bluuebunny/crossref_metadata_2025 huggingface dataset:
Small Molecule Targeting the Hec1/Nek2 Mitotic Pathway Suppresses Tumor Cell Growth in Culture and in Animal
Authors: Wu Guikai , Qiu Xiao-Long , Zhou Longen , Zhu Jiewen , Chamberlin Richard , Lau Johnson , Chen Phang-Lang , Lee Wen-Hwa
Published: October 2008

Hec1 is a conserved mitotic regulator critical for spindle checkpoint control, kinetochore functionality, and cell survival. Overexpression of Hec1 has been detected in a variety of human cancers and is linked to poor prognosis of primary breast cancers. Through a chemical genetic screening, we have identified a small molecule, N-(4-[2,4-dimethyl-phenyl]-thiazol-2-yl)-benzamide (INH1), which specifically disrupts the Hec1/Nek2 interaction via direct Hec1 binding. Treating cells with INH1 triggered reduction of kinetochore-bound Hec1 as well as global Nek2 protein level, consequently leading to metaphase chromosome misalignment, spindle aberrancy, and eventual cell death. INH1 effectively inhibited the proliferation of multiple human breast cancer cell lines in culture (GI50, 10–21 μmol/L). Furthermore, treatment with INH1 retarded tumor growth in a nude mouse model bearing xenografts derived from the human breast cancer line MDA-MB-468, with no apparent side effects. This study suggests that the Hec1/Nek2 pathway may serve as a novel mitotic target for cancer intervention by small compounds. [Cancer Res 2008;68(20):8393–9]
The Thioredoxin System Mediates Redox-Induced Cell Death in Human Colon Cancer Cells: Implications for the Mechanism of Action of Anticancer Agents
Authors: Sun Yu , Rigas Basil
Published: October 2008

Anticancer agents act, at least in part, by inducing reactive oxygen and nitrogen species (RONS). We examined the redox effect on SW480 and HT-29 colon cancer cells of four anticancer compounds, arsenic trioxide, phosphoaspirin, phosphosulindac, and nitric oxide–donating aspirin (NO-ASA). All compounds inhibited the growth of both cell lines (IC50, 10–90 μmol/L) and induced RONS detected by a general RONS molecular probe. NO-ASA, which induced at least four individual RONS (NO, H2O2, superoxide anion, and peroxynitirte), induced apoptotic and necrotic cell death that was RONS-mediated (cell death paralleled RONS levels and was abrogated by N-acetyl cysteine but not by diphenylene iodonium, which displayed prooxidant activity and enhanced cell death). Nuclear factor-κB and mitogen-activated protein kinases were modulated by RONS. Thioredoxin-1 (Trx-1), an oxidoreductase involved in redox regulation, was heavily oxidized in response to RONS and mediated the growth inhibitory effect of the anticancer agents; knocking-down trx-1 expression by small interfering RNA abrogated cell death induced by them. These compounds also inhibited the activity of Trx reductase that reduces oxidized Trx-1, whereas the Trx reductase inhibitor aurothiomalate synergized with NO-ASA in the induction of cell death. Our findings indicate that the Trx system mediates to a large extent redox-induced cell death in response to anticancer agents. This mechanism of action may be shared by more anticancer agents and deserves further assessment as a candidate mechanism for the pharmacologic control of cancer. [Cancer Res 2008;68(20):8269–77]
Roles of Idiotype-Specific T Cells in Myeloma Cell Growth and Survival: Th1 and CTL Cells Are Tumoricidal while Th2 Cells Promote Tumor Growth
Authors: Hong Sungyoul , Qian Jianfei , Yang Jing , Li Haiyan , Kwak Larry W. , Yi Qing
Published: October 2008

Idiotype (Id) protein, secreted by myeloma cells, is a tumor-specific antigen. Id-based immunotherapy has been explored in patients with myeloma, and results were disappointing. Although previous studies have shown that Id-specific CTLs are able to lyse myeloma cells, it is unclear whether other types of Id-specific T cells, such as type-1 T-helper (Th1) and type-2 T-helper (Th2) cells, are also able to suppress or kill myeloma cells. Using a 5T murine myeloma model, we generated T-cell clones of different subsets and examined their function in the context of myeloma cells. Id-specific CTLs specifically lysed myeloma cells via MHC class I, perforin, and Fas ligand (FasL), and Th1, but not Th2, cells lysed the myeloma cells by FasL–Fas interaction. CTL and Th1 cells also suppressed the growth and function of myeloma cells, whereas Th2 cells promoted the proliferation and enhanced the secretion of Id protein and cytokines by myeloma cells. CTL and Th1, but not Th2, cells were able to eradicate established myeloma in vivo after adoptive transfer. These results show that Id-specific CTL and Th1 are promising effector cells, whereas Th2 provide no protection and may even promote tumor progression in vivo. [Cancer Res 2008;68(20):8456–64]
A Dietary Anthocyanidin Delphinidin Induces Apoptosis of Human Prostate Cancer PC3 Cells In vitro and In vivo: Involvement of Nuclear Factor-κB Signaling
Authors: Hafeez Bilal Bin , Siddiqui Imtiaz Ahmad , Asim Mohammad , Malik Arshi , Afaq Farrukh , Adhami Vaqar Mustafa , Saleem Mohammad , Din Maria , Mukhtar Hasan
Published: October 2008

