated that a critical number of acyl chains in CL derivatives is important for the binding of antiphospholipid antibodies and that MCL is an antigenic target with immunoreactivity comparable with CL in APS and SLE. Our finding also suggests a link between apoptotic perturbation of CL metabolism and the production of these antibodies.
Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages
Authors: Armani Chiara , Catalani Elisabetta , Balbarini Alberto , Bagnoli Paola , Cervia Davide
Published: December 2006

Somatostatin (SRIF)-14 is recognized as an important mediator between the nervous and the immune system, although the functional role of its receptors (sst1–sst5) is poorly understood in humans. In our study, we demonstrate that human macrophages, differentiated from PBMC-derived monocytes, express sst1 and sst2 mRNAs. sst1 and sst2 are mostly localized at the cell surface and display active binding sites. In particular, sst1/sst2 activation results in a weak internalization of sst1, and the sst2 internalization appears more efficient. At the functional level, the activation of SRIF receptors by the multiligand analogs SOM230 and KE108, but not by SRIF-14 or cortistatin-14, reduces macrophage viability. Their effects are mimicked by the selective activation of sst1 and sst2 using CH-275 and SMS 201-995/L-779,976, respectively. Further, sst1- and sst2-mediated effects are reversed by the sst1 antagonist SRA-880 or the sst2 antagonist CYN 154806, respectively. CH-275, SMS 201-995, and L-779,976, but not SRIF-14, decrease mRNA expression and secretion of the MCP-1. In addition, SRIF-14, CH-275, SMS 201-995, and L-779,976 decrease IL-8 secretion, and they do not affect IL-8 mRNA expression. In contrast, SRIF-14 and sst1/sst2 agonists do not affect the secretion of matrix metalloproteinase-9. Collectively, our results suggest that the SRIF system, through sst1 and sst2, exerts mainly an immunosuppressive effect in human macrophages and may, therefore, represent a therapeutic window that can be exploited for the development of new strategies in pharmacological therapy of inflammation.
Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C
Authors: Byrnes Adriana A , Li Ding-You , Park Kiwon , Thompson Douglas , Mocilnikar Cathleen , Mohan Parvathi , Molleston Jean P , Narkewicz Michael , Zhou Huanfang , Wolf Stanley F , Schwarz Kathleen B , Karp Christopher L
Published: December 2006

Although IFN-α forms the foundation of therapy for chronic hepatitis C, only a minority of patients has a sustained response to IFN-α alone. The antiviral activities of IFN-α formed the rationale for its use in viral hepatitis. However, IFN-α and the other Type I IFNs are also pleiotropic immune regulators. Type I IFNs can promote IFN-γ production by activating STAT4 but can also inhibit production of IL-12, a potent activator of STAT4 and IFN-γ production. The efficacy of IFN-α in the treatment of hepatitis C may therefore depend in part on the balance of IFN-γ-inducing and IL-12-suppressing effects. We characterized the effects of pegylated IFN-α therapy for hepatitis C on the capacity of patients’ PBMC to produce IL-12 and IFN-γ ex vivo. Cells from patients with a sustained virological response to therapy had significantly greater levels of IFN-α-driven IFN-γ production prior to treatment than those from nonresponding patients. No differences in pretreatment IL-12 productive capacity were seen between patient groups. However, therapy with IFN-α led to suppression of inducible IL-12 production throughout the course of therapy in both groups of patients.
Differences in Expression of Cardiovascular Risk Factors among Type 2 Diabetes Mellitus Patients of Different Age
Authors: KALOFOUTIS CHRISTOS , PIPERI CHRISTINA , ZISAKI AIKATERINI , SINGH JAIPAUL , HARRIS FRED , PHOENIX DAVID , ALAVERAS ANTONIS , KALOFOUTIS ANASTASIOS
Published: December 2006

