bluuebunny/crossref_metadata_2025 huggingface dataset:
p16 expression in primary malignant melanoma is associated with prognosis and lymph node status
Authors: Mihic‐Probst Daniela , Mnich Christian D. , Oberholzer Patrick A. , Seifert Burkhardt , Sasse Bernd , Moch Holger , Dummer Reinhard
Published: December 2005

Lymph node (LN) status is an important prognostic factor in melanoma patients. p16 expression and proliferation rate (MIB‐1) of primary melanomas have been suggested as a marker of metastatic potential. In this study, the correlation of p16 expression and the proliferation rate (MIB‐1) with LN status and tumor‐specific survival was investigated in primary melanomas. MIB‐1 and p16 expression were analyzed by immunohistochemistry in 64 patients with primary cutaneous melanoma. Thirty four nevi were used as control. All patients underwent sentinel lymph node staging. Three different p16 staining patterns were observed: a combination of nuclear and cytoplasmic staining, only cytoplasmic staining and absence of p16 expression. All 34 nevi displayed a nuclear and cytoplasmic p16 staining, whereas p16 was negative in 14 of 64 (22%) melanomas. The level of p16 expression gradually decreased from benign nevi to melanoma without metastasis to melanoma with metastasis. There was a significant correlation between cytoplasmic p16 expression and absence of metastasis (p < 0.05). Death of disease correlated with absence of p16 immunostaining (p = 0.01). MIB‐1 expression was not associated with survival. These results confirm the relevance of p16 expression as a prognostic marker in melanoma patients. In addition, it was shown that cytoplasmic immunostaining for p16 in primary melanoma might serve as a predictor of the LN status. Therefore, immunohistochemical evaluation for p16 expression is of potential value for treatment planning in melanoma surgery. © 2005 Wiley‐Liss, Inc.
Comparison of DNA hypermethylation patterns in different types of uterine cancer: Cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma
Authors: Kang Sokbom , Kim Jae Weon , Kang Gyeong Hoon , Lee Sun , Park Noh Hyun , Song Yong Sang , Park Sang Yoon , Kang Soon Beom , Lee Hyo Pyo
Published: December 2005

The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite‐modification technique and methylation‐specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p < 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs (80.6% vs. 43.3%, p = 0.001; 77.4% vs. 46.7%, p = 0.005), whereas HLTF and TIMP3 were more frequently methylated in CAs (3.2% vs. 43.3%, p < 0.001; 8.1% vs. 53.3%, p = 0.001). The hypermethylations of RASSF1A and APC were more frequent in CAs than in CSCCs, but this was not significant (9.7% vs. 33.3%, p = 0.008; and 14.5% vs. 40.0%, respectively, p = 0.009). In addition, RASSF1A hypermethylation was significantly more frequent in EAs than in CAs (81.0% vs. 33.3%, p = 0.001). In conclusion, the existence of these unique methylation patterns in these cancers suggests that their tumorigenesis may involve different epigenetic mechanisms. © 2005 Wiley‐Liss, Inc.
Tobacco use, body mass index and the risk of malignantlymphomas—A nationwide cohort study in Sweden
Authors: Fernberg Pia , Odenbro Åsa , Bellocco Rino , Boffetta Paolo , Pawitan Y Yudi , Adami Johanna
Published: December 2005