Delphinidin, a major anthocyanidin present in many pigmented fruits and vegetables, possesses antioxidant, anti-inflammatory, and antiangiogenic properties. In this study, we provide evidence that it could be developed as a novel agent against human prostate cancer (PCa). We observed that delphinidin treatment to human PCa LNCaP, C4-2, 22Rν1, and PC3 cells resulted in a dose-dependent inhibition of cell growth without having any substantial effect on normal human prostate epithelial cells. We selected PC3 cells as a test model system because of their highly aggressive proliferative nature. Delphinidin treatment of cells resulted in a dose-dependent induction of apoptosis and arrest of cells in G2-M phase. This induction of apoptosis seems to be mediated via activation of caspases because N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluromethylketone significantly reduced apoptosis induced by delphinidin. We also observed that delphinidin treatment of cells resulted in a dose-dependent decrease in (a) phosphorylation of IκB kinase γ (NEMO), (b) phosphorylation of nuclear factor-κB (NF-κB) inhibitory protein IκBα, (c) phosphorylation of NF-κB/p65 at Ser536 and NF-κB/p50 at Ser529, (d) NF-κB/p65 nuclear translocation, and (e) NF-κB DNA binding activity. Delphinidin administration (2 mg, i.p. thrice weekly) to athymic nude mice implanted with PC3 cells resulted in a significant inhibition of tumor growth. Analysis of tumors from delphinidin-treated mice showed significant decrease in the expression of NF-κB/p65, Bcl2, Ki67, and PCNA. Taken together, our data suggest that delphinidin could be developed as an agent against human PCa. [Cancer Res 2008;68(20):8564–72]
Toll-Like Receptor 9 Mediates CpG Oligonucleotide–Induced Cellular Invasion
Authors: Ilvesaro Joanna M. , Merrell Melinda A. , Li Li , Wakchoure Savita , Graves David , Brooks Sonja , Rahko Eeva , Jukkola-Vuorinen Arja , Vuopala Katri S. , Harris Kevin W. , Selander Katri S.
Published: October 2008

Toll-like receptor 9 (TLR9) belongs to the innate immune system and recognizes microbial and vertebrate DNA. We showed previously that treatment with the TLR9-agonistic ODN M362 (a CpG sequence containing oligonucleotide) induces matrix metalloproteinase-13–mediated invasion in TLR9-expressing human cancer cell lines. Here, we further characterized the role of the TLR9 pathway in this process. We show that CpG oligonucleotides induce invasion in macrophages from wild-type C57/B6 and MyD88 knockout mice and in human MDA-MB-231 breast cancer cells lacking MyD88 expression. This effect was significantly inhibited in macrophages from TLR9 knockout mice and in human MDA-MB-231 breast cancer cells stably expressing TLR9 small interfering RNA or dominant-negative tumor necrosis factor receptor-associated factor 6 (TRAF6). Sequence modifications to the CpG oligonucleotides that targeted the stem loop and other secondary structures were shown to influence the invasion-inducing effect in MDA-MB-231 cells. In contrast, methylation of the cytosine residues of the parent CpG oligonucleotide did not affect the TLR9-mediated invasion compared with the unmethylated parent CpG oligonucleotide. Finally, expression of TLR9 was studied in clinical breast cancer samples and normal breast epithelium with immunohistochemistry. TLR9 staining localized in epithelial cells in both cancer and normal samples. The mean TLR9 staining intensity was significantly increased in the breast cancer cells compared with normal breast epithelial cells. In conclusion, our results suggest that TLR9 expression is increased in breast cancer and CpG oligonucleotide–induced cellular invasion is mediated via TLR9 and TRAF6, independent of MyD88. Further, our findings suggest that the structure and/or stability of DNA may influence the induction of TLR9-mediated invasion in breast cancer. (Mol Cancer Res 2008;6(10):1534–43)
Induction of Antiproliferative Connective Tissue Growth Factor Expression in Wilms' Tumor Cells by Sphingosine-1-Phosphate Receptor 2
Authors: Li Mei-Hong , Sanchez Teresa , Pappalardo Anna , Lynch Kevin R. , Hla Timothy , Ferrer Fernando
Published: October 2008

Connective tissue growth factor (CTGF), a member of the CCN family of secreted matricellular proteins, regulates fibrosis, angiogenesis, cell proliferation, apoptosis, tumor growth, and metastasis. However, the role of CTGF and its regulation mechanism in Wilms' tumor remains largely unknown. We found that the bioactive lipid sphingosine-1-phosphate (S1P) induced CTGF expression in a concentration- and time-dependent manner in a Wilms' tumor cell line (WiT49), whereas FTY720-phosphate, an S1P analogue that binds all S1P receptors except S1P2, did not. Further, the specific S1P2 antagonist JTE-013 completely inhibited S1P-induced CTGF expression, whereas the S1P1 antagonist VPC44116 did not, indicating that this effect was mediated by S1P2. This was confirmed by adenoviral transduction of S1P2 in WiT49 cells, which showed that overexpression of S1P2 increased the expression of CTGF. Induction of CTGF by S1P was sensitive to ROCK inhibitor Y-27632 and c-Jun NH2-terminal kinase inhibitor SP600125, suggesting the requirement of RhoA/ROCK and c-Jun NH2-terminal kinase pathways for S1P-induced CTGF expression. Interestingly, the expression levels of CTGF were decreased in 8 of 10 Wilms' tumor tissues compared with matched normal tissues by quantitative real-time PCR and Western blot analysis. In vitro, human recombinant CTGF significantly inhibited the proliferation of WiT49 cells. In addition, overexpression of CTGF resulted in significant inhibition of WiT49 cell growth. Taken together, these data suggest that CTGF protein induced by S1P2 might act as a growth inhibitor in Wilms' tumor. (Mol Cancer Res 2008;6(10):1649–56)
Angiogenic Factor Thymidine Phosphorylase Increases Cancer Cell Invasion Activity in Patients with Gastric Adenocarcinoma
Authors: Yu Eun Jeong , Lee Young , Rha Sun Young , Kim Tae Soo , Chung Hyun Cheol , Oh Bong Kyeong , Yang Woo Ick , Noh Sung Hoon , Jeung Hei-Cheul
Published: October 2008

