bluuebunny/crossref_metadata_2025 huggingface dataset:
RBM6-RBM5 transcription-induced chimeras are differentially expressed in tumours
Authors: Wang Ke , Ubriaco Gino , Sutherland Leslie C
Published: October 2007

Background

Transcription-induced chimerism, a mechanism involving the transcription and intergenic splicing of two consecutive genes, has recently been estimated to account for ~5% of the human transcriptome. Despite this prevalence, the regulation and function of these fused transcripts remains largely uncharacterised.

Results

We identified three novel transcription-induced chimeras resulting from the intergenic splicing of a single RNA transcript incorporating the two neighbouring 3p21.3 tumour suppressor locus genes, RBM6 and RBM5, which encode the RNA Binding Motif protein 6 and RNA Binding Motif protein 5, respectively. Each of the three novel chimeric transcripts lacked exons 3, 6, 20 and 21 of RBM6 and exon 1 of RBM5. Differences between the transcripts were associated with the presence or absence of exon 4, exon 5 and a 17 nucleotide (nt) sequence from intron 10 of RBM6. All three chimeric transcripts incorporated the canonical splice sites from both genes (excluding the 17 nt intron 10 insertion). Differential expression was observed in tumour tissue compared to non-tumour tissue, and amongst tumour types. In breast tumour tissue, chimeric expression was associated with elevated levels of RBM6 and RBM5 mRNA, and increased tumour size. No protein expression was detected by in vitro transcription/translation.

Conclusion

These results suggest that RBM6 mRNA experiences altered co-transcriptional gene regulation in certain cancers. The results also suggest that RBM6-RBM5 transcription-induced chimerism might be a process that is linked to the tumour-associated increased transcriptional activity of the RBM6 gene. It appears that none of the transcription-induced chimeras generates a protein product; however, the novel alternative splicing, which affects putative functional domains within exons 3, 6 and 11 of RBM6, does suggest that the generation of these chimeric transcripts has functional relevance. Finally, the association of chimeric expression with breast tumour size suggests that RBM6-RBM5 chimeric expression may be a potential tumour differentiation marker.
Cadmium triggers an integrated reprogramming of the metabolism of Synechocystis PCC6803, under the control of the Slr1738 regulator
Authors: Houot Laetitia , Floutier Martin , Marteyn Benoit , Michaut Magali , Picciocchi Antoine , Legrain Pierre , Aude Jean-Christophe , Cassier-Chauvat Corinne , Chauvat Franck
Published: October 2007

Background

Cadmium is a persistent pollutant that threatens most biological organisms, including cyanobacteria that support a large part of the biosphere. Using a multifaceted approach, we have investigated the global responses to Cd and other relevant stresses (H2O2and Fe) in the model cyanobacteriumSynechocystisPCC6803.

Results

We found that cells respond to the Cd stress in a two main temporal phases process. In the "early" phase cells mainly limit Cd entry through the negative and positive regulation of numerous genes operating in metal uptake and export, respectively. As time proceeds, the number of responsive genes increases. In this "massive" phase, Cd downregulates most genes operating in (i) photosynthesis (PS) that normally provides ATP and NADPH; (ii) assimilation of carbon, nitrogen and sulfur that requires ATP and NAD(P)H; and (iii) translation machinery, a major consumer of ATP and nutrients. Simultaneously, many genes are upregulated, such as those involved in Fe acquisition, stress tolerance, and protein degradation (crucial to nutrients recycling). The most striking common effect of Cd and H2O2is the disturbance of both light tolerance and Fe homeostasis, which appeared to be interdependent. Our results indicate that cells challenged with H2O2or Cd use different strategies for the same purpose of supplying Fe atoms to Fe-requiring metalloenzymes and the SUF machinery, which synthesizes or repairs Fe-S centers. Cd-stressed cells preferentially breakdown their Fe-rich PS machinery, whereas H2O2-challenged cells preferentially accelerate the intake of Fe atoms from the medium.

Conclusion

We view the responses to Cd as an integrated "Yin Yang" reprogramming of the whole metabolism, we found to be controlled by the Slr1738 regulator. As the Yin process, the ATP- and nutrients-sparing downregulation of anabolism limits the poisoning incorporation of Cd into metalloenzymes. As the compensatory Yang process, the PS breakdown liberates nutrient assimilates for the synthesis of Cd-tolerance proteins, among which we found the Slr0946 arsenate reductase enzyme.
Production of L-carnitine by secondary metabolism of bacteria
Authors: Bernal Vicente , Sevilla Ángel , Cánovas Manuel , Iborra José L
Published: October 2007

The increasing commercial demand for L-carnitine has led to a multiplication of efforts to improve its production with bacteria. The use of different cell environments, such as growing, resting, permeabilized, dried, osmotically stressed, freely suspended and immobilized cells, to maintain enzymes sufficiently active for L-carnitine production is discussed in the text. The different cell states of enterobacteria, such asEscherichia coliandProteus sp., which can be used to produce L-carnitine from crotonobetaine or D-carnitine as substrate, are analyzed. Moreover, the combined application of both bioprocess and metabolic engineering has allowed a deeper understanding of the main factors controlling the production process, such as energy depletion and the alteration of the acetyl-CoA/CoA ratio which are coupled to the end of the biotransformation. Furthermore, the profiles of key central metabolic activities such as the TCA cycle, the glyoxylate shunt and the acetate metabolism are seen to be closely interrelated and affect the biotransformation efficiency. Although genetically modified strains have been obtained, new strain improvement strategies are still needed, especially inEscherichia colias a model organism for molecular biology studies. This review aims to summarize and update the state of the art in L-carnitine production usingE. coliandProteus sp, emphasizing the importance of proper reactor design and operation strategies, together with metabolic engineering aspects and the need for feed-back betweenwetandin silicowork to optimize this biotransformation.
Altered expression pattern of integrin alphavbeta3 correlates with actin cytoskeleton in primary cultures of human breast cancer
Authors: Havaki Sophia , Kouloukoussa Mirsini , Amawi Kawther , Drosos Yiannis , Arvanitis Leonidas D , Goutas Nikos , Vlachodimitropoulos Dimitrios , Vassilaros Stamatis D , Katsantoni Eleni Z , Voloudakis-Baltatzis Irene , Aleporou-Marinou Vassiliki , Kittas Christos , Marinos Evangelos
Published: October 2007

