bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell and molecular mechanisms of insulin‐induced angiogenesis
Authors: Liu Yan , Petreaca Melissa , Martins‐Green Manuela 
Published: October 2008

AbstractAngiogenesis, the development of new blood vessel from pre‐existing vessels, is a key process in the formation of the granulation tissue during wound healing. The appropriate development of new blood vessels, along with their subsequent maturation and differentiation, establishes the foundation for functional wound neovasculature. We performed studies in vivo and used a variety of cellular and molecular approaches in vitro to show that insulin stimulates angiogenesis and to elucidate the signalling mechanisms by which this protein stimulates microvessel development. Mice skin injected with insulin shows longer vessels with more branches, along with increased numbers of associated α‐smooth muscle actin‐expressing cells, suggesting the appropriate differentiation and maturation of the new vessels. We also found that insulin stimulates human microvascular endothelial cell migration and tube formation, and that these effects occur independently of VEGF/VEGFR signalling, but are dependent upon the insulin receptor itself. Downstream signalling pathways involve PI3K, Akt, sterol regulatory element‐binding protein 1 (SREBP‐1) and Rac1; inhibition of these pathways results in elimination of endothelial cell migration and tube formation and significantly decreases the development of microvessels. Our findings strongly suggest that insulin is a good candidate for the treatment of ischaemic wounds and other conditions in which blood vessel development is impaired.
Differential involvement of the extracellular 6‐O‐endosulfatases Sulf1 and Sulf2 in brain development and neuronal and behavioural plasticity
Authors: Kalus Ina , Salmen Benedikt , Viebahn Christoph , Figura Kurt von , Schmitz Dietmar , D'Hooge Rudi , Dierks Thomas 
Published: October 2008

AbstractThe extracellular sulfatases Sulf1 and Sulf2 remove specific 6‐O‐sulfate groups from heparan sulfate, thereby modulating numerous signalling pathways underlying development and homeostasis. In vitro data have suggested that the two enzymes show functional redundancy. To elucidate their in vivo functions and to further address the question of a putative redundancy, we have generated Sulf1‐ and Sulf2‐deficient mice. Phenotypic analysis of these animals revealed higher embryonic lethality of Sulf2 knockout mice, which can be associated with neuroanatomical malformations during embryogenesis. Sulf1 seems not to be essential for developmental or postnatal viability, as mice deficient in this sulfatase show no overt phenotype. However, neurite outgrowth deficits were observed in hippocampal and cerebellar neurons of both mutant mouse lines, suggesting that not only Sulf2 but also Sulf1 function plays a role in the developing nervous system. Behavioural analysis revealed differential deficits with regard to cage activity and spatial learning for Sulf1‐ and Sulf2‐deficient mouse lines. In addition, Sulf1‐specific deficits were shown for synaptic plasticity in the CA1 region of the hippocampus, associated with a reduced spine density. These results reveal that Sulf1 and Sulf2 fulfil non‐redundant functions in vivo in the development and maintenance of the murine nervous system.
Influence of modifying and veneering the surface of ceramic abutments on cellular attachment and proliferation
Authors: Mustafa Kamal , Wennerberg Ann , Arvidson Kristina , Messelt Edvard Berger , Haag Per , Karlsson Stig 
Published: October 2008