We investigated the biological role of thymidine phosphorylase (TP), an angiogenic factor, in gastric cancer cell migration and invasion and explored a therapeutic approach for high TP-expressing tumors using TP enzymatic inhibitor (TPI) and rapamycin. We established TP cDNA overexpressing gastric cancer cell lines (MKN-45/TP and YCC-3/TP) and did invasion and adhesion assays with Matrigel-coated transwell membranes. The related signal pathway using recombinant human TP (rhTP), deoxy-d-ribose (D-dRib), and signal pathway inhibitors (wortmannin, LY294002, and rapamycin) was investigated. First, AGS and MKN-1 gastric cancer cell lines showed dose-dependent up-regulation of invasiveness through Matrigel following treatment with rhTP or D-dRib. TP-overexpressing cancer cell lines displayed increased migration and invasion activity, which doubled with rhTP and D-dRib treatment. This activity depended on the enzymatic activity of TP, and TP stimulated the adhesion of cancer cells onto Matrigel and induced actin filament remodeling. Finally, we showed that this activity is related to increased phosphatidylinositol 3-kinase activity in TP-overexpressing cells and that combination treatment with rapamycin and TP enzymatic inhibitor produces an additive effect to abrogate TP-induced invasion. Taken together, TP increases the migration and invasion of gastric cancer cells, especially in TP-expressing cells. Therapies targeting TP might diminish the propensity for invasion and metastasis in gastric cancer. (Mol Cancer Res 2008;6(10):1554–66)
Potentiation of Temozolomide Cytotoxicity by Poly(ADP)Ribose Polymerase Inhibitor ABT-888 Requires a Conversion of Single-Stranded DNA Damages to Double-Stranded DNA Breaks
Authors: Liu Xuesong , Shi Yan , Guan Ran , Donawho Cherrie , Luo Yanping , Palma Joann , Zhu Gui-dong , Johnson Eric F. , Rodriguez Luis E. , Ghoreishi-Haack Nayereh , Jarvis Ken , Hradil Vincent P. , Colon-Lopez Milagros , Cox Bryan F. , Klinghofer Vered , Penning Thomas , Rosenberg Saul H. , Frost David , Giranda Vincent L. , Luo Yan
Published: October 2008

Poly(ADP-ribose) polymerase (PARP) senses DNA breaks and facilitates DNA repair via the polyADP-ribosylation of various DNA binding and repair proteins. We explored the mechanism of potentiation of temozolomide cytotoxicity by the PARP inhibitor ABT-888. We showed that cells treated with temozolomide need to be exposed to ABT-888 for at least 17 to 24 hours to achieve maximal cytotoxicity. The extent of cytotoxicity correlates with the level of double-stranded DNA breaks as indicated by γH2AX levels. In synchronized cells, damaging DNA with temozolomide in the presence of ABT-888 during the S phase generated high levels of double-stranded breaks, presumably because the single-stranded DNA breaks resulting from the cleavage of the methylated nucleotides were converted into double-stranded breaks through DNA replication. As a result, treatment of temozolomide and ABT-888 during the S phase leads to higher levels of cytotoxicity. ABT-888 inhibits poly(ADP-ribose) formation in vivo and enhances tumor growth inhibition by temozolomide in multiple models. ABT-888 is well tolerated in animal models. ABT-888 is currently in clinical trials in combination with temozolomide. (Mol Cancer Res 2008;6(10):1621–9)
RhoA Silencing Reverts the Resistance to Doxorubicin in Human Colon Cancer Cells
Authors: Doublier Sophie , Riganti Chiara , Voena Claudia , Costamagna Costanzo , Aldieri Elisabetta , Pescarmona Gianpiero , Ghigo Dario , Bosia Amalia
Published: October 2008

The efficacy of doxorubicin in the treatment of cancer is limited by its side effects and by the onset of drug resistance. Reverting such resistance could allow the decrease of the dose necessary to eradicate the tumor, thus diminishing the toxicity of the drug. We transfected doxorubicin-sensitive (HT29) and doxorubicin-resistant (HT29-dx) human colon cancer cells with RhoA small interfering RNA. The subsequent decrease of RhoA protein was associated with the increased sensitivity to doxorubicin in HT29 cells and the complete reversion of doxorubicin resistance in HT29-dx cells. RhoA silencing increased the activation of the nuclear factor-κB pathway, inducing the transcription and the activity of nitric oxide synthase. This led to the tyrosine nitration of the multidrug resistance protein 3 transporter (MRP3) and contributed to a reduced doxorubicin efflux. Moreover, RhoA silencing decreased the ATPase activity of P-glycoprotein (Pgp) in HT29 and HT29-dx cells as a consequence of the reduced expression of Pgp. RhoA silencing, by acting as an upstream controller of both MRP3 nitration and Pgp expression, was effective to revert the toxicity and accumulation of doxorubicin in both HT29 and HT29-dx cells. Therefore, we suggest that inactivating RhoA has potential clinical applications and might in the future become part of a gene therapy protocol. (Mol Cancer Res 2008;6(10):1607–20)
Phylogenetic position of the saola (Pseudoryx nghetinhensis) inferred from cytogenetic analysis of eleven species of Bovidae
Authors: Nguyen T.T. , Aniskin V.M. , Gerbault-Seureau M. , Planton H. , Renard J.P. , Nguyen B.X. , Hassanin A. , Volobouev V.T.
Published: October 2008