Background

Integrins are transmembrane adhesion receptors that provide the physical link between the actin cytoskeleton and the extracellular matrix. It has been well established that integrins play a major role in various cancer stages, such as tumor growth, progression, invasion and metastasis. In breast cancer, integrin alphavbeta3 has been associated with high malignant potential in cancer cells, signaling the onset of widespread metastasis. Many preclinical breast cancer studies are based on established cell lines, which may not represent the cell behavior and phenotype of the primary tumor of origin, due to undergone genotypic and phenotypic changes. In the present study, short-term primary breast cancer cell cultures were developed. Integrin alphavbeta3 localization was studied in correlation with F-actin cytoskeleton by means of immunofluorescence and immunogold ultrastructural localization. Integrin fluorescence intensities were semi-quantitatively assessed by means of computerized image analysis, while integrin and actin expression was evaluated by Western immunoblotting.

Results

In the primary breast cancer epithelial cells integrin alphavbeta3 immunofluorescence was observed in the marginal cytoplasmic area, whereas in the primary normal breast epithelial cells it was observed in the main cell body, i.e. in the ventrally located perinuclear area. In the former, F-actin cytoskeleton appeared well-formed, consisting of numerous and thicker stress fibers, compared to normal epithelial cells. Furthermore, electron microscopy showed increased integrin alphavbeta3 immunogold localization in epithelial breast cancer cells over the area of stress fibers at the basal cell surface. These findings were verified with Western immunoblotting by the higher expression of integrin beta3 subunit and actin in primary breast cancer cells, revealing their reciprocal relation, in response to the higher motility requirements, determined by the malignant potential of the breast cancer cells.

Conclusion

A model system of primary breast cancer cell cultures was developed, in an effort to maintain the closest resembling environment to the tumor of origin. Using the above system model as an experimental tool the study of breast tumor cell behavior is possible concerning the adhesion capacity and the migrating potential of these cells, as defined by the integrin alphavbeta3 distribution in correlation with F-actin cytoskeleton.
PCR-based karyotyping of Anopheles gambiae inversion 2Rj identifies the BAMAKO chromosomal form
Authors: Coulibaly Mamadou B , Pombi Marco , Caputo Beniamino , Nwakanma Davis , Jawara Musa , Konate Lassana , Dia Ibrahima , Fofana Abdrahamane , Kern Marcia , Simard Frédéric , Conway David J , Petrarca Vincenzo , Torre Alessandra della , Traoré Sékou , Besansky Nora J
Published: October 2007

Background

The malaria vector Anopheles gambiae is polymorphic for chromosomal inversions on the right arm of chromosome 2 that segregate nonrandomly between assortatively mating populations in West Africa. One such inversion, 2Rj, is associated with the BAMAKO chromosomal form endemic to southern Mali and northern Guinea Conakry near the Niger River. Although it exploits a unique ecology and both molecular and chromosomal data suggest reduced gene flow between BAMAKO and other A. gambiae populations, no molecular markers exist to identify this form.

Methods

To facilitate study of the BAMAKO form, a PCR assay for molecular karyotyping of 2Rj was developed based on sequences at the breakpoint junctions. The assay was extensively validated using more than 700 field specimens whose karyotypes were determined in parallel by cytogenetic and molecular methods. As inversion 2Rj also occurs in SAVANNA populations outside the geographic range of BAMAKO, samples were tested from Senegal, Cameroon and western Guinea Conakry as well as from Mali.

Results

In southern Mali, where 2Rj polymorphism in SAVANNA populations was very low and most of the 2Rj homozygotes were found in BAMAKO karyotypes, the molecular and cytogenetic methods were almost perfectly congruent. Elsewhere agreement between the methods was much poorer, as the molecular assay frequently misclassified 2Rj heterozygotes as 2R+j standard homozygotes.

Conclusion

Molecular karyotyping of 2Rj is robust and accurate on 2R+j standard and 2Rj inverted homozygotes. Therefore, the proposed approach overcomes the lack of a rapid tool for identifying the BAMAKO form across developmental stages and sexes, and opens new perspectives for the study of BAMAKO ecology and behaviour. On the other hand, the method should not be applied for molecular karyotyping of j-carriers within the SAVANNA chromosomal form.
Detection, characterization and regulation of antisense transcripts in HIV-1
Authors: Landry Sébastien , Halin Marilène , Lefort Sylvain , Audet Brigitte , Vaquero Catherine , Mesnard Jean-Michel , Barbeau Benoit
Published: October 2007

Background

We and others have recently demonstrated that the human retrovirus HTLV-I was producing a spliced antisense transcript, which led to the synthesis of the HBZ protein. The objective of the present study was to demonstrate the existence of antisense transcription in HIV-1 and to provide a better characterization of the transcript and its regulation.