Abstract:  Atherosclerotic coronary heart disease and other forms of cardiovascular disease (CVD) are the major cause of mortality in type II diabetes (T2DM) as well as a major contributor to morbidity and lifetime costs. The purpose of this article is the identification of the biochemical parameters in plasma, which may serve as predisposition factors to CVD in T2DM patients of different ages. The variability of hyperglycemia, dyslipidemia, and inflammation with age progression was also studied for comparison. Four different diabetic groups allocated on the basis of the subjects' age (Group A: 15–25 years old; Group B: 26–40 years old; Group C: 40–60 years old; Group D: 60–80 years old) and consisting of 10 patients each, in parallel with 10 healthy controls matched for age, sex, and ethnic origin were screened for glucose, insulin, lipid profile (total cholesterol, triglycerides, LDL, and HDL), and inflammatory mediators (CRP, IL‐6, and TNF‐α). Significant differences were observed among the expressions of biochemical markers among different age groups. Hyperglycemia showed no variability with age whereas dyslipidemia correlated positively with age progression, as well as obesity, low physical activity, and family history of heart disease or diabetes. Marked inflammation was prominent only in Groups C and D. This article indicates that different biochemical parameters may be used for the assessment of CVD risk in T2DM patients of variable age.
Blockade of the Renin–Angiotensin System Attenuates Sarcolemma and Sarcoplasmic Reticulum Remodeling in Chronic Diabetes
Authors: LIU XUELIANG , SUZUKI HIDEAKI , SETHI RAJAT , TAPPIA PARAMJIT S. , TAKEDA NOBUAKIRA , DHALLA NARANJAN S.
Published: December 2006

Abstract:  Although the defects in the sarcolemma (SL) and sarcoplasmic reticulum (SR) membranes are known to be associated with cardiac dysfunction in chronic diabetes, very little information regarding the mechanisms of these membrane abnormalities is available in the literature. For this reason, rats were treated daily for 8 weeks with and without enalapril, an angiotensin‐converting enzyme inhibitor, or losartan, an angiotensin receptor antagonist, 3 days after inducing diabetes with an injection of streptozocin. Treatment of diabetic animals with both enalapril and losartan attenuated alterations in cardiac function and the left ventricular redox potential without any changes in the increased plasma glucose or reduced plasma insulin levels. The SL Na+–K+ ATPase, Ca2+ pump, Na+‐dependent Ca2+‐uptake, Ca2+‐channel density, and low‐affinity Ca2+‐binding activities were depressed whereas Ca2+ ecto‐ATPase activity was increased in the diabetic heart. Furthermore, the SR Ca2+‐release and Ca2+‐pump activities in the diabetic hearts were decreased without any changes in the Mg2+‐ATPase activity. These alterations in SL and SR membranes in diabetic animals were partly prevented by treatments with enalapril and losartan. The results suggest that the activation of the renin–angiotensin system plays an important role in diabetes‐induced changes in SL and SR membranes as well as cardiac function.
Diabetic Neuropathy Differs in Type 1 and Type 2 Diabetes
Authors: SIMA ANDERS A.F. , KAMIYA HIDEKI
Published: December 2006

Abstract:  In this article we describe differences in early metabolic abnormalities between type 1 and type 2 diabetic polyneuropathy (DPN), and how these differences lead to milder initial functional defects in type 2 diabetes, despite the same hyperglycemic exposures. This early reversible metabolic phase is progressively overshadowed by structural degenerative changes eventually resulting in nerve fiber loss. In comparison, the late structural phase of DPN affects type 1 diabetes more severely. Progressive axonal atrophy and loss is hence expressed to a larger extent in type 1 diabetes. In addition, type 1 DPN is characterized by paranodal degenerative changes not seen in type 2 DPN. These differences can be related to the differences in insulin action and signal transduction affecting the expression of neurotrophic factors and their receptors in type 1 diabetes. Downstream effects on neuroskeletal and adhesive proteins, their posttranslational modifications, and nociceptive peptides underlie the more severe resultant pathology in type 1 DPN. These differences in underlying mechanisms should be seriously considered in the future design of interventional paradigms to combat these common conditions.
The Protective Effect of Tribulus terrestris in Diabetes
Authors: AMIN AMR , LOTFY MOHAMED , SHAFIULLAH MOHAMED , ADEGHATE ERNEST
Published: December 2006

Abstract: 
Tribulus terrestris L (TT) is used in the Arabic folk medicine to treat various diseases. The aim of this article was to investigate the protective effects of TT in diabetes mellitus (DM). Diabetes is known to increase reactive oxygen species (ROS) level that subsequently contributes to the pathogenesis of diabetes. Rats were divided into six groups and treated with either saline, glibenclamide (Glib), or TT for 30 days. Rats in group 1 were given saline after the onset of streptozotocin (STZ)‐induced diabetes; the second diabetic group was administered Glib (10 mg/kg body weight). The third diabetic group was treated with the TT extract (2 g/kg body weight), while the first, second, and third nondiabetic groups were treated with saline solution, Glib, and TT extract, respectively. At the end of the experiment, serum and liver samples were collected for biochemical and morphological analysis. Levels of serum alanine aminotransferase (ALT) and creatinine were estimated. In addition, levels of malondialdehyde (MDA) and reduced glutathione (GSH) were assayed in the liver. The tested TT extract significantly decreased the levels of ALT and creatinine in the serum (P < 0.05) in diabetic groups and lowered the MDA level in liver (P < 0.05) in diabetic and (P < 0.01) nondiabetic groups. On the other hand, levels of reduced GSH in liver were significantly increased (P < 0.01) in diabetic rats treated with TT. Histopathological examination revealed significant recovery of liver in herb‐treated rats. This investigation suggests that the protective effect of TT for STZ‐induced diabetic rats may be mediated by inhibiting oxidative stress.
Treatment of Diabetic Polyneuropathy
Authors: ZIEGLER DAN
Published: December 2006