In the search for risk factors involved in the etiology of lymphoproliferative malignancies there is still inconsistent evidence regarding effects of smoking tobacco, and the role of smokeless tobacco is poorly investigated. New evidence indicates that excess body weight increases the risk of NHL and HD. To determine if tobacco use of various forms and high Body Mass Index (BMI) affect the occurrence of these neoplasms, we conducted a prospective cohort study on over 330,000 Swedish construction workers included in the Construction Industry Working Environment and Health program. Information on smoking, snuff dipping, height and weight was gathered by self administered questionnaires together with personal interviews. Cancer incidence was ascertained through the year 2000 by record linkage to the nationwide Swedish Cancer Registry, Migration Registry and Cause of Death Registry. At the end of follow up, 1,309 subjects had been diagnosed with NHL (including chronic lymphocytic leukemia) and 205 with HD respectively. Age adjusted incidence rate ratios were computed using Cox proportional Hazard regression modeling. Smoking cigarette, pipe or cigar was not associated with NHL or HD. There was no evidence indicating a relation between quantity and duration of smoking and NHL or HD risk. No link was found between NHL and usage of smokeless tobacco. Having a BMI of 30 or higher did not convey excess risk of developing NHL or HD compared to normal weight (BMI 18.6–24.9). We conclude that tobacco smoking and high BMI do not entail an increased risk of NHL and HD. Our findings of a relation between the duration of snuff dipping and HD need further investigation. © 2005 Wiley‐Liss, Inc.
Prognostic significance of osteopontin expression in human prostate cancer
Authors: Forootan Shiva S. , Foster Christopher S. , Aachi Vijay R. , Adamson Janet , Smith Paul H. , Lin Ke , Ke Youqiang
Published: December 2005

To test the hypothesis that expression of osteopontin (OPN), an integrin‐binding glycoprotein, can independently predict the potential aggressiveness of prostate cancer, the status of OPN expression in benign and malignant prostate cancer cell lines and tissues was analysed by Western blot and immunohistochemistry. Amongst the four prostate cell lines analysed, the level of OPN expressed in the benign PNT‐2 cells was set at 1, the relative level of OPN expressed in the weakly malignant cell line LNCaP was increased to 1.5. In the highly malignant cell lines Du‐145 and PC‐3, the level of OPN expression was further increased to 2.9 and 4.4, respectively. An increased expression of OPN was also observed in the prostate tissue samples. When the level of OPN in normal tissue was set at 1, its level in benign prostate hyperplasia (BPH) was similar at 0.99 ± 0.2, whereas the OPN level in the highly malignant carcinoma tissue was greatly increased by nearly 6‐fold to 5.9 ± 0.3. Amongst the 116 cases examined immunocytochemically, of the 10 normal cases, 3 (30%) were unstained and 7 (70%) stained weakly positive (+). Amongst the 36 BPH samples, 32 (89%) stained weakly positive (+) and 4 (11%) were unstained (−). For the 70 carcinomas analysed, 31 (44%) stained strongly positive (+++), 20 (29%) stained moderately positive (++) and 19 (27%) stained weakly positive (+). These results showed that the level of OPN expressed between the normal and the BPH samples was not significantly different (Fisher's exact test, p = 0.16). However, in comparison to that in the BPH samples, the expression of OPN in the carcinoma tissues was significantly increased (Chi‐square test, p < 0.0001). Kaplan‐Meier survival analysis showed that the increased level of OPN expression was significantly (n = 70, p = 0.03) associated with reduced survival time of the patients. The OPN expression was increased with the increasing Gleason scores of the carcinomas (Chi‐square test, p < 0.001). The results in our study support our hypothesis and suggest that the increased OPN level may be involved in the malignant transformation of prostate epithelial cells and OPN expression level is an important determinant for patient survival. © 2005 Wiley‐Liss, Inc.
Nuclear Maspin expression is associated with response to adjuvant 5‐fluorouracil based chemotherapy in patients with stage III colon cancer
Authors: Dietmaier Wolfgang , Bettstetter Marcus , Wild Peter J. , Woenckhaus Matthias , Rümmele Petra , Hartmann Arndt , Dechant Stefan , Blaszyk Hagen , Pauer Armin , Klinkhammer‐Schalke Monika , Hofstädter Ferdinand
Published: December 2005