Results

Initial experiments conducted by standard RT-PCR analysis in latently infected J1.1 cell line and pNL4.3-transfected 293T cells confirmed the existence of antisense transcription in HIV-1. A more adapted RT-PCR protocol with limited RT-PCR artefacts also led to a successful detection of antisense transcripts in several infected cell lines. RACE analyses demonstrated the existence of several transcription initiation sites mapping near the 5' border of the 3'LTR (in the antisense strand). Interestingly, a new polyA signal was identified on the antisense strand and harboured the polyA signal consensus sequence. Transfection experiments in 293T and Jurkat cells with an antisense luciferase-expressing NL4.3 proviral DNA showed luciferase reporter gene expression, which was further induced by various T-cell activators. In addition, the viral Tat protein was found to be a positive modulator of antisense transcription by transient and stable transfections of this proviral DNA construct. RT-PCR analyses in 293T cells stably transfected with a pNL4.3-derived construct further confirmed these results. Infection of 293T, Jurkat, SupT1, U937 and CEMT4 cells with pseudotyped virions produced from the antisense luciferase-expressing NL4.3 DNA clone led to the production of an AZT-sensitive luciferase signal, which was however less pronounced than the signal from NL4.3Luc-infected cells.

Conclusion

These results demonstrate for the first time that antisense transcription exists in HIV-1 in the context of infection. Possible translation of the predicted antisense ORF in this transcript should thus be re-examined.
Morphine Reduces Local Cytokine Expression and Neutrophil Infiltration after Incision
Authors: Clark J David , Shi Xiaoyou , Li Xiangqi , Qiao Yanli , Liang DeYong , Angst Martin S , Yeomans David C
Published: October 2007

Background:

Inflammation and nociceptive sensitization are hallmarks of tissue surrounding surgical incisions. Recent studies demonstrate that several cytokines may participate in the enhancement of nociception near these wounds. Since opioids like morphine interact with neutrophils and other immunocytes, it is possible that morphine exerts some of its antinociceptive action after surgical incision by altering the vigor of the inflammatory response. On the other hand, keratinocytes also express opioid receptors and have the capacity to produce cytokines after injury. Our studies were directed towards determining if opioids alter cytokine production near incisions and to identify cell populations responsible for producing these cytokines.

Results:

A murine incisional model was used to measure the effects of acute morphine administration (0.1–10 mg/kg) on nociceptive thresholds, neutrophil infiltration and cytokine production in hind paw skin 30 minutes and 2 hours after incision. Incised hind paws displayed profound allodynia which was reduced by morphine (0.1–10 mg/kg) in the 2 hours following incision. Skin samples harvested from these mice showed enhanced levels of 5 cytokines: IL-1β, IL-6, tumor necrosis factor alpha (TNFα), granulocyte colony stimulating factor (G-CSF) and keratinocyte-derived cytokine (KC). Morphine reduced these incision-stimulated levels. Separate analyses measuring myeloperoxidase (MPO) and using immunohistochemistry demonstrated that morphine dose-dependently reduced the infiltration of neutrophils into the peri-incisional tissue. The dose of morphine required for reduction of cytokine accumulation, however, was below that required for inhibition of peri-incisional neutrophil infiltration. Additional immunohistochemical studies revealed wound edge keratinocytes as being an important source of cytokines in the acute phase after incision.

Conclusion:

Acute morphine administration of doses as low as 0.1 mg/kg reduces peri-incisional cytokine expression. A reduction in neutrophil infiltration does not provide a complete explanation for this effect, and keratinocytes may be responsible for some incision area cytokine production. These studies suggest that morphine may alter the inflammatory milieu of incisional wounds, but these alterations do not likely contribute significantly to analgesia in the acute setting.
Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas
Authors: Kreike Bas , van Kouwenhove Marieke , Horlings Hugo , Weigelt Britta , Peterse Hans , Bartelink Harry , van de Vijver Marc J
Published: October 2007

Introduction

Breast cancer is a heterogeneous group of tumors, and can be subdivided on the basis of histopathological features, genetic alterations and gene-expression profiles. One well-defined subtype of breast cancer is characterized by a lack of HER2 gene amplification and estrogen and progesterone receptor expression ('triple-negative tumors'). We examined the histopathological and gene-expression profile of triple-negative tumors to define subgroups with specific characteristics, including risk of developing distant metastases.

Methods

97 triple-negative tumors were selected from the fresh-frozen tissue bank of the Netherlands Cancer Institute, and gene-expression profiles were generated using 35K oligonucleotide microarrays. In addition, histopathological and immunohistochemical characterization was performed, and the findings were associated to clinical features.

Results

All triple-negative tumors were classified as basal-like tumors on the basis of their overall gene-expression profile. Hierarchical cluster analysis revealed five distinct subgroups of triple-negative breast cancers. Multivariable analysis showed that a large amount of lymphocytic infiltrate (HR = 0.30, 95% CI 0.09–0.96) and absence of central fibrosis in the tumors (HR = 0.14, 95% CI 0.03–0.62) were associated with distant metastasis-free survival.