AbstractObjectives: This in vitro study was aimed to investigate the attachment, spreading and proliferation of human gingival fibroblasts to milled and polished non‐veneered ceramic surfaces in alumina and zirconia and to ceramic surfaces veneered by two different types of porcelain baseliners.Materials and methods: Fibroblasts were cultured on discs of pressed alumina or zirconia, on discs which had been milled, on discs comprising alumina or zirconia which had been polished, on discs of alumina veneered with NobelRondo baseliner Al, on discs of zirconia veneered with Cercon‐S baseliner, and on alumina or zirconia discs veneered with the above baseliners and then polished. The surfaces were analyzed using an optical interferometer and scanning electron microscopy (SEM). Cell profile areas were measured using SEM and an image analyzer. Cell attachment was determined after 3 and 24 h as a ratio of the cell profiles and the total micrograph area and was expressed as percent of attachment. MTT analyses were undertaken to determine cellular attachment after 3 h of incubation and cellular proliferation after 7 days.Results: The polished zirconia specimens had the smoothest surface in terms of average height deviation (Sa=0.03 μm): the roughest were the zirconia specimens with milled surfaces (Sa=0.36 μm). The application of the baseliners resulted in surfaces smoother than those of the non‐veneered discs. The milled surfaces of both alumina and zirconia had significantly higher percentages of cell attachment and proliferation than the other surfaces whereas the milled surfaces in zirconia demonstrated better cellular attachment after 3 and 24 h of culture than the one in alumina. Fibroblasts attached and grew effectively on the surfaces veneered with NobelRondo throughout the experiments, whereas the zirconia surfaces veneered with Cercon‐S had the lowest percentage of cell attachment and proliferation.Conclusions: Although the roughness of all surfaces investigated was <0.4 μm, the study disclosed significant differences in cellular attachment and proliferation associated with the various surface modifications.
Two‐year prospective clinical comparison of immediate replacement vs. immediate restoration of single tooth in the esthetic zone
Authors: Palattella Piermario , Torsello Ferruccio , Cordaro Luca 
Published: October 2008

AbstractAim: To compare the immediate restoration of single implants in the esthetic zones performed on implants placed immediately after tooth extraction or 8 weeks later (immediate replacement vs. immediate restoration).Methods: Sixteen patients (10 women and 6 men) with a mean age of 35 years (ranging from 21 to 49 years old) were treated from 2004 to 2005 for single‐tooth replacement in the upper arch. The patients were randomly divided into two groups: in the test group patients received implants placed and restored (non‐occlusal loading) at the time of tooth extraction; in the control group implants were placed 8 weeks after tooth extraction and immediately restored. All the patients received tapered effect (TE) implants from the Straumann Dental Implant System. The following parameters were evaluated at the moment of provisional restoration (within 48 h after implant placement) and at the 2 years follow‐up visit: marginal bone resorption, papilla index, position of the mucosal margin. The implant stability quotient was measured at the moment of implant placement and at the moment of the delivery of the definitive restoration.Results: No statistically significant differences were found in any of the studied parameters between the test and the control groups (P>0.05). The implant stability quotient values between the test and control groups were significant (P<0.05) at the moment of implant placement but were no more significant at the loading of the definitive restoration (P>0.05).Conclusion: The results of the present study suggest that immediate replacement without functional loading may be considered a valuable therapeutic option for selected cases of single‐tooth replacement in the esthetic area when TE implants are used. Implant stability at the moment of implant placement is slightly inferior in the immediate replacement group, but it does not affect the treatment result.
Simple Disk-Based Method for Detection of
Klebsiella pneumoniae
Carbapenemase-Type β-Lactamase by Use of a Boronic Acid Compound
Authors: Doi Yohei , Potoski Brian A. , Adams-Haduch Jennifer M. , Sidjabat Hanna E. , Pasculle Anthony W. , Paterson David L. 
Published: October 2008

ABSTRACT

A disk potentiation method using carbapenems as substrates and 3-aminophenyl boronic acid as an inhibitor was evaluated for the detection of
Klebsiella pneumoniae
carbapenemase (KPC)-type β-lactamases. When combined with nonsusceptibility to ertapenem, the method was easy to perform and reliably differentiated isolates producing KPC-type β-lactamases from those producing other types of β-lactamases.
Critical Role for TSLC1 Expression in the Growth and Organ Infiltration of Adult T-Cell Leukemia Cells In Vivo
Authors: Dewan M. Zahidunnabi , Takamatsu Naofumi , Hidaka Tomonori , Hatakeyama Kinta , Nakahata Shingo , Fujisawa Jun-ichi , Katano Harutaka , Yamamoto Naoki , Morishita Kazuhiro 
Published: October 2008

ABSTRACT

Adult T-cell leukemia (ATL) is associated with human T-cell leukemia virus type 1 infection. The tumor suppressor lung cancer 1 (TSLC1) gene was previously identified as a novel cell surface marker for ATL, and this study demonstrated the involvement of TSLC1 expression in tumor growth and organ infiltration of ATL cells. In experiments using NOD/SCID/γc
null
mice, both leukemia cell lines and primary ATL cells with high TSLC1 expression caused more tumor formation and aggressive infiltration of various organs of mice. Our results suggest that TSLC1 expression in ATL cells plays an important role in the growth and organ infiltration of ATL cells.
Polymorphisms in the Interleukin-4 Receptor Gene are Associated with Better Survival in Patients with Glioblastoma
Authors: Scheurer Michael E. , Amirian E. , Cao Yumei , Gilbert Mark R. , Aldape Kenneth D. , Kornguth David G. , El-Zein Randa , Bondy Melissa L. 
Published: October 2008

