bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progression in familial and nonfamilial MS
Authors: Koch Marcus , Uyttenboogaart Maarten , Heerings Marco , Heersema Dorothea , Mostert Jop , De Keyser Jacques 
Published: January 2008

Objective To investigate whether the timing of secondary or primary progression is different between patients with familial and nonfamilial multiple sclerosis (MS). Methods Information on the family history of 313 patients with MS was taken from our prospective hospital-based database. We used Kaplan—Meier analyses and Cox regression models to evaluate differences between familial and nonfamilial MS in several endpoint measures. We investigated the risk of developing secondary progression in all patients with a relapsing—remitting disease onset, the length of the relapsing—remitting phase and age at onset of progression in patients with secondary progressive MS and the age at disease onset in patients with primary progressive MS (PPMS). Results Among the primary progressive patients, those with familial MS had a significantly younger age at disease onset than patients with nonfamilial MS (mean 33.04 years versus mean 37.73 years in nonfamilial MS, P = 0.02). There were no significant differences between familial and nonfamilial MS patients in any other investigated measure. Conclusions Familial MS appears related to the time of disease onset in PPMS. Patients with familial PPMS may be an important patient group for future genetic research in MS. Multiple Sclerosis 2008; 14: 300—306. http://msj.sagepub.com
Multiple sclerosis on-screen: from disaster to coping
Authors: Karenberg Axel 
Published: January 2008

Background Fictional portrayals of multiple sclerosis (MS) in film and on television have remained largely unexamined to date. The aim of this review is consequently to catalog and analyse every available film with an MS motif. Method The author has identified relevant productions by means of international film databases and by handsearch. Each film is systematically evaluated along neurological and cinematic lines. Results Between 1941 and 2006 MS appeared as a theme in 23 films. Because screenplay writers often make use of medical knowledge, from a neurological perspective many films present a largely accurate picture of this disease's symptoms. The visual character of the medium and the effects of dramatic composition result in the prominence of certain symptoms. Ataxia, paralysis, blurred vision and fatigue are found in films with the same frequency as in epidemiological studies whereas sensory symptoms, eye movement disorders, incontinence and difficulties with sexual function were underrepresented. These films thematize the effects of MS on patients' self-image, the psychological adaptation process and their relations with proxy in a special way. Parallel with improvements in therapy and changing social attitudes toward the handicapped, these films have progressed from the earlier `disaster' to modern `coping' stories. Conclusion The often life-like portrayal of MS distinguishes these films from the stereotypic representation of other neurological diseases. Because representations of MS in popular media have an immediate effect on an audience of millions, they deserve greater attention from professional neurology. Multiple Sclerosis 2008; 14: 530—540. http://msj.sagepub.com
KSHV LANA inhibits TGF-β signaling through epigenetic silencing of the TGF-β type II receptor
Authors: Di Bartolo Daniel L. , Cannon Mark , Liu Yi-Fang , Renne Rolf , Chadburn Amy , Boshoff Chris , Cesarman Ethel 
Published: January 2008

AbstractSignaling through the transforming growth factor–β (TGF-β) pathway results in growth inhibition and induction of apoptosis in various cell types. We show that this pathway is blocked in Kaposi sarcoma herpesvirus (KSHV)–infected primary effusion lymphoma through down-regulation of the TGF-β type II receptor (TβRII) by epigenetic mechanisms. Our data also suggest that KSHV infection may result in lower expression of TβRII in Kaposi sarcoma and multicentric Castleman disease. KSHV-encoded LANA associates with the promoter of TβRII and leads to its methylation and to the deacetylation of proximal histones. Reestablishment of signaling through this pathway reduces viability of these cells, inferring that KSHV-mediated blockage of TGF-β signaling plays a role in the establishment and progression of KSHV-associated neoplasia. These data suggest a mechanism whereby KSHV evades both the antiproliferative effects of TGF-β signaling by silencing TβRII gene expression and immune recognition by suppressing TGF-β–responsive immune cells through the elevated secretion of TGF-β1.
HIF-1α regulates epithelial inflammation by cell autonomous NFκB activation and paracrine stromal remodeling
Authors: Scortegagna Marzia , Cataisson Christophe , Martin Rebecca J. , Hicklin Daniel J. , Schreiber Robert D. , Yuspa Stuart H. , Arbeit Jeffrey M. 
Published: January 2008