Maspin, a member of the Serpin protease inhibitor family, is overexpressed in poorly differentiated colorectal tumors and more frequently found in tumors with microsatellite instability. Immunohistochemical nuclear Maspin staining is predominantly seen in tumor cells at the invasion front of such cancers, suggesting that this molecule is associated with local tumor cell infiltration and aggressiveness. In a retrospective study, we studied nuclear Maspin expression as a potential prognostic tool in a total of 172 primary stage III colon cancers by immunohistochemistry. Of those 172 patients, 76 were treated by surgery only, and 96 patients received additional adjuvant 5‐fluorouracil (5‐FU) based chemotherapy. Nuclear Maspin expression was an independent adverse prognostic factor for overall survival in our patient cohort (hazard ratio 2.08; 95% CI, 1.13–3.81; p = 0.018). However, patients with primary tumors expressing Maspin in the nucleus showed a significant treatment benefit from 5‐FU chemotherapy (hazard ratio 0.384; 95% CI, 0.188–0.784; p = 0.009) compared to adjuvantly treated patients whose tumors did not express this molecule. Nuclear Maspin expression is highly predictive of 5‐FU chemotherapy response in patients with advanced stage colon cancer. Patients with negative immunhistochemical Maspin expression do not benefit from 5‐FU treatment and may be candidates for an alternative (non‐5‐FU based) adjuvant therapy regime. © 2005 Wiley‐Liss, Inc.
Long‐term survival of T1 and T2 lymph node‐negative breast cancer patients according to mitotic activity index: A population‐based study
Authors: Louwman W.J. , van Beek M.W.P.M. , Schapers R.F.M. , Nolthenius‐Puylaert M.B.C.J.E. Tutein , van Diest P.J. , Roumen R.M. , Coebergh J.W.W.
Published: December 2005

Node‐negative breast cancer patients have a relatively good prognosis, but eventually one‐third will die of the disease. Thus, prognostic factors to identify the high‐risk group among these patients are needed. We retrospectively determined the Mitotic Activity Index (MAI) for a large series of node‐negative breast cancer patients (n = 468) with tumours smaller than 5 cm, who only received locoregional treatment. Patients were followed for up to 29 years; crude and relative survival were calculated, both univariate and multivariate. Relative survival differed significantly according to MAI (p = 0.05), the difference occurred in the first 5 years after diagnosis and remained constant thereafter. After adjustment, MAI still significantly affected relative survival (RER, 1.9; 95% CI, 1.1–3.5). Tumour size also increased the risk, but this was not statistically significant (RER, 1.5; 95% CI, 0.8–2.7). Survival of patients with a T1 tumour and MAI < 10 was similar to that for the general population in the first 5 years after diagnosis. In conclusion, MAI significantly predicted long‐term survival for T1/T2N0 breast cancer. Adjuvant systemic therapy appears to have little benefit for node‐negative breast cancer patients with a T1 tumour, regardless of the MAI. For those with a T2 tumour and a MAI ≥ 10 systemic therapy might have reduced mortality. The need for close surveillance of node‐negative breast cancer patients with a T1 tumour and MAI <10 seems limited. © 2005 Wiley‐Liss, Inc.
Insulin‐like growth factor‐I, insulin‐like growth factor binding protein‐3 and the risk of fibrocystic breast conditions among Chinese women
Authors: Chen Chu , Doherty Jennifer A. , Lewis S. Kay , Ray Roberta M. , Gao Dao Li , Stalsberg Helge , Feng Ziding , Thomas David B.
Published: December 2005

We investigated whether circulating insulin‐like growth factor‐I (IGF‐I) and insulin‐like growth factor binding protein‐3 (IGFBP‐3) levels are associated with the risk of fibrocystic breast conditions (FBC), in a case‐control study nested within a randomized trial of breast self‐examination conducted in Shanghai, China. Participants were enrolled during 1989–1991 and were followed over 10 years for the development of breast diseases. Controls (n = 897) were frequency‐matched by age to cases (n = 451), who were diagnosed with FBC between 1995 and 2000. Circulating IGF‐I and IGFBP‐3 levels and their molar ratio were positively associated with risk of FBC. The odds ratios (ORs) and 95% confidence intervals (CI) for the upper fourth of the distribution compared to the lowest fourth for IGF‐I, IGFBP3 and their molar ratio were 3.02 (2.02–4.52), 1.92 (1.37–2.71) and 2.26 (1.52–3.36), respectively. The strength of the association between IGF‐I levels and FBC was attenuated after adjustment for IGFBP‐3 and that for IGFBP‐3 was largely eliminated after adjustment for IGF‐I. Increasing levels of IGF‐I were particularly associated with increasing risk of FBC with proliferative elements (ORs and 95% CIs for the 2nd, 3rd and upper fourth of the distribution of IGF‐I: 3.13 (1.50–6.53), 4.57 (2.22–9.39) and 6.30 (3.08–12.89), compared with the lowest fourth. Our results suggest that elevated levels of IGF‐I may contribute to the development of FBC. © 2005 Wiley‐Liss, Inc.
Genome variation of human papillomavirus types: Phylogenetic and medical implications
Authors: Bernard Hans‐Ulrich , Calleja‐Macias Itzel E. , Dunn S. Terence
Published: December 2005