Abstract
Purpose: Previous literature provides some evidence that atopic diseases, IgE levels, and inflammatory gene polymorphisms may be associated with risk of glioblastoma. The purpose of this study was to investigate the effects of certain inflammatory gene single nucleotide polymorphisms (SNP) on patient survival. Malignant gliomas are the most common type of primary brain tumor in adults, however, few prognostic factors have been identified.
Experimental Design: Using 694 incident adult glioma cases identified between 2001 and 2006 in Harris County, TX, we examined seven SNPs in the interleukin (IL)-4, IL-13, and IL-4 receptor (IL4R) genes. Cox proportional hazards regression was used to examine the association between the SNPs and overall and long-term survival, controlling for age at diagnosis, time between diagnosis and registration, extent of surgical resection, radiation therapy, and chemotherapy.
Results: We found that among high-grade glioma cases, IL4R rs1805016 (TT versus GT/GG) was significantly protective against mortality over time [hazard ratios (HR), 0.59; 95% confidence intervals (CI), 0.40-0.88]. The IL4R rs1805016 and rs1805015 TT genotypes were both found to be significantly associated with survival beyond 1 year among patients with high-grade glioma (HR, 0.44; 95% CI, 0.27-0.73 and HR, 0.63; 95% CI, 0.44-0.91, respectively). Furthermore, the IL4R haplotype analysis showed that SNPs in the IL4R gene may be interacting to affect long-term survival among high-grade glioma cases.
Conclusions: These findings indicate that polymorphisms in inflammation pathway genes may play an important role in glioma survival. Further research on the effects of these polymorphisms on glioma prognosis is warranted.
Pathways Mediating Resistance to Vascular Endothelial Growth Factor–Targeted Therapy
Authors: Ellis Lee M. , Hicklin Daniel J. 
Published: October 2008

Abstract
Vascular endothelial growth factor (VEGF)–targeted therapy has become an important treatment option for the management of a number of human malignancies. Unfortunately, a significant number of patients do not respond to VEGF-targeted therapy when used as a single agent or in combination with chemotherapy. Furthermore, the duration of benefit from VEGF-targeted therapy can be relatively short (weeks to months). Ultimately, the vast majority of patients who initially respond to therapy will develop resistance. To date, the molecular and cellular mechanisms associated with resistance to VEGF-targeted agents are poorly understood. The mechanisms of action of anti-VEGF therapy are diverse, and it is entirely possible that resistance mechanisms are similarly diverse and depend on the tumor type. A better understanding of these mechanisms will help in the selection of those patients that are more likely to benefit from VEGF-targeted therapy and also provide for the rational development of therapies that circumvent or overcome resistance.
Chemosensitivity and Stratification by a Five Monoclonal Antibody Immunohistochemistry Test in the NSABP B14 and B20 Trials
Authors: Ross Douglas T. , Kim Chung-yeul , Tang Gong , Bohn Olga L. , Beck Rodney A. , Ring Brian Z. , Seitz Robert S. , Paik Soonmyung , Costantino Joseph P. , Wolmark Norman 
Published: October 2008