Conclusion

Triple-negative tumors are synonymous with basal-like tumors, and can be identified by immunohistochemistry. Based on gene-expression profiling, basal-like tumors are still heterogeneous and can be subdivided into at least five distinct subgroups. The development of distant metastasis in basal-like tumors is associated with the presence of central fibrosis and a small amount of lymphocytic infiltrate.
Immunoglobulin‐like Transcripts as Risk Genes for Autoimmunity
Authors: KABALAK GAMZE , KOCH SILKE , DOBBERSTEIN BAUKJE , THE YU‐HAN , MATTHIAS TORSTEN , SCHNARR SEBASTIAN , SCHMIDT REINHOLD E. , WITTE TORSTEN
Published: October 2007

Abstract:  Risk genes for multiple sclerosis (MS) are localized in the gene regions 6p21‐11 and 19q13, the latter harboring the genes of the immunoglobulin‐like transcripts (ILTs). ILTs are a family of activating and inhibitory receptors expressed on antigen‐presenting cells (APCs) as well as on natural killer (NK) and T cells. Because of the inhibitory function of ILT2 and ILT4 and their binding to human leukocyte antigen (HLA)‐G, they play a role in immune tolerance and may be important in pathogenesis of autoimmunity. ILT6 shows presence–absence variability and is produced by macrophages in a soluble form. ILT6 deletion is associated with MS. Furthermore, ILT6 activates T cell proliferation and is therefore a candidate gene for autoimmune disorders.
“B27 Disease” Is a New Autoimmune Disease That Affects Millions of People
Authors: EBRINGER ALAN , RASHID TAHA
Published: October 2007

Abstract:  “B27 disease” is a new autoimmune disease that afflicts millions of people throughout the world. “B27 disease” occurs in individuals who have ankylosing spondylitis (AS) or preankylosing spondylitis and/or uveitis and are also positive for HLA‐B27. Molecular mimicry between the bowel microbe Klebsiella and the HLA‐B27 molecule, as well as the spinal collagens types I, III, and IV, indicates a pathological mechanism involving autoimmunity. Antibodies to Klebsiella microbes have been reported in AS patients from 18 different countries. Sera from patients with AS show complement‐dependent cytopathic activity against sheep red cells coated with HLA‐B27 peptide antigens. Diagnosis of B27 disease can lead to early treatment, involving low‐starch diet, sulfasalazine, and immunosuppressive and biological agents so as to prevent the irreversible bony changes of established classical AS. The concept of B27 disease provides a new approach to the study and treatment of these disorders and needs to be evaluated in prospective studies by the world rheumatological community.
Association of the 5A/6A Promoter Polymorphism of the MMP‐3 Gene with the Radiographic Progression of Rheumatoid Arthritis
Authors: NEMEC PETR , PAVKOVA‐GOLDBERGOVA MONIKA , GATTEROVA JINDRA , VASKU ANNA , SOUCEK MIROSLAV
Published: October 2007

Abstract:  Matrix metalloproteinases (MMPs) as a family of zinc‐dependent endopeptidases have been involved in remodeling the extracellular matrix (ECM) in rheumatoid arthritis (RA). In RA patients synovial fluid and serum include enhanced levels of MMP‐3. The 5A/6A polymorphism in the MMP‐3 gene promoter can contribute to the severity of RA on account of a higher promoter activity of the 5A allele in vitro. The aim of the study was to associate the 5A/6A polymorphism of the MMP‐3 gene with radiographic progression of RA. A total of 128 RA patients according to the ACR criteria were available for the study. Radiographs of both hands, obtained from all RA patients, were scored using the modified Sharp/van der Heijde method and the Steinbrocker method. The total Sharp score (TSS) and the annual radiographic progression rate (TSS/year) were calculated. Significant association with the 5A/6A polymorphism was found between patients with TSS/year ≤ 1.00 and those with TSS/year > 1.00 in allelic frequencies (Pa= 0.046) and also in genotype distribution (Pg= 0.04). Compared to other genotypes the prevalence of 5A/5A genotype was lower within patients with TSS/year ≤ 1.00 (odds ratio [OR]= 0.2; 95% confidence interval [CI] 0.04–0.85; P= 0.01). Also, in comparison to genotypes 5A/6A and 5A/5A, the prevalence of 6A/6A genotype was higher within patients with nonerosive RA (OR = 2.65; 95% CI 1.03–6.83, P= 0.02). Results obtained in this study provide the evidence of an association of the 5A/6A promoter polymorphism of the MMP‐3 gene to the radiographic progression of RA.
Thyroid Epigenetics
Authors: YIN XIAOMING , LATIF RAUF , TOMER YARON , DAVIES TERRY F.
Published: October 2007

Abstract:  The autoimmune thyroid diseases (AITDs) are female‐predominant diseases with a ratio of approximately seven females to each male. X chromosome inactivation (XCI), an epigenetic phenomenon, has been suggested to be skewed in many such female patients with AITD. We analyzed female genomic DNA from 87 patients with Graves' disease (GD), 47 patients with Hashimoto's thyroiditis (HT), and 69 healthy controls. Using an XCI assay based on Hpa II digestion and PCR and DNA sequencing, we found skewed heterozygous XCI (≥80%) in 20 of 70 GD patients (28.6%) and 11 of 43 HT patients (25.6%), giving a total of 31 of 113 AITD patients (27.4%) with skewed XCI. In contrast, only 5 of 58 healthy controls had skewed XCI (8.6%). Statistical analysis confirmed that XCI skewing was significantly associated with AITD (P= 0.004, OR = 4.0), demonstrating that the degree of XCI is an important contributor to the increased risk of females in developing AITD.
CD44 Involvement in Autoimmune Inflammations
Authors: NAOR DAVID , NEDVETZKI SHLOMO , WALMSLEY MARITA , YAYON AVNER , TURLEY EVA A. , GOLAN IRA , CASPI DAN , SEBBAN LORA ESHKAR , ZICK YEHIEL , GARIN TALI , KARUSSIS DIMITRIOS , ASSAYAG‐ASHERIE NATHALIE , RAZ ITAMAR , WEISS LOLA , SLAVIN SHIMON , GOLAN ITSHAK
Published: October 2007