AbstractHypoxia inducible factor-1 (HIF-1) is a master regulatory transcription factor controlling multiple cell-autonomous and non–cell-autonomous processes, such as metabolism, angiogenesis, matrix invasion, and cancer metastasis. Here we used a new line of transgenic mice with constitutive gain of HIF-1 function in basal keratinocytes and demonstrated a signaling pathway from HIF-1 to nuclear factor κ B (NFκB) activation to enhanced epithelial chemokine and cytokine elaboration. This pathway was responsible for a phenotypically silent accumulation of stromal inflammatory cells and a marked inflammatory hypersensitivity to a single 12-O-tetradecanoylphorbol-13-acetate (TPA) challenge. HIF-1–induced NFκB activation was composed of 2 elements, IκB hyperphosphorylation and phosphorylation of Ser276 on p65, enhancing p65 nuclear localization and transcriptional activity, respectively. NFκB transcriptional targets macrophage inflammatory protein-2 (MIP-2/CXCL2/3), keratinocyte chemokine (KC/CXCL1), and tumor necrosis factor [alfa] (TNFα) were constitutively up-regulated and further increased after TPA challenge both in cultured keratinocytes and in transgenic mice. Whole animal KC, MIP-2, or TNFα immunodepletion each abrogated TPA-induced inflammation, whereas blockade of either VEGF or placenta growth factor (PlGF) signaling did not affect transgenic inflammatory hyper-responsiveness. Thus, epithelial HIF-1 gain of function remodels the local environment by cell-autonomous NFκB-mediated chemokine and cytokine secretion, which may be another mechanism by which HIF-1 facilitates either inflammatory diseases or malignant progression.
The effects of the surface-exposed residues on the binding and hydrolytic activities of Vibrio carchariae chitinase A
Authors: Pantoom Supansa , Songsiriritthigul Chomphunuch , Suginta Wipa 
Published: January 2008

Abstract

Background

Vibrio carchariae chitinase A (EC3.2.1.14) is a family-18 glycosyl hydrolase and comprises three distinct structural domains: i) the amino terminal chitin binding domain (ChBD); ii) the (α/β)8 TIM barrel catalytic domain (CatD); and iii) the α + β insertion domain. The predicted tertiary structure of V. carchariae chitinase A has located the residues Ser33 & Trp70 at the end of ChBD and Trp231 & Tyr245 at the exterior of the catalytic cleft. These residues are surface-exposed and presumably play an important role in chitin hydrolysis.

Results
Point mutations of the target residues of V. carchariae chitinase A were generated by site-directed mutagenesis. With respect to their binding activity towards crystalline α-chitin and colloidal chitin, chitin binding assays demonstrated a considerable decrease for mutants W70A and Y245W, and a notable increase for S33W and W231A. When the specific hydrolyzing activity was determined, mutant W231A displayed reduced hydrolytic activity, whilst Y245W showed enhanced activity. This suggested that an alteration in the hydrolytic activity was not correlated with a change in the ability of the enzyme to bind to chitin polymer. A mutation of Trp70 to Ala caused the most severe loss in both the binding and hydrolytic activities, which suggested that it is essential for crystalline chitin binding and hydrolysis. Mutations varied neither the specific hydrolyzing activity against p NP-[GlcNAc]2, nor the catalytic efficiency against chitohexaose, implying that the mutated residues are not important in oligosaccharide hydrolysis.

Conclusion
Our data provide direct evidence that the binding as well as hydrolytic activities of V. carchariae chitinase A to insoluble chitin are greatly influenced by Trp70 and less influenced by Ser33. Though Trp231 and Tyr245 are involved in chitin hydrolysis, they do not play a major role in the binding process of crystalline chitin and the guidance of the chitin chain into the substrate binding cleft of the enzyme.
Genetic loci linked to Type 1 Diabetes and Multiple Sclerosis families in Sardinia
Authors: Pitzalis Maristella , Zavattari Patrizia , Murru Raffaele , Deidda Elisabetta , Zoledziewska Magdalena , Murru Daniela , Moi Loredana , Motzo Costantino , Orrù Valeria , Costa Gianna , Solla Elisabetta , Fadda Elisabetta , Schirru Lucia , Melis Maria Cristina , Lai Marina , Mancosu Cristina , Tranquilli Stefania , Cuccu Stefania , Rolesu Marcella , Secci Maria Antonietta , Corongiu Daniela , Contu Daniela , Lampis Rosanna , Nucaro Annalisa , Pala Gavino , Pacifico Adolfo , Maioli Mario , Frongia Paola , Chessa Margherita , Ricciardi Rossella , Lostia Stanislao , Marinaro Anna Maria , Milia Anna Franca , Landis Novella , Zedda Maria Antonietta , Whalen Michael B , Santoni Federico , Marrosu Maria Giovanna , Devoto Marcella , Cucca Francesco 
Published: January 2008