Abstract
Purpose: To test the association between risk stratification and outcome in a prospectively designed, blinded retrospective study using tissue arrays of available paraffin blocks from the estrogen receptor–expressing, node-negative samples from the National Surgical Adjuvant Breast and Bowel Project B14 and B20 tamoxifen and chemotherapy trials.
Experimental Design: Tissue arrays were stained by immunohistochemistry targeting p53, NDRG1, SLC7A5, CEACAM5, and HTF9C. Risk stratification was done using predefined scoring rules, algorithm for combining scores, and cutoff points for low-risk, moderate-risk, and high-risk patient strata.
Results: In a univariate Cox model, this test was significantly associated with recurrence-free interval [HR, 1.3 (95% confidence interval, 1.1-1.6); P = 0.006]. In a multivariate model it contributed information independent of age, tumor size, and menopausal status (P = 0.007). The Kaplan-Meier estimates of the proportion of recurrence-free after 10 years were 73%, 86%, and 85% for the high-risk, moderate-risk, and low-risk groups (P = 0.001). The Kaplan-Meier estimates of the breast-cancer-specific-death rate were 23%, 10%, and 9% (P &lt; 0.0001). Exploratory analysis in patients ≥60 years old showed Kaplan-Meier estimates of the proportion of recurrence-free of 78%, 89%, and 92%. Both high-risk and low-risk groups showed significant improvement on treatment with cytotoxic chemotherapy.
Conclusions: Immunohistochemistry using five monoclonal antibodies assigns breast cancer patients to a risk index that was significantly associated with clinical outcome among the estrogen receptor–expressing, node-negative tamoxifen-treated patients. It seems that the test may be able to identify patients who have greater absolute benefit from adjuvant chemotherapy compared with unstratified patient populations. Exploratory analysis suggests that this test will be most useful in clinical decision making for postmenopausal patients.
A Polymorphism in the Complement ComponentC1qACorrelates with Prolonged Response Following Rituximab Therapy of Follicular Lymphoma
Authors: Racila Emilian , Link Brian K. , Weng Wen-Kai , Witzig Thomas E. , Ansell Stephen , Maurer Matthew J. , Huang Jian , Dahle Christopher , Halwani Ahmad , Levy Ronald , Weiner George J. 
Published: October 2008

AbstractPurpose: Complement may play a role in the clinical response to rituximab and other monoclonal antibody–based therapies of cancer. The purpose of this study was to explore the relationship between the C1qA[276] polymorphism and the clinical response to rituximab in patients with follicular lymphoma.Experimental Design: Genotyping for C1qA[276A/G] was done in 133 subjects with follicular lymphoma treated with single-agent rituximab, and correlation with clinical response was done using Cox regression analysis.Results: Prolonged remission was observed among subjects that responded clinically to rituximab therapy and were carriers of the A allele compared with homozygous G subjects. Homozygous G subjects had a time to progression of 282 days, whereas A-allele carriers had a time to progression of 708 days [hazard ratio, (HR), 2.5; 95% confidence interval (95% CI), 2.0-3.1; P = 0.02]. Among subjects who achieved complete remission, homozygous G subjects had a time to progression of 250 days, whereas A-allele carriers had a time to progression of 1,118 days (HR, 4.5; 95% CI, 4.1-4.8, P = 0.04). The difference persisted after controlling for CD32 and CD16 polymorphisms. In patients who responded to rituximab used as first-line agent, a linear trend was observed among the C1qA[276] genotypes, with homozygous A subjects achieving complete response at a higher rate compared with heterozygous or homozygous G subjects.Conclusions: Our findings indicate that polymorphisms in the C1qA gene may affect the clinical response and duration of response to rituximab therapy of follicular lymphoma. These results could have direct implications on designing antibodies with improved efficiency and enhance our understanding of the role of complement in monoclonal antibody therapy.
Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1genes
Authors: Gelsi-Boyer Véronique , Trouplin Virginie , Adélaïde José , Aceto Nicola , Remy Virginie , Pinson Stephane , Houdayer Claude , Arnoulet Christine , Sainty Danielle , Bentires-Alj Mohamed , Olschwang Sylviane , Vey Norbert , Mozziconacci Marie-Joëlle , Birnbaum Daniel , Chaffanet Max 
Published: October 2008

Abstract

Background
Chronic myelomonocytic leukemia (CMML) is a hematological disease close to, but separate from both myeloproliferative disorders (MPD) and myelodysplastic syndromes and may show either myeloproliferative (MP-CMML) or myelodysplastic (MD-CMML) features. Not much is known about the molecular biology of this disease.

Methods
We studied a series of 30 CMML samples (13 MP- and 11 MD-CMMLs, and 6 acutely transformed cases) from 29 patients by using Agilent high density array-comparative genomic hybridization (aCGH) and sequencing of 12 candidate genes.