Abstract:  CD44 is a multistructural and multifunctional glycoprotein, the diversity of which is generated by alternative splicing. In this communication we review some aspects related to CD44 structure and function in experimental autoimmune inflammation, focusing on research performed in our own laboratory. We have found that CD44 targeting by antibody, passively injected into DBA/1 mice with collagen‐induced arthritis (CIA) and NOD mice with type I diabetes or actively generated by CD44 cDNA vaccination of SJL/j mice with autoimmune encephalomyelitis, markedly reduced the pathological manifestations of these diseases by attenuating cell migration of the inflammatory cells and/or by their apoptotic killing. However, genetic deletion of CD44 by knockout technology enhanced the development of CIA because of molecular redundancy mediated by RHAMM (a receptor of hyaluronan‐mediated motility). The mechanisms that stand behind these findings are discussed.
Efficacy of Intravenous Immunoglobulin in Multifocal Motor Neuropathy
Authors: LEGER JEAN‐MARC , VARGAS STEVEN , LIEVENS ISABELLE
Published: October 2007

Abstract:  Multifocal motor neuropathy is a distinct entity, whose treatment differs from that of other chronic immune‐mediated neuropathies, mainly chronic inflammatory demyelinating polyradiculoneuropathy, and its variant, multifocal acquired demyelinating sensory and motor neuropathy, although they share some electrophysiological characteristics. From the first descriptions, intravenous immunoglobulins (IVIg) have been considered to be the gold standard of treatment for multifocal motor neuropathy. However, if the effectiveness of IVIg has been confirmed by several randomized, double‐blind, placebo‐controlled trials, only a few patients experience persistent improvement after a single or few courses of therapy, and the long‐term efficacy of IVIg in this disease is currently debated. Consequently, there is a need for new therapeutic strategies that focus on the effects and the costs of this therapy over long‐term follow‐up.
New Autoantibodies in Pediatric Opsoclonus–Myoclonus Syndrome
Authors: KIRSTEN A. , BECK S. , FÜHLHUBER V. , KAPS M. , KREUTZ T. , KORFEI M. , SCHMITT S. , PREISSNER K.T. , BLAES F.
Published: October 2007

Abstract:  Opsoclonus–myoclonus syndrome (OMS) is a rare neurologic disorder comprising the main symptoms of eye‐movement disturbances, muscle jerks, and severe ataxia. In children and adults, some cases are associated with a tumor as a paraneoplastic syndrome, whereas in children the paraneoplastic form is almost exclusively associated with neuroblastoma. The detection of autoantibodies in some OMS sera led to the hypothesis that the syndrome is of autoimmune origin. Beside autoantibodies against intracellular proteins, such as anti‐Hu, α‐enolase, and KHSRP, specific binding of autoantibodies to the surface of neuroblastoma cells and cerebellar granular neurons have been found. Antiproliferative and proapoptotic effects of these autoantibodies on neuroblastoma cell lines were noted as well. These results support the concept of a humoral autoimmune process in the pathogenesis of OMS.
Intravenous Immunoglobulin and Autoimmune Disease
Authors: EL‐SHANAWANY TARIQ , JOLLES STEPHEN
Published: October 2007

Abstract:  Intravenous immunoglobulin (IVIg) has been found to have a multitude of uses. However, IVIg is a pooled blood product and as a result a limited resource. At replacement doses (200–400 mg/kg/month) it is of critical utility in the treatment of primary and secondary antibody deficiencies. High‐dose immunoglobulin (hdIVIg) given at doses of up to 2 g/kg/day has immunomodulatory action mediated via a number of different effects. First used in the 1980s for the treatment of idiopathic thrombocytopenic purpura, hdIVIg has found uses in a wide range of autoimmune conditions, though for many conditions the evidence base lacks formal randomized controlled trials (RCTs). This article will detail the issues regarding the manufacture and clinical aspects of administration of hdIVIg and its uses, especially with regards to the treatment of autoimmune disease.
Attenuation of Colon Carcinoma Tumor Spread by Intravenous Immunoglobulin
Authors: DAMIANOVICH MAYA , SOLOMON ARIEH SORIN , BLANK MIRI , SHOENFELD YEHUDA
Published: October 2007

Abstract:  The impact of IVIg on metastatic capacity of CT26 murine colon carcinoma cells was studied using in vitro and in vivo methods. IVIg inhibited CT26 cell proliferation and invasion through an extracellular matrix in a dose‐ and time‐dependent manner. Systemic treatment of mice with IVIg significantly inhibited metastatic potential of CT26 colon carcinoma cells observed as tumor nodules and lung weight reduction. Treating CT26 cell‐implanted rabbit corneas with IVIg led to shrinking and complete disappearance of tumor mass in 10 days. These results provide the evidence that IVIg may be considered as a supportive therapy for inhibition of colon carcinoma tumor spread.
A New Orally Bioavailable Synthetic Androstene Inhibits Collagen‐Induced Arthritis in the Mouse
Authors: AUCI D. , KALER L. , SUBRAMANIAN SANDHYA , HUANG YUGIN , FRINCKE J. , READING C. , OFFNER H.
Published: October 2007