Human papillomaviruses (HPVs) are described as “types” based on their genome sequences and identified by a number. For example, HPV‐6 is associated with genital warts, and HPV‐16 with anogenital cancers. The genomes of many HPV types have been reisolated, sequenced and compared to reference “prototypes” countless times by laboratories throughout the world. It was found that each HPV type occurs in the form of “variants”, identified by about 2% nucleotide differences in most genes and 5% in less conserved regions. Less than 100 variants of any HPV type have been detected, a scenario that is very different from the quasi‐species formed by many RNA viruses. The variants of each HPV type form phylogenetic trees, and variants from specific branches are often unique to specific ethnic groups. Immigrant populations contain, depending on their respective ethnic origins, mixtures of variants. The absence of HPV genomes intermediate to specific types show that all HPV types existed already when humans became a species. Consequently, humans had always suffered from lesions like anogenital cancer, genital warts and common warts. A growing number of epidemiological, etiological and molecular data suggest that variants of the same HPV type are biologically distinct and may confer differential pathogenic risks. Since the distribution of some variants of HPV‐16 and 18 correlates with the distribution of human populations that have an increased risk to develop anogenital cancer, the study of HPV type variation may point to one of the reasons for the higher incidence rates of these lesions in specific cohorts. © 2005 Wiley‐Liss, Inc.
The clinical significance of MAGEA3 expression in pancreatic cancer
Authors: Kim Joseph , Reber Howard A. , Hines Oscar J. , Kazanjian Kevork K. , Tran Andy , Ye Xing , Amersi Farin F. , Martinez Steve R. , Dry Sarah M. , Bilchik Anton J. , Hoon Dave S.B.
Published: December 2005

The MAGEA gene family that encodes cancer testis antigens is differentially expressed in many cancers. Though MAGEA3 expression has been detected in gastrointestinal malignancies, its role in pancreatic ductal adenocarcinoma (PDAC) has not been well established. We assessed 57 patients who underwent intent‐to‐cure surgery for PDAC. Total RNA from paraffin‐embedded pancreatic tumors was extracted and assessed for MAGEA3 gene expression by an optimized probe‐based quantitative real‐time RT‐PCR (qRT) assay. MAGEA3 gene expression was detected by qRT in 25 (44%) patients. For the entire cohort, detection of MAGEA3 expression was associated with significantly decreased overall survival (median, 16 vs 33 months; log‐rank, p = 0.032). When clinicopathologic factors, including age, gender, stage, tumor extent, lymph node metastasis, tumor grade, perineural invasion and lymphovascular invasion were assessed by univariate analysis, MAGEA3 gene expression and tumor grade were significant prognostic factors for poor survival (HR 2.1, 95% CI: 1.0–4.4, p = 0.041; and HR 3.7, 95% CI: 1.8–7.6, p = 0.0004, respectively). Immunohistochemistry (IHC) was performed and confirmed MAGEA3 protein in PDAC specimens. In conclusion, MAGEA3 is differentially expressed in patients with PDAC; its expression correlates with significantly worse survival. Molecular assessment for MAGEA3 should be considered to improve prognostic evaluation and to identify eligible patients for potential immune‐based therapy. © 2005 Wiley‐Liss, Inc.
Multidrug resistance‐1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia
Authors: Kim Dong Hwan , Park Jae Yong , Sohn Sang Kyun , Lee Nan Young , Baek Jin Ho , Jeon Seok Bong , Kim Jong Gwang , Suh Jang Soo , Do Young Rok , Lee Kyu Bo
Published: December 2005