Previous morphological and molecular analyses failed to resolve the phylogenetic position of the critically endangered saola (Pseudoryx nghetinhensis) with respect to its placement in Bovina (cattle, bison, and yak) or Bubalina (Asian and African buffaloes). In the present study, G- and C-banding, Ag-staining and FISH with 28S and telomeric probes was undertaken for 17 bovid species. An analysis of these data allowed us to identify 49 structural rearrangements that included autosomes, gonosomes and 17 different NOR sites. The combined data set was subjected to a cladistic analysis aimed at: (i) providing new insights on phylogenetic relationships of the saola and other species within the subfamily Bovinae, and (ii) testing the suitability of different classes of chromosomal characters for phylogenetic reconstruction of the family Bovidae. The study revealed that nucleolar organizing regions (NORs) are phylogenetically informative. It was shown that at least one, or sometimes two of these characters punctuate divergences that include nodes that are the most basal in the tree, to those that are the most recent. In this context, the shared presence of three NORs in saola and species of Syncerus and Bubalus strongly suggests the saola’s placement within the subtribe Bubalina. This contrasts with Robertsonian rearrangements which are informative only at the generic level. These findings suggest that NORs are an important and frequently overlooked source of additional phylogenetic information within the Bovidae that may also have applicability at higher taxonomic levels, possibly even for Pecora.
Distribution patterns of phosphorylated Thr 3 and Thr 32 of histone H3 in plant mitosis and meiosis
Authors: Caperta A.D. , Rosa M. , Delgado M. , Karimi R. , Demidov D. , Viegas W. , Houben A.
Published: October 2008

Cell cycle dependent phosphorylation of conserved N-terminal tail residues of histone H3 has been described in both animal and plant cells. Through cytogenetic approaches using different plant species we show a detailed description of distribution patterns of phosphorylated histone H3 at either threonine 3 or threonine 32 in mitosis and meiosis. In meristematic cells of the large genome species Secale cereale, Vicia faba and Hordeum vulgare we have found that phosphorylation of both threonine residues begins in prophase, and dephosphorylation occurs in late anaphase. However, in the small genome species Arabidopsis thaliana dephosphorylation occurs at anaphase. In the first division of meiosis of species with large genomes phosphorylation of histone H3 at either threonine 3 or threonine 32 is seen first in diakinesis and extends to anaphase I, whereas in the second division these post-translational modifications are visible at metaphase II through anaphase II. While in A. thaliana dephosphorylation takes place at anaphase I and II. In all species analysed phosphorylated H3 at either threonine 3 or threonine 32 are distributed along the entire length of chromosomes during mitotic metaphase and metaphase I. In the second meiotic division threonine 3 phosphorylation is restricted to the pericentromeric domain, while phosphorylation of threonine 32 is widespread along chromosome arms of all species analysed.
Distribution of the tandem repeat sequences and karyotyping in cucumber (Cucumis sativus L.) by fluorescence in situ hybridization
Authors: Han Y.H. , Zhang Z.H. , Liu J.H. , Lu J.Y. , Huang S.W. , Jin W.W.
Published: October 2008

We analyzed repeat sequences composition in the genome of cucumber inbred line 9930 using whole-genome shotgun reads. The analysis showed that satellite DNA sequences are the most dominant components in the cucumber genome. The distribution pattern of several tandem repeat sequences (Type I/II, Type III and Type IV) on cucumber chromosomes was visualized using fluorescence in situ hybridization (FISH). The FISH signals of the Type III and 45S rDNA provide useful cytogenetic markers, whose position and fluorescence intensity allow for easy identification of all somatic metaphase chromosomes. A karyotype showing the position and fluorescence intensity of several tandem repeat sequences is constructed. The establishment of this FISH-based karyotype has created the basis for the integration of molecular, genetic and cytogenetic maps in Cucumis sativus and for the ultimate genome sequencing project as well.
Role of Vestibular Input in Triggering and Modulating Postural Responses in Unilateral and Bilateral Vestibular Loss Patients
Authors: Mbongo F. , Qu’hen C. , Vidal P.P. , Tran Ba Huy P. , de Waele C.
Published: October 2008