Abstract

Background
The Mediterranean island of Sardinia has a strikingly high incidence of the autoimmune disorders Type 1 Diabetes (T1D) and Multiple Sclerosis (MS). Furthermore, the two diseases tend to be co-inherited in the same individuals and in the same families. These observations suggest that some unknown autoimmunity variant with relevant effect size could be fairly common in this founder population and could be detected using linkage analysis.

Methods
To search for T1D and MS loci as well as any that predispose to both diseases, we performed a whole genome linkage scan, sequentially genotyping 593 microsatellite marker loci in 954 individuals distributed in 175 Sardinian families. In total, 413 patients were studied; 285 with T1D, 116 with MS and 12 with both disorders. Model-free linkage analysis was performed on the genotyped samples using the Kong and Cox logarithm of odds (LOD) score statistic.

Results
In T1D, aside from the HLA locus, we found four regions showing a lod-score ≥1; 1p31.1, 6q26, 10q21.2 and 22q11.22. In MS we found three regions showing a lod-score ≥1; 1q42.2, 18p11.21 and 20p12.3. In the combined T1D-MS scan for shared autoimmunity loci, four regions showed a LOD >1, including 6q26, 10q21.2, 20p12.3 and 22q11.22. When we typed more markers in these intervals we obtained suggestive evidence of linkage in the T1D scan at 10q21.2 (LOD = 2.1), in the MS scan at 1q42.2 (LOD = 2.5) and at 18p11.22 (LOD = 2.6). When all T1D and MS families were analysed jointly we obtained suggestive evidence in two regions: at 10q21.1 (LOD score = 2.3) and at 20p12.3 (LOD score = 2.5).

Conclusion
This suggestive evidence of linkage with T1D, MS and both diseases indicates critical chromosome intervals to be followed up in downstream association studies.
Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts
Authors: Barrera David , Avila Euclides , Hernández Guillermo , Méndez Isabel , González Leticia , Halhali Ali , Larrea Fernando , Morales Angélica , Díaz Lorenza 
Published: January 2008

Abstract

Background
In pregnancy, maternal serum concentrations of calcitriol significantly rise as a result of increased renal and placental contribution in order to assure calcium supply for the developing fetus. Considering that placenta is a site for vitamin D activation, and the versatility and potency of calcitriol, it is feasible that this hormone participates in fetal/placental development and physiology. In the present work we studied calcitriol actions upon human chorionic gonadotropin (hCG) secretion and expression in cultured trophoblasts, as well as vitamin D receptor (VDR) and CYP27B1 immunolocalization in placental villi.

Methods
Quantification of hCG in culture media was performed by immunoassay. Expression studies were carried out by real time PCR. Analysis of CYP27B1 and VDR localization in placental slides were performed by immunohistochemistry. Statistical significance was established by one way ANOVA using Tukey test for comparisons.

Results
Calcitriol regulated hCG in a time-dependent manner: at 6 h the secosteroid stimulated hCG, whereas longer incubations (24 h) showed opposite effects. Interestingly, calcitriol stimulatory effects on hCG were accompanied by an increase in intracellular cAMP content and were abolished by pre-incubation of the cells with a selective protein kinase A inhibitor. Immunohistochemical techniques showed differential VDR localization in the syncytiotrophoblast layer or in the vascular smooth muscle cells depending on the epitope to which the antibodies were raised (specific for the carboxy- or amino-terminal regions, respectively). CYP27B1 was immunolocalized in the syncytiotrophoblast layer of placental villi.