Abstract:  Dehydroepiandrosterone (DHEA) has attracted much interest because of its many antiaging, metabolic and immune‐modulating effects in rodents. Synthetic derivatives, such as 5‐androstene‐16α‐fluoro‐17‐one (HE2500) and certain natural metabolites also provide benefit in various animal models of autoimmune and metabolic diseases. But, like DHEA, low potency and low oral bioavailability suggested limited usefulness of these compounds in humans. We hypothesized that HE3286, a novel 17‐ethynyl derivative would be orally bioavailable, more potent, and chemically more useful in man than its parent compound. We found that on a dose/mass basis, HE3286 demonstrated up to 25% oral bioavailability in mice. In the DBA mouse model of collagen‐induced arthritis (CIA), animals receiving oral treatment with HE3286 (50 mg/kg), beginning at onset of disease, significantly decreased CIA peak scores and daily severity of arthritis scores. Benefit was associated with decreases in: (1) production of TNF‐α, IL‐6, and IL‐17; and (2) decreases in joint inflammation, erosion, and synovial proliferation as judged by histological analysis. HE3286 was not found to be immune suppressive in any of the classical models tested, including mitogen‐induced proliferation, delayed‐type hypersensitivity, or mixed lymphocyte reaction. Instead, benefit was associated with increases in numbers and function of CD4+CD25+FOXp3+CD127– regulatory T cells (Treg). To our knowledge, this is probably the first study to report that an orally bioavailable synthetic analogue of DHEA can ameliorate ongoing disease in a CIA mouse model with relevance to rheumatoid arthritis (RA) and to correlate that finding with decreases in proinflammatory cytokines and increases in Treg cells. Hormones targeting Treg cells hold the intriguing potential to treat autoimmune, infectious, and neoplastic diseases.
Mechanism of Action of IFN‐β in the Treatment of Multiple Sclerosis
Authors: AIRAS LAURA , NIEMELÄ JUSSI , YEGUTKIN GENNADY , JALKANEN SIRPA
Published: October 2007

Abstract:  IFN‐β treatment reduces the relapse rate in multiple sclerosis (MS), but the exact mechanism of action of the drug has remained elusive. CD73 (ecto‐5′‐nucleotidase) is an ectoenzyme, which produces adenosine from adenosine monophosphate (AMP) precursor by enzymatic dephosphorylation. AMP is known to be abundantly present at sites of inflammation, and more importantly adenosine, the product of CD73, is known to possess both anti‐inflammatory and neuroprotective activity. Our preliminary work has shown that IFN‐β increases the expression of ecto‐5′‐nucleotidase on endothelial cells (ECs) both in vitro and after systemic treatment of MS patients in vivo. In the majority of MS patients also an increase in the soluble serum CD73 was noted after IFN‐β treatment. Importantly, this correlated with the clinical outcome. CD73 expression on central nervous system (CNS) microvasculature was confirmed with stainings of frozen tissue sections of MS brain samples taken at autopsy. Adenosine, a known neuroprotective agent, might contribute to the beneficial effects of IFN‐β on MS.
Antifungal Prophylaxis in Cancer Patients After Chemotherapy or Hematopoietic Stem-Cell Transplantation: Systematic Review and Meta-Analysis
Authors: Robenshtok Eyal , Gafter-Gvili Anat , Goldberg Elad , Weinberger Miriam , Yeshurun Moshe , Leibovici Leonard , Paul Mical
Published: October 2007

Purpose

To evaluate the effect of antifungal prophylaxis on all-cause mortality as primary outcome, invasive fungal infections (IFIs), and adverse events. Many studies have evaluated the role of antifungal prophylaxis in cancer patients, with inconsistent conclusions.

Methods

We performed a systematic review and meta-analysis of randomized, controlled trials comparing systemic antifungals with placebo, no intervention, or other antifungal agents for prophylaxis in cancer patients after chemotherapy. The Cochrane Library, MEDLINE, conference proceedings, and references were searched. Two reviewers independently appraised the quality of trials and extracted data.

Results

Sixty-four trials met inclusion criteria. Antifungal prophylaxis decreased all-cause mortality significantly at end of follow-up compared with placebo, no treatment, or nonsystemic antifungals (relative risk [RR], 0.84; 95% CI, 0.74 to 0.95). In allogeneic hematopoietic stem-cell transplantation (HSCT) recipients, prophylaxis reduced all-cause mortality (RR, 0.62; 95% CI, 0.45 to 0.85), fungal-related mortality, and documented IFI. In acute leukemia patients, there was a significant reduction in fungal-related mortality and documented IFI, whereas the difference in mortality was only borderline significant (RR, 0.88; 95% CI, 0.74 to 1.06). Prophylaxis with itraconazole suspension reduced documented IFI when compared with fluconazole, with no difference in survival, and at the cost of more adverse events. On the basis of two studies, posaconazole prophylaxis reduced all-cause mortality (RR, 0.74; 95% CI, 0.56 to 0.98), fungal-related mortality, and IFI when compared with fluconazole.

Conclusion

Antifungal prophylaxis decreases all-cause mortality significantly in patients after chemotherapy. Antifungal prophylaxis should be administered to patients undergoing allogeneic HSCT, and should probably be administered to high-risk acute leukemia patients.
“We” In Redux: The Combahee River Collective'sBlack Feminist Statement
Authors: Norman Brian
Published: October 2007

brian norman is Assistant Professor of English and Director of Women's Studies at Idaho State University where he specializes in twentieth-century literature, especially African American, feminist, and multiethnic u.s. literatures. His current research examines contemporary literary representations of race segregation. He is guest editor of a forthcoming special issue of African American Review, on Representing Segregation. He is the author of The American Protest Essay and National Belonging: Addressing Division (suny Press, 2007), and recent articles have appeared in African American Review, Canadian Review of American Studies, Frontiers,melus, and Women's Studies.
The Inventions of Edward Geisler Herbert
Authors: Herbert T. M.
Published: October 2007

This autobiographical note was written by Edward Herbert a few years before his death, and gives an account of a lifetime devoted to research, mainly on the hardness and machinability of metals. Though taking an important part in the engineering business that bore his name, Herbert was essentially a research worker rather than a business man, and towards the close of his life he withdrew more and more into the laboratory which he had equipped at his home.