The aim of this study was to determine whether the greater medial-lateral (ML) instability observed in patients with compensated unilateral vestibular loss (UVL), tested on a seesaw platform with eyes closed, is task-dependent. UVL patients, categorized into three groups according to time since lesion (1 week, 1 month and 1 year), bilateral vestibular loss patients and age-matched healthy control subjects were tested in three dynamic postural tasks. These tasks involved different supports – a seesaw platform (Satel), a platform generating horizontal linear translations (Synapsys) and foam rubber placed on a static platform – each requiring different somatosensory cues to maintain equilibrium. Displacements of the subjects’ center of pressure in both the anterior-posterior (AP) and ML directions were recorded by strain gauges within the platforms. Only tests performed with eyes closed were analyzed. Bilateral vestibular loss patients fell during foam and seesaw trials but not on the platform generating translations. We previously reported that UVL patients had greater postural oscillations on the seesaw platform in the ML compared to AP direction. In this study, we show similar ML/AP differences in patient performance on foam when standing with ‘feet close together’. In contrast, these differences were not found when patients were tested on linear translation or on foam standing with feet apart. In conclusion, the postural performance of patients with vestibular loss depends on the exact task used to measure postural stability. UVL patients are less stable when subjected to movement in the ML direction because of the biomechanical constraints of the tasks and/or the availability of proprioceptive information.
Interaction between Angiotensin II, Osteoprotegerin, and Peroxisome Proliferator-Activated Receptor-γ in Abdominal Aortic Aneurysm
Authors: Moran Corey S. , Cullen Bradford , Campbell Julie H. , Golledge Jonathan
Published: October 2008

Background and Aims: Osteoprotegerin (OPG) has been associated with abdominal aortic aneurysm (AAA) expansion. Angiotensin II (AngII) receptor blockade has been shown to reduce OPG expression in human AAA tissue. Interaction between vascular AngII and OPG was further examined using cell culture and the AngII-infused ApoE–/– mouse AAA model. The ability of peroxisome proliferator-activated receptor-γ (PPARγ) activation to target OPG as potential therapy for AAA was also investigated. Methods and Results: Human aortic smooth muscle cells (AoSMC) exposed to AngII exhibited dose-dependent increase in the production OPG. A 3-fold increase in suprarenal aortic concentration of OPG was observed in AngII-infused ApoE–/– mice. AngII type 1 receptor expression in human AAA tissue, and AoSMC in vitro, was stimulated up 4-fold in the presence of OPG. This effect in AoSMC was counteracted in the presence of the PPARγ ligand, pioglitazone. Addition of PPARγ ligand to cultured human AAA explant reduced OPG secretion by 60% and tissue concentration of OPG and metalloproteinase 9 by 2- and 3-fold, respectively. Administration of pioglitazone to AngII-infused ApoE–/– mice significantly reduced aortic concentrations of OPG and metalloproteinase 9. Conclusions: These data support an interaction between AngII and OPG in aneurysm formation. Activation of PPARγ may have a role in treatment of AAA.
Effects of Erosive, Cariogenic or Combined Erosive/Cariogenic Challenges on Human Enamel
Authors: Honório H.M. , Rios D. , Santos C.F. , Magalhães A.C. , Buzalaf M.A.R. , Machado M.A.A.M.
Published: October 2008

Individuals with cariogenic diet can also consume erosive beverages. Thus, it seems necessary to investigate a possible caries/erosion interaction. To test in situ/ex vivo a combination of these challenges, 11 subjects wore intraoral appliances containing four enamel blocks randomly assigned. In the first 2-week phase, the appliances were immersed in a cola drink 3 times/day. Two blocks were free of plaque (erosion only: EO) and two blocks were covered with plaque (erosion + plaque: EP). In the second 2-week phase, four new blocks were all covered with plaque and subjected to a sucrose solution 8 times/day. Among the four new blocks, two were also subjected to the cola drink 3 times/day (erosion + caries: EC) while the other two were not (caries only: CO). Thus, in EO, the specimens were fixed at the intraoral appliance level. In EP, EC and CO they were fixed 1.0 mm under the appliance level and covered with plastic meshes for dental plaque accumulation. Changes in wear and hardness were measured. Data were tested using ANOVA and Tukey’s test (p < 0.05). Mean values of wear (µm) and change in hardness (kp/mm2) were: EO 4.82/310; EP 0.14/48; EC 0.34/245; CO 0.42/309. With respect to surface softening, EP and EC differed significantly from each other and from EO and CO, which did not differ significantly. EO presented significantly higher wear than the other groups. The data suggest that the presence of dental plaque can decrease the acid attack of an erosive drink and the association of erosive and cariogenic challenges showed less enamel alterations when compared to erosive or cariogenic challenges only.
Otologic Manifestations in Samter’s Syndrome
Authors: Caversaccio Marco , Häusler Rudolf , Helbling Arthur
Published: October 2008

Objective: It was the aim of this study to investigate the prevalence of otologic manifestations in a cohort of Samter’s syndrome patients (nasal polyps with chronic rhinosinusitis, aspirin intolerance and asthma). Methods: We analyzed a retrospective and prospective case review from 1995 to 2005, performed in the otorhinolaryngology outpatient clinic of a tertiary referral center. Ear history, clinical examinations, treatment and outcome were evaluated using office and hospital records in 23 cases. All subjects completed a questionnaire. Results: In 6 cases (26%), otological manifestations with ear pressure and conductive hearing loss occurred during an advanced stage of Samter’s syndrome (>5 years after onset of the first nasal symptoms) partially responsive to systemic steroids. Conclusion: Recognition of the association between Samter’s syndrome and otological disease is important (26% of the cases) because it could also be responsive to systemic steroids which prevent progression to irreversible hearing loss or infectious otomastoiditis.
Improper Sexual Behaviors in Elders with Dementia Living in Residential Care
Authors: de Medeiros Kate , Rosenberg Paul B. , Baker Alva S. , Onyike Chiadi U.
Published: October 2008