Abstract:  At least one of four diabetic patients is affected by distal symmetric polyneuropathy (DSP), which represents a major health problem, as it may present with partly excruciating neuropathic pain and is responsible for substantial morbidity, increased mortality, and impaired quality of life. Treatment is based on four cornerstones: (a) causal treatment aimed at (near)‐normoglycemia, (b) treatment based on pathogenetic mechanisms, (c) symptomatic treatment, and (d) avoidance of risk factors and complications. Recent experimental studies suggest a multifactorial pathogenesis of diabetic neuropathy. From the clinical point of view it is important to note that, on the basis of these pathogenetic mechanisms, therapeutic approaches could be derived, some of which are currently being evaluated in clinical trials. Among these agents only α‐lipoic acid is available for treatment in several countries and epalrestat in Japan. Although several novel analgesic drugs, such as duloxetine and pregabalin, have recently been introduced into clinical practice, the pharmacological treatment of chronic painful diabetic neuropathy remains a challenge for the physician. Individual tolerability remains a major aspect in any treatment decision. Epidemiological data indicate that not only increased alcohol consumption but also the traditional cardiovascular risk factors, such as hypertension, smoking, and visceral obesity, play a role in development and progression of diabetic neuropathy and, hence, need to be prevented or treated.
Mucormycosis Mimicks Sinusitis in a Diabetic Adult
Authors: SZALAI GYÖRGY , FELLEGI VERONIKA , SZABÓ ZSUZSANNA , VITÉZ LAJOS CSOKONAI
Published: December 2006

Abstract:  Fungal sinusitis caused by invasive fungal infections, such as Mucormycosis, occurs predominantly in an immunocompromised patient. However, invasive cranial bone mycoses are rare and are usually associated with host immunodeficiency. They are difficult to diagnose, and in many cases are fatal. Treatment consists of antifungal chemotherapy, radical surgical debridement, and control of the underlying immunological condition. We report a case of Mucormycosis in a patient with type 1 diabetes mellitus. The patient had a history of dental pathology and associated renal dysfunction. The patient was managed by extensive surgical debridement followed by amphotericin B lipid complex injection (Abelcet 5 mg/bw kg/day) as an antifungal agent. Our patient's ocular function was affected. The radical treatment and follow‐up by a multidisciplinary team eliminated the mucor‐related consequences, however, the patient died because of end‐stage renal failure. In conclusion, type 1 diabetes may be associated with invasive fungal sinusitis.
Inflammation in Metabolic Syndrome and Type 2 Diabetes
Authors: KEMPF KERSTIN , ROSE BETTINA , HERDER CHRISTIAN , KLEOPHAS URSULA , MARTIN STEPHAN , KOLB HUBERT
Published: December 2006

Abstract:  Chronic overnutrition combined with a lack of exercise is the main cause for the rapidly increasing prevalence of overweight and obesity. It seems accepted that adipositis (macrophage infiltration and inflammation of adipose tissue in obesity) and systemic low grade inflammation affect the pathogenesis of the metabolic syndrome or type 2 diabetes mellitus (T2DM). Therefore, modern weight reduction programs additionally focus on strategies to attenuate the inflammation state. Exercise is one major factor, which contributes to the reduction of both the incidence of T2DM and inflammation, and the immunomodulatory effects of exercise are supported by similarly beneficial effects of dietary changes. In this context, glucose is the most extensively studied nutrient and current investigations focus on postprandial glucose‐induced inflammation, one possible reason why hyperglycemia is detrimental. Indeed, glucose may modulate the mRNA expression and serum concentrations of immune parameters but these alterations rapidly normalize in normoglycemic subjects. In case of an impaired metabolic state, however, postprandial hyperglycemia increases magnitude and duration of systemic inflammatory responses, which probably promotes the development of T2DM and of cardiovascular disease.