The present note emphasizes the continuity of Herbert's work. Thus his original automatic saw was converted into the first experimental file testing machine; the study of the cutting action of file teeth suggested the tool steel tester, the anomalous results of which led to the tool-work thermocouple and the “Pendulum” hardness tester. Then followed in logical sequence his work on critical work-hardening temperatures, the work-hardening capacity of hard steels, the “Cloudburst” process, the age-hardening of superhardened steel, periodic ageing fluctuations and the effects of magnetic treatments; and finally, the invention of the continuous hardness tester and the scanning of diamond scratches as a means of recording fluctuations in hardness due to ageing.
The Modern Paper-Making Machine
Authors: Orr W. H.
Published: October 2007

During the last two decades both the speed and width of paper machines have increased considerably. This has resulted in the adoption of many devices which prior to that time were still looked on with doubt. The increase in width and weight of the rolls of modern newsprint machines has made the removable wet end practically standard. Similarly the increase in speed has only been made possible by the use of the projection slice, suction couch, and press rolls, which are being fitted with success to machines of all types.

The shells of suction rolls must be free from blowholes and this has entailed the use of centrifugal castings, and has been the means of developing their technique. A further development is the vacuum-forming paper machine, probably the most revolutionary modification of the Fourdrinier machine yet proposed. The two-wire machine gives a paper free from any wire mark, and recently a wire has been produced which goes some way towards the elimination of the wire mark. Electric drives arc nearly standard on all new machines.
The Production of High-Speed Helical Gears, with Special Reference to the Elimination of Transmission Noises
Authors: Couling S. A.
Published: October 2007

The paper records experience gained in the production of quiet-running high-speed helical gears. Sources of gear noise, and the early attempts at their elimination, are briefly stated, together with experiments of a similar nature with which the author has been associated. High-frequency noises, either due to the number of contacts per second or to the indexing wormwheel of the hobbing machine, are distinct from, and more irritating to the ear, than indeterminate noises due to rough running. Ear reaction to gear noise is dealt with, and a method of producing gears is given whereby the noise pulsations are made high enough to be less objectionable to the ear.

Hobbing machines with the indexing wormwheel and table solid are advocated, as opposed to machines having the “creep” mechanism. One firm's experience along these lines is given, together with a description of the method which they adopted to eliminate some causes of gear noise. Examples of sets in service, and of their tooth loads and noise levels, are given, as well as special analytical test figures.
Performance Estimation of Axial Flow Turbines
Authors: Craig H. R. M. , Cox H. J. A.
Published: October 2007

A comprehensive method of estimating the performance of axial flow steam and gas turbines is presented, based on analysis of linear cascade tests on blading, on a number of turbine test results, and on air tests of model casings. The validity of the use of such data is briefly considered. Data are presented to allow performance estimation of actual machines over a wide range of Reynolds number, Mach number, aspect ratio and other relevant variables. The use of the method in connection with three-dimensional methods of flow estimation is considered, and data presented showing encouraging agreement between estimates and available test results. Finally ‘carpets’ are presented showing the trends in efficiencies that are attainable in turbines designed over a wide range of loading, axial velocity/blade speed ratio, Reynolds number and aspect ratio.
A3B Intermetallics: Defect chemistry and nonstoichiometry
Authors: Ipser Herbert
Published: October 2007

The defect chemistry of different ordered intermetallic compounds with the A3B stoichiometry was investigated. Three groups were distinguished according to their crystal structure: L12 compounds (Ni3Al, Ni3Ga, Pt3Ga, Pt3In), D019 compounds (Ti3Al), and D03 compounds (Fe3Al, Ni3Sb). Statistical-thermodynamic models were derived based on a Wagner-Schottky approach, and the calculated activity curves (thermodynamic activity vs. composition) were compared with experimental activity data. In this way, we attempted to obtain at least estimated values for the energies of formation of the different types of point defects present in the corresponding compound, both as configurational defects (which are responsible for nonstoichiometry) and as thermal defects. In the majority of cases, thermodynamic activities had to be determined experimentally in the present study, using either an emf method with a solid electrolyte (Ni3Ga, Pt3Ga, Pt3In, Fe3Al) or a Knudsen cell-mass spectrometric method (Ni3Sb).
Representation of configuration in coordination polyhedra and the extension of current methodology to coordination numbers greater than six (IUPAC Technical Report)
Authors: Hartshorn Richard M. , Hey-Hawkins Evamarie , Kalio René , Leigh G. Jeffery
Published: October 2007

Established IUPAC recommendations for the representation of configuration are reviewed briefly, and then methodologies are examined for dealing with regular polyhedra that are typically used when working with coordination numbers greater than 6. More than one method is available and can be used for many such geometries, but the deviations from regular polyhedral geometries that are typically found in such molecules can make it difficult to arrive reproducibly at the same description for a complex using purely objective criteria. Recommendations are made for some geometries of coordination numbers 7, 8, and 9, but not for higher coordination numbers.
Definitions of terms relating to the structure and processing of sols, gels, networks, and inorganic-organic hybrid materials (IUPAC Recommendations 2007)
Authors: Alemán J. V. , Chadwick A. V. , He J. , Hess M. , Horie K. , Jones R. G. , Kratochvíl P. , Meisel I. , Mita I. , Moad G. , Penczek S. , Stepto R. F. T.
Published: October 2007