Objectives: There exists little information describing the spectrum and correlations of sexual behaviors manifested by elders with dementia living in residential care. Methods: Data are from a retrospective case-control study of improper sexual behaviors manifested by 165 elders with dementia living in a residential care facility in 2005. Results: Three types of behavior were evident: (1) intimacy-seeking, (2) disinhibited, and (3) nonsexual. Intimacy-seeking behaviors were associated with Alzheimer disease, and disinhibited behaviors with non-Alzheimer dementias. Behavior type was associated with dementia severity. Conclusions: Delineation of the types of improper sexual behaviors occurring in dementia has practical implications for practice and research. Progress will require prospective studies with systematic ascertainment of cases and variables, and recruitment from large sampling frames.
Prenatal Diagnosis of a Fetal Intracranial Immature Teratoma
Authors: Köken Gülengül , Yılmazer Mehmet , Şahin Figen Kır , Coşar Emine , Aslan Adem , Şahin Önder , Haktanır Alpay
Published: October 2008

Congenital intracranial teratoma is a rare disease. A fetus with a congenital intracranial teratoma presenting with a hydrocephalus at 27 weeks’ gestation is presented. Prenatal ultrasonography and fetal magnetic resonance imaging demonstrated a huge, heterogenous intracranial mass including the infra- and supratentorial region and polyhydramnios. At 28 weeks’ gestation, a cesarean section was performed to avoid divisive operation during delivery. The infant died after 10 min from respiratory failure. Histological examination revealed the diagnosis of immature teratoma. Early detection of congenital intracranial tumors is crucial. The prognosis is poor with death usually occurring shortly after birth.
Deep Brain Stimulation Parameters Associated with Neuropsychological Changes in Subthalamic Nucleus Stimulation for Refractory Parkinson’s Disease
Authors: Schoenberg Mike R. , Mash Kathleen M. , Bharucha Kersi J. , Francel Paul C. , Scott James G.
Published: October 2008

Background/Aims: Parkinson’s disease (PD) is an idiopathic progressive neurological disorder. Improvement in motor function of PD patients has been established with subthalamic nucleus (STN) deep brain stimulation (DBS). While variations in DBS settings (i.e. amplitude, frequency and pulse width) on motor function have been explored, little data has evaluated the relationship of DBS settings on cognitive function. This study evaluated the extent to which DBS settings were associated with cognitive function. Methods: The study was a prospective clinical trial of STN DBS for the treatment of refractory PD. Twenty patients were evaluated once preoperatively and an average of 5 months following bilateral STN DBS. Measures included a test of motor disability, a neuropsychological test battery and subjective mood measures of anxiety and depression. Results: Motor function significantly improved following bilateral STN DBS. Compared to preoperative performance, verbal fluency declined while visuoconstructional skills improved. Amplitude and pulse width were significantly correlated with measures of cognitive function. Multiple regression found DBS stimulator settings, along with anxiety, to be significant predictors of cognitive measures. Conclusion: Increased amplitude and pulse width and decreased anxiety were associated with improved cognitive test scores. Although preliminary, these data have potential theoretical and clinical applications.
Virtually Peeling Off the Skull and Scalp: A Simple Way of Mapping the Superficial Cerebral Veins on the Brain Surface
Authors: Gong X.Y. , Higano S. , Mugikura S. , Umetsu A. , Murata T. , Kumabe T. , Takahashi S.
Published: October 2008

Purpose: A simple MRI postprocessing technique was developed to display superficial cerebral veins (SCVs) along with brain surface structures. Materials and Methods: Thirty-one consecutive patients with brain tumors were studied. All patients underwent brain MR examination, from which three-dimensional (3D) images were reconstructed. Simulation images of craniotomy were created by cutting away the signal from the skull and scalp at the region corresponding to the window planned for surgery. Detectability of the SCVs was evaluated by comparing the simulation images with intraoperative photographs. Reasons for those undetectable SCVs on simulation images of craniotomy were discussed. Results: Detectability of the SCVs >2 mm was 100%; those from 1 to 2 mm was 88.5%, and those from 0.5 to 1 mm 56.9%. Effacement of cortical sulci/subarachnoid space around the supposed craniotomy site, dural/meningeal contrast enhancement and insufficient spatial resolution of the source images were regarded as the main reasons for undetectable SCVs. Conclusion: Virtually peeling off the skull and scalp well demonstrates the SCVs along with brain surface structures. This simple technique can provide useful information about the SCVs and their relationships with cortical structures and tumors for preoperative surgical planning.
Critiques of Clinical Guidelines in Nephrology: Anaemia
Authors: Courtney A.E. , Maxwell A.P.
Published: October 2008

Chronic kidney disease (CKD) is characterised by reduced erythropoietin production and anaemia. The introduction in the late 1980s of recombinant human erythropoietin transformed the quality of life and the blood transfusion requirements of patients with advanced CKD, and several erythropoietin analogues or derivatives with the collective name of erythropoiesis-stimulating agents (ESAs) are now available. However, despite the treatment of hundreds of thousands of patients with ESAs there have still been relatively few randomised controlled trials comparing outcomes at pre-specified haemoglobin (Hb) concentrations. Several unanswered questions remain regarding the optimal use of ESAs, including the ideal target Hb level for an individual and a CKD population. The conclusion from the available interventional studies is that there is no evidence for a beneficial effect of complete correction of Hb and there is weak evidence of harm with an increase in cardiovascular events and mortality. This has prompted some renal advisory bodies to modify their guidance on ESA prescribing. This critique reviews current clinical guidelines and recommendations, their scientific basis, and identifies areas of controversy including the role of newer agents, the long-term safety of ESAs, the influence of the pharmaceutical industry, and the associated healthcare costs.
Cryptogenic Emboli in Patients with Patent Foramen Ovale or Atrial Septal Defect Associated with the Use of Nonsteroidal Anti-Inflammatory Drugs
Authors: Ferguson Michael A. , Mackay Steven M. , Ramchandani Suneil R. , Thurber John S. , Curran Michael J. , DeGraba Thomas J.
Published: October 2008