Conclusion
The presence and location of the vitamin D activating enzyme CYP27B1 as well as the specific receptor for vitamin D were shown in placental sections. The latter, together with findings demonstrating specific effects of calcitriol acting through the VDR and the cAMP/PKA signaling pathway upon hCG expression and secretion, indicate that there is a functional vitamin D endocrine system in the placenta, and recognize calcitriol as an autocrine regulator of hCG.
Tobacco industry issues management organizations: Creating a global corporate network to undermine public health
Authors: McDaniel Patricia A , Intinarelli Gina , Malone Ruth E 
Published: January 2008

AbstractBackgroundThe global tobacco epidemic claims 5 million lives each year, facilitated by the ability of transnational tobacco companies to delay or thwart meaningful tobacco control worldwide. A series of cross-company tobacco industry "issues management organizations" has played an important role in coordinating and implementing common strategies to defeat tobacco control efforts at international, national, and regional levels. This study examines the development and enumerates the activities of these organizations and explores the implications of continuing industry cooperation for global public health.MethodsUsing a snowball sampling strategy, we collected documentary data from tobacco industry documents archives and assembled them into a chronologically organized case study.ResultsThe International Committee on Smoking Issues (ICOSI) was formed in 1977 by seven tobacco company chief executives to create common anti-tobacco control strategies and build a global network of regional and national manufacturing associations. The organization's name subsequently changed to INFOTAB. The multinational companies built the organization rapidly: by 1984, it had 69 members operating in 57 countries. INFOTAB material, including position papers and "action kits" helped members challenge local tobacco control measures and maintain tobacco-friendly environments. In 1992 INFOTAB was replaced by two smaller organizations. The Tobacco Documentation Centre, which continues to operate, distributes smoking-related information and industry argumentation to members, some produced by cross-company committees. Agro-Tobacco Services, and now Hallmark Marketing Services, assists the INFOTAB-backed and industry supported International Tobacco Growers Association in advancing claims regarding the economic importance of tobacco in developing nations.ConclusionThe massive scale and scope of this industry effort illustrate how corporate interests, when threatened by the globalization of public health, sidestep competitive concerns to coordinate their activities. The global network of national and regional manufacturing associations created and nurtured by INFOTAB remains active, particularly in relation to the recently negotiated global health treaty, the Framework Convention on Tobacco Control. Policymakers should be aware that although these associations claim to represent only national or regional interests, they are allied to and coordinated with a confederation of transnational tobacco companies seeking to protect profits by undermining public health.
Derlin-1 is overexpressed in human breast carcinoma and protects cancer cells from endoplasmic reticulum stress-induced apoptosis
Authors: Wang Jiao , Hua Hui , Ran Yuliang , Zhang Hongyin , Liu Weiping , Yang Zhihua , Jiang Yangfu 
Published: January 2008

Abstract
Introduction
Aberrant microenvironment and endoplasmic reticulum (ER) stress are associated with solid-tumor progression. Stress proteins, like heat shock proteins and glucose-regulated proteins, are frequently overexpressed in human tumors. It has been reported that derlin-1 is involved in ER stress response. In vitro studies have demonstrated that derlin-1 participates in the retrotranslocation of misfolded proteins from ER into the cytosol. Because the roles of derlin-1 in human cancer have not yet been characterized, we investigated the expression of derlin-1 in human breast carcinoma and whether it protected cancer cells against ER stress-induced apoptosis.

Methods
Surgical specimens of human breast cancer and/or paired normal tissues from the same patients were collected for immunohistochemical and/or Western blot analysis with anti-human derlin-1 antibody. The expression of derlin-1 in human breast cancer cell lines was detected by reverse transcription-polymerase chain reaction or Western blot. A synthetic small interfering RNA against derlin-1 was introduced into breast cancer cells to inhibit derlin-1 expression. The effects of derlin-1 knockdown on ER stress-induced apoptosis were determined by flow cytometry analysis.

Results
These analyses demonstrated that 66.7% of the breast carcinoma tissues expressed derlin-1, whereas derlin-1 was rarely expressed in normal mammary glands. The expression of derlin-1 in human breast carcinoma correlated with tumor grade and axillary lymph node metastasis. On examining the expression of derlin-1 in human breast cancer cell lines, we found that derlin-1 expression was enhanced by ER stress-inducing agents. Derlin-1 knockdown sensitized breast cancer cells to ER stress-induced apoptosis.