This document defines terms related to the structure and processing of inorganic, polymeric, and inorganic-organic hybrid materials from precursors, through gels to solid products. It is divided into four sections - precursors, gels, solids, and processes - and the terms have been restricted to those most commonly encountered. For the sake of completeness and where they are already satisfactorily defined for the scope of this document, terms from other IUPAC publications have been used. Otherwise, the terms and their definitions have been assembled in consultation with experts in the relevant fields. The definitions are intended to assist the reader who is unfamiliar with sol-gel processing, ceramization, and related technologies and materials, and to serve as a guide to the use of standard terminology by those researching in these areas.
Can Comparison of MZ- and DZ-Twin Concordance Rates be Used Invariably to Estimate Heritability?
Authors: Tishler Peter V. , Carey Vincent J.
Published: October 2007

Proponents of the validity of the classical MZ-DZ twin comparison model for calculating heritability claim that the environments influencing MZ and DZ twin individuals are essentially identical. This ‘equal environments assumption’ may or may not be universally true when applied to the analysis of subjective traits. We examined the validity of this assumption as applied to the propensity for smoking cigarettes, reasoning that equality of environments should lead to equal smoking prevalences in MZ and DZ twin individuals. We identified 8 twin populations with data on smoking. We compiled odds ratios (ORs) for ever smoking in MZ and DZ twin individuals in these 8 studies and overall, using a fixed-effects meta-analytic method based on the Mantel-Haenszel procedure. The prevalence of smoking was less in MZ twin individuals than in DZ twin individuals in 7 of 8 studies. The overall OR was 0.86 (95% confidence interval 0.84, 0.89). ORs were virtually unchanged when the analyses were stratified for gender and age, and no differences were found in relation to the location of the study, the date of the study or the birth years of the cohorts. For cigarette smoking, the environments of MZ and DZ twins may not be co-equal. For subjective traits, heritability estimates may be influenced by these unequal environmental factors that differentially affect their development and characteristics in MZ and DZ twins.
Why More Boys Than Girls With ADHD Receive Treatment: A Study of Dutch Twins
Authors: Derks Eske M. , Hudziak James J. , Boomsma Dorret I.
Published: October 2007

More boys than girls with attention deficit hyperactivity disorder (ADHD) receive treatment. One explanation for this bias may be that boys score higher on disruptive behavior scales than girls. Although this was supported by findings in clinical samples, recent studies in nonreferred samples showed that boys and girls with ADHD are similar with respect to their levels of disruptive behavior as reported by their mother. In this report, we investigate whether the difference in treatment rate is associated with higher teacher problem scores in boys with ADHD than in girls with ADHD. Data were obtained from mothers and teachers in a nonreferred sample of 283 boys and 291 girls with and without ADHD. Children were selected when they scored either low (controls) or high (probands) on attention problems. Mothers completed DSM-IV interviews, Child Behavior Checklists (CBCL) and the Conners Rating Scale (CRS). Teachers filled in the Teacher Report Form (TRF), and the CRS. Boys and girls with ADHD had similar levels of psychiatric illness and school impairment (such as being held back, special class placement and learning problems) by mother report. Mothers reported similar levels of aggression and attention problems in boys and girls with ADHD. In contrast, teachers consistently rated boys with ADHD as having higher scores on reports of attention problems and aggression than girls with ADHD. Gender differences vary across settings: boys and girls with ADHD are rated as behaving differently at school, but not at home. The higher level of teacher reported problem behavior at school may explain the high male–female ratio for ADHD in clinical settings. These findings have implications for the results of genetic studies that rely on referred samples, as these studies may give a distorted view of sex differences in the population.
The Lives of Others: Matthew H. Bernstein on an Emotive Surveillance Thriller Set in Communist East Germany
Authors: Bernstein Matthew H.
Published: October 2007

ABSTRACT This essay explores the film allusions, plot turns, hierarchies of knowledge, and most of all the multiple ironies that contribute to the extraordinary impact of Florian Henckel von Donnersmarck's surveillance thriller set in Communist East Germany.
“A New Wave of Spectators”: Contemporary Responses to Cleo from 5 to 7
Authors: Conway Kelley
Published: October 2007

ABSTRACT The ciné-club was central to French fi lm culture in the 1950s and 60s. Analysis of ciné-club programming, educational activities, and of questionnaires fi lled out at the premier of Agnès Varda's Cleo from 5 to 7 reveals that the ciné-club powerfully shaped viewers' tastes and viewing skills.
Injury to the Developing Cerebellum
Authors: Limperopoulos Catherine , du Plessis Adré J.
Published: October 2007

Advances in neuroimaging techniques for the in vivo study of brain development have expanded the understanding of normal and abnormal cerebellar development in the high-risk fetus and newborn. This, in turn, has provided new insights into the spectrum of structural and functional consequences of injury to the developing cerebellum. Specifically, hemorrhagic cerebellar lesions in preterm infants are associated with significant impairment of subsequent cerebellar growth as well as impaired growth of the contralateral cerebral hemisphere. Furthermore, preterm extrauterine life appears to inhibit cerebellar growth, even in the absence of obvious primary injury. Recent long-term outcome studies in preterm infants who had cerebellar injury suggest a distinct profile of pervasive neurodevelopmental deficits, with a high prevalence of cognitive-behavioral dysfunction. The structure-function relationships between early cerebellar injury and long-term outcome are a fertile area for future research.