Background: Nonaspirin, nonsteroidal anti-inflammatory drugs (NANSAIDs) have been associated with arterial thromboembolic events in the general population. Our objective was to determine the prevalence of NANSAID use in patients diagnosed with cryptogenic emboli or paradoxical embolic events from a patent foramen ovale (PFO) or atrial septal defect (ASD) compared with a control population with an incidental PFO/ASD and no history of embolic events. Methods: We performed a retrospective case-control study of 90 age-matched patients to assess the association of NANSAIDs with cryptogenic arterial embolic events in patients with and without a history of PFO/ASD. Odds ratios (ORs) were obtained by χ2 analysis. Multivariate analysis was conducted with a logistical regression method. Results: Patients with cryptogenic embolic events had a high prevalence of prescription NANSAID use regardless of the presence of a PFO/ASD and were far more likely to have a history of NANSAID use than those with an incidentally discovered PFO/ASD and no history of arterial emboli (OR 4.30, 95% confidence interval 1.14–13.07, p = 0.01). Conclusions: Many patients previously diagnosed with paradoxical emboli may be experiencing the prothrombotic effects of NANSAIDs rather than a paradoxical mechanism for their arterial embolic event.
Systemic Inflammation following Hind-Limb Ischemia-Reperfusion Affects Brain in Neonatal Mice
Authors: Bianco-Batlles M. Daniela , Sosunov Alexander , Polin Richard A. , Ten Vadim S.
Published: October 2008

Antenatal and postnatal infection and inflammation are associated with neurological injury in neonates. However, no direct role for systemic inflammation in mediating neurodamage has been shown. The study was aimed to determine whether systemic inflammation following ischemia-reperfusion (IR) of an organ remotely located from the brain results in cerebral injury. Neonatal mice were subjected to 2 h of hind-limb IR. At 48 h of reperfusion, brains were examined for activation of microglia and caspase-3. Lungs were assessed for pulmonary edema and granulocyte infiltration. The levels of circulating inflammatory mediators were measured at 24 h of reperfusion. In a separate cohort of mice, changes in the cerebral and hind-limb blood flow were measured. All data were compared to that in sham mice. Compared to shams the degree of pulmonary edema in IR mice was 33% (p = 0.04) greater. This was associated with significantly (p = 0.0006) greater granulocytic infiltration and a markedly increased level of circulating cytokines. The brains of these same mice exhibited significantly (p = 0.02) greater numbers of caspase-3-immunopositive cells and activation of microglia compared to sham mice. These data indicate that systemic inflammation following IR in the organ remote from the brain can induce neuroinflammation and cerebral proapoptotic changes.
Use of a Fall Prevention Practice Guideline for Community-Dwelling Older Persons at Risk for Falling: A Feasibility Study
Authors: Milisen Koen , Geeraerts Annelies , Dejaeger Eddy
Published: October 2008

Background: Falls among older persons occur frequently and are a common cause of physical and psychological morbidity and healthcare utilization. The problem can be attributed to a complex interaction between health-related, behavioral and environmental factors. To ensure a uniform and evidence-based approach, a practice guideline was developed for fall prevention in community-dwelling older persons at risk for falls. Objective: To test the feasibility of integrating a fall prevention practice guideline into the daily practice of 4 primary healthcare disciplines, i.e. general practitioners, nurses, occupational therapists and physiotherapists. Methods: This was a descriptive study which was carried out by 10 local health networks located throughout Flanders. The subjects involved in the study were 99 primary care workers and 1,142 community-dwelling older patients (65 years or older) who could rise from a chair and transfer independently. For 6 months, primary care workers implemented our fall prevention guideline, which consisted of 3 parts (case finding, multifactorial in-depth assessment and interventions). After the 6-month trial phase, participating primary care workers were asked to complete a semistructured questionnaire to evaluate the feasibility of using the guideline in daily practice. Results: The average time spent on carrying out the guideline was 32.0 ± 14.0 min. Healthcare workers from all 4 disciplines considered case finding to be their responsibility. The picture was different for the evaluation of risk factors and interventions. Although 87.5% considered fall prevention to be an important issue, healthcare workers from different disciplines failed to agree about how to integrate the prevention guideline into daily practice. Perceived barriers to implementing the guideline were lack of time (57.3%), poor motivation of the target population (53.3%) and insufficient cooperation between healthcare workers (37.3%). Conclusion: A guideline can be used to initiate the integration of prevention strategies into daily practice. Case finding is feasible for all disciplines. Multifactorial assessment and interventions require specific task allocation, multidisciplinary cooperation and clear communication.
Evaluating Centering for Information Ordering Using Corpora
Authors: Karamanis Nikiforos , Mellish Chris , Poesio Massimo , Oberlander Jon
Published: October 2008