Results
Two-thirds of samples did not show any obvious alteration of aCGH profiles. In one-third we observed chromosome abnormalities (e.g. trisomy 8, del20q) and gain or loss of genes (e.g. NF1, RB1 and CDK6). RAS mutations were detected in 4 cases (including an uncommon codon 146 mutation in KRAS) and PTPN11 mutations in 3 cases. We detected 11 RUNX1 alterations (9 mutations and 2 rearrangements). The rearrangements were a new, cryptic inversion of chromosomal region 21q21-22 leading to break and fusion of RUNX1 to USP16. RAS and RUNX1 alterations were not mutually exclusive. RAS pathway mutations occurred in MP-CMMLs (~46%) but not in MD-CMMLs. RUNX1 alterations (mutations and cryptic rearrangement) occurred in both MP and MD classes (~38%).

Conclusion
We detected RAS pathway mutations and RUNX1 alterations. The latter included a new cryptic USP16-RUNX1 fusion. In some samples, two alterations coexisted already at this early chronic stage.
Identification of the Weevil immune genes and their expression in the bacteriome tissue
Authors: Anselme Caroline , Pérez-Brocal Vicente , Vallier Agnès , Vincent-Monegat Carole , Charif Delphine , Latorre Amparo , Moya Andrés , Heddi Abdelaziz 
Published: October 2008

Abstract

Background

Persistent infections with mutualistic intracellular bacteria (endosymbionts) are well represented in insects and are considered to be a driving force in evolution. However, while pathogenic relationships have been well studied over the last decades very little is known about the recognition of the endosymbionts by the host immune system and the mechanism that limits their infection to the bacteria-bearing host tissue (the bacteriome).

Results

To study bacteriome immune specificity, we first identified immune-relevant genes of the weevil Sitophilus zeamais by using suppressive subtractive hybridization (SSH) and then analyzed their full-length coding sequences obtained by RACE-PCR experiments. We then measured immune gene expression in the bacteriome, and in the aposymbiotic larvae following S. zeamais primary endosymbiont (SZPE) injection into the hemolymph, in order to consider the questions of bacteriome immune specificity and the insect humoral response to symbionts. We show that larval challenge with the endosymbiont results in a significant induction of antibacterial peptide genes, providing evidence that, outside the bacteriome, SZPE are recognized as microbial intruders by the host. In the bacteriome, gene expression analysis shows the overexpression of one antibacterial peptide from the coleoptericin family and, intriguingly, homologs to genes described as immune modulators (that is, PGRP-LB, Tollip) were also shown to be highly expressed in the bacteriome.

Conclusion

The current data provide the first description of immune gene expression in the insect bacteriome. Compared with the insect humoral response to SZPE, the bacteriome expresses few genes among those investigated in this work. This local immune gene expression may help to maintain the endosymbiont in the bacteriome and prevent its invasion into insect tissues. Further investigations of the coleoptericin, the PGRP and the Tollip genes should elucidate the role of the host immune system in the maintenance and regulation of endosymbiosis.
Functional significance of the signal transduction pathways Akt and Erk in ovarian follicles: in vitro and in vivo studies in cattle and sheep
Authors: Ryan Kate E , Glister Claire , Lonergan Pat , Martin Finian , Knight Phil G , Evans Alexander CO 
Published: October 2008

Abstract

Background
The intracellular signalling mechanisms that regulate ovarian follicle development are unclear; however, we have recently shown differences in the Akt and Erk signalling pathways in dominant compared to subordinate follicles. The aim of this study was to investigate the effects of inhibiting Akt and Erk phosphorylation on IGF- and gonadotropin- stimulated granulosa and theca cell function in vitro, and on follicle development in vivo.

Methods
Bovine granulosa and theca cells were cultured for six days and stimulated with FSH and/or IGF, or LH in combination with PD98059 (Erk inhibitor) and/or LY294002 (Akt inhibitor) and their effect on cell number and hormone secretion (estradiol, activin-A, inhibin-A, follistatin, progesterone and androstenedione) determined. In addition, ovarian follicles were treated in vivo with PD98059 and/or LY294002 in ewes on Day 3 of the cycle and follicles were recovered 48 hours later.

Results
We have shown that gonadotropin- and IGF-stimulated hormone production by granulosa and theca cells is reduced by treatment with PD98059 and LY294002 in vitro. Furthermore, treatment with PD98059 and LY294002 reduced follicle growth and oestradiol production in vivo.

Conclusion
These results demonstrate an important functional role for the Akt and Erk signalling pathways in follicle function, growth and development.