Conclusion
The observed derlin-1 overexpression in breast cancer, together with its function in relieving ER stress-induced apoptosis, suggests that regulation of the ER stress response pathway may be critical in the development and progression of breast cancer.
Biphasic onset of splenic apoptosis following hemorrhagic shock: critical implications for Bax, Bcl-2, and Mcl-1 proteins
Authors: Hostmann Arwed , Jasse Kerstin , Schulze-Tanzil Gundula , Robinson Yohan , Oberholzer Andreas , Ertel Wolfgang , Tschoeke Sven K 
Published: January 2008

Abstract
Introduction
The innate immune response to trauma hemorrhage involves inflammatory mediators, thus promoting cellular dysfunction as well as cell death in diverse tissues. These effects ultimately bear the risk of post-traumatic complications such as organ dysfunction, multiple organ failure, or adult respiratory distress syndrome. In this study, a murine model of resuscitated hemorrhagic shock (HS) was used to determine the apoptosis in spleen as a marker of cellular injury and reduced immune functions.

Methods
Male C57BL-6 mice were subjected to sham operation or resuscitated HS. At t = 0 hours, t = 24 hours, and t = 72 hours, mice were euthanized and the spleens were removed and evaluated for apoptotic changes via DNA fragmentation, caspase activities, and activation of both extrinsic and intrinsic apoptotic pathways. Spleens from untreated mice were used as control samples.

Results
HS was associated with distinct lymphocytopenia as early as t = 0 hours after hemorrhage without regaining baseline levels within the consecutive 72 hours when compared with sham and control groups. A rapid activation of splenic apoptosis in HS mice was observed at t = 0 hours and t = 72 hours after hemorrhage and predominantly confirmed by increased DNA fragmentation, elevated caspase-3/7, caspase-8, and caspase-9 activities, and enhanced expression of intrinsic mitochondrial proteins. Accordingly, mitochondrial pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were inversely expressed within the 72-hour observation period, thereby supporting significant pro-apoptotic changes. Solely at t = 24 hours, expression of the anti-apoptotic Mcl-1 protein shows a significant increase when compared with sham-operated and control animals. Furthermore, expression of extrinsic death receptors were only slightly increased.

Conclusion
Our data suggest that HS induces apoptotic changes in spleen through a biphasic caspase-dependent mechanism and imply a detrimental imbalance of pro- and anti-apoptotic mitochondrial proteins Bax, Bcl-2, and Mcl-1, thereby promoting post-traumatic immunosuppression.
Exploring systemic RNA interference in insects: a genome-wide survey for RNAi genes in Tribolium
Authors: Tomoyasu Yoshinori , Miller Sherry C , Tomita Shuichiro , Schoppmeier Michael , Grossmann Daniela , Bucher Gregor 
Published: January 2008

Abstract
Background
RNA interference (RNAi) is a highly conserved cellular mechanism. In some organisms, such as Caenorhabditis elegans, the RNAi response can be transmitted systemically. Some insects also exhibit a systemic RNAi response. However, Drosophila, the leading insect model organism, does not show a robust systemic RNAi response, necessitating another model system to study the molecular mechanism of systemic RNAi in insects.

Results
We used Tribolium, which exhibits robust systemic RNAi, as an alternative model system. We have identified the core RNAi genes, as well as genes potentially involved in systemic RNAi, from the Tribolium genome. Both phylogenetic and functional analyses suggest that Tribolium has a somewhat larger inventory of core component genes than Drosophila, perhaps allowing a more sensitive response to double-stranded RNA (dsRNA). We also identified three Tribolium homologs of C. elegans sid-1, which encodes a possible dsRNA channel. However, detailed sequence analysis has revealed that these Tribolium homologs share more identity with another C. elegans gene, tag-130. We analyzed tag-130 mutants, and found that this gene does not have a function in systemic RNAi in C. elegans. Likewise, the Tribolium sid-like genes do not seem to be required for systemic RNAi. These results suggest that insect sid-1-like genes have a different function than dsRNA uptake. Moreover, Tribolium lacks homologs of several genes important for RNAi in C. elegans.

Conclusion
Although both Tribolium and C. elegans show a robust systemic RNAi response, our genome-wide survey reveals significant differences between the RNAi mechanisms of these organisms. Thus, insects may use an alternative mechanism for the systemic RNAi response. Understanding this process would assist with rendering other insects amenable to systemic RNAi, and may influence pest control approaches.