In this article we discuss several metrics of coherence defined using centering theory and investigate the usefulness of such metrics for information ordering in automatic text generation. We estimate empirically which is the most promising metric and how useful this metric is using a general methodology applied on several corpora. Our main result is that the simplest metric (which relies exclusively on NOCB transitions) sets a robust baseline that cannot be outperformed by other metrics which make use of additional centering-based features. This baseline can be used for the development of both text-to-text and concept-to-text generation systems.
Employing Migrant Domestic Workers in Urban Yemen: A New Form of Social Distinction
Authors: de Regt Marina
Published: October 2008

This article argues that employing migrant domestic workers has become a new form of social distinction in urban Yemen. The rapid social, economic and political changes of the past forty years have altered Yemen's system of social stratification. Formerly, one's racial descent and economic background determined the work they performed. Manual and service professions had a very low status and were only performed by the lowest social status groups. Nowadays other forms of social distinction have emerged. Although the economic situation in Yemen has deteriorated since the 1990s, the demand for paid domestic labour has increased. Yemeni women are reluctant to take up paid work as domestics, and middle and upper middle class families in urban areas employ migrant and refugee women, in particular from the Horn of Africa.
Protecting Muslim Women against Abuse of Polygamy in Malaysia: Legal Perspective
Authors: Kamaruddin Zaleha , Abdullah Raihanah
Published: October 2008

Polygamy remains a controversial issue not only in Malaysia but also in many Muslim countries around the world. From the legal perspective, Muslim men, who choose to enter into polygamous marriages and abuse it, largely due to the absence of eff ective measures taken to curtail the problems bring this about. In Malaysia, these steps include the incorporation of specific provisions controlling the practice of polygamy in the Islamic Family Law Enactments of each state. This move is considered as a step towards formulating better laws to control abuses in the practice of polygamy. This paper discusses the concept behind existing provisions and looks into adequacy of such laws. It also aims at identifying problems and provides suggestions on how women could remain protected within a polygamous set up.
Identifying Climatic Controls on Ring Width: The Timing of Correlations between Tree Rings and NDVI
Authors: Kaufmann R. K. , D’Arrigo R. D. , Paletta L. F. , Tian H. Q. , Jolly W. Matt , Myneni R. B.
Published: October 2008

The authors examine the effects of latitude and life history on the timing of relationships between satellite measures of normalized difference vegetation index (NDVI) and ground-based measures of tree-ring width in forests at mid- and high latitudes in the Northern Hemisphere. Results indicate a correlation between NDVI and tree rings over the entire growing season for all areas analyzed. For sites south of 40°N, a correlation appears in early spring and late fall while a correlation appears during summer months north of 40°N. For conifers, the correlation appears in summer while deciduous trees show the relationship during early spring and late fall. Of these two correlations, the effect of life history seems to dominate the effect of latitude. The timing of these correlations may help clarify the relationship between climate and tree rings and the effect of canopy duration on carbon uptake by trees.
Instability of Surface Quasigeostrophic Vortices
Authors: Carton Xavier
Published: October 2008

The instability of circular vortices is studied numerically in the surface quasigeostrophic (SQG) model, and their evolutions are compared with those of barotropically unstable 2D vortices. The growth rates in the SQG model evidence similarity with their barotropic counterparts for moderate radial gradients of temperature (or of vorticity in the 2D model). For stronger gradients, SQG vortices are more unstable than 2D vortices. The nonlinear, finite-amplitude evolutions of perturbed vortices provide evidence that moderately unstable, elliptically perturbed vortices form tripoles. When they are more unstable, they break into two dipoles. Weakly unstable vortices with triangular perturbations form transient quadrupoles that break; they stabilize only for large gradients of mean temperature. Finally, with square perturbations, pentapoles degenerate into dipoles, at least for the range of mean temperature gradients explored here. The analysis of nonlinear stabilizations reveals that the deformation of the vortex core and the leak of its temperature anomaly to the periphery are essential ingredients to stabilize the perturbation at finite amplitude. In conclusion, SQG vortex instability exhibits considerable similarity to the barotropic instability of 2D vortices.
Generation of Bulk Shear Spikes in Shallow Stratified Tidal Seas
Authors: Burchard Hans , Rippeth Tom P.
Published: October 2008

Recent finescale observations of shear and stratification in temperate shelf sea thermoclines show that they are of marginal stability, suggesting that episodes of enhanced shear could potentially lead to shear instability and diapcynal mixing. The bulk shear between the upper and lower boundary layers in seasonally stratified shelf seas shows remarkable variability on tidal, inertial, and synoptic time scales that has yet to be explained. In this paper observations from the seasonally stratified northern North Sea are presented for a time when the water column has a distinct two-layer structure. Bulk shear estimates, based on ADCP measurements, show a bulk shear vector that rotates in a clockwise direction at the local inertial period, with episodes of bulk shear spikes that have an approximately twice daily period, and occur in bursts that last for several days. To explain this observation, a simple two-layer model based on layer averaging of the one-dimensional momentum equation is developed, forced at the surface by wind stress and damped by (tidally dominated) sea bed friction. The two layers are then linked through an interfacial stress term. The model reproduces the observations, showing that the bulk shear spikes are a result of the alignment of the wind stress, tidal bed stress, and (clockwise rotating) bulk shear vectors. Velocity microstructure measurements are then used to confirm enhanced levels of mixing during a period of bulk shear spikes. A numerical study demonstrates the sensitivity of the spike generation mechanism to the local tidal conditions and the phasing and duration of wind events.