Multidrug resistance‐1 (MDR‐1) gene single nucleotide polymorphisms (SNPs) have been identified as associated with the treatment outcomes of acute myeloid leukemia (AML) in Caucasians; yet, similar evidence is lacking for Asian populations. A total of 101 AML patients were enrolled in the current study. Two MDR1 SNPs (C3435T and G2677T/A) were analyzed with PCR/RFLP assay. As regards C3435T polymorphism, C/C genotype was significantly correlated with lower functional P‐glycoprotein (P‐gp) activity in leukemic blasts (7.5%) compared with C/T (10.7%) or T/T genotype (19.9%, p = 0.029). In genotypic analyses, C/C at −3435 (p = 0.05) and G/G at −2677 (p = 0.04) were strongly associated with a higher probability of complete remission (CR). In addition, the 3‐year event‐free survival (EFS) was higher in G/G genotype at −2677 (60.6%) than nonG/G (21.9%; p = 0.0241), in C/C at −3435 was higher than nonC/C genotype (p = 0.0139), and was higher in GC haplotype homozygote (58.2%) than nonGC homozygote (22.6%; p = 0.0427). In a multivariate analysis, the group without GC haplotype showed worse EFS (p = 0.030), with unfavorable cytogenetic risk (p = 0.008). However, no differences were noted in overall survival according to the MDR1 SNPs (p = 0.491 for C3435T and p = 0.955 for G2677T/A). © 2005 Wiley‐Liss, Inc.
Interatomic potential models for natural apatite crystals: Incorporating strontium and the lanthanides
Authors: Rabone J. A. L. , De Leeuw N. H.
Published: December 2005

A comprehensive set of interatomic potential parameters for modeling natural apatite crystals is presented. These potentials build on those previously used in research on apatites with new potentials fitted empirically to crystal structures and their properties using the GULP program. We demonstrate that the new potentials produce good models for the different compounds used for fitting, as well as for several natural apatites. Also presented are predicted enthalpies of mixing of strontium and calcium apatites and predicted cation site preferences in strontium calcium fluorapatite. © 2005 Wiley Periodicals, Inc. J Comput Chem 27: 253–266, 2006
Application of standard DFT theory for nonbonded interactions in soft matter: Prototype study of poly‐para‐phenylene
Authors: Alves‐Santos Marcelo , Dávila Liliana Y. A. , Petrilli Helena M. , Capaz Rodrigo B. , Caldas Marília J.
Published: December 2005

We present a detailed analysis of the application of density functional theory (DFT) methods to the study of structural properties of molecular and supramolecular systems, using as a paradigmatic example three para‐phenylene‐based systems: isolated biphenyl, single chain poly‐para‐phenylene, and crystalline biphenyl. We use different functionals for the exchange correlation potential, the local density (LDA), and generalized gradient approximations (GGA), and also different basis sets expansions, localized, plane waves (PW), and mixed (localized plus PW), within the reciprocal space formulation for the hamiltonian. We find that regardless of the choice of basis functions, the GGA calculations yield larger interring distances and torsion angles than LDA. For the same XC approximation, the agreement between calculations with different basis functions lies within 1% (LDA) or 0.5% (GGA) for distances, and while PW and mixed basis calculations agree within 1° for torsion angles, the localized basis results show larger angles by ≃ 8° and a nonmonotonic dependence on basis size, with differences within 6°. The most prominent features, namely the torsion between rings for isolated molecule and infinite chain, and planarity for the molecule in crystalline environment, are well reproduced by all DFT calculations. © 2005 Wiley Periodicals, Inc. J Comput Chem 27: 217–227, 2006
Inhibition of collagen gene expression by interferon‐γ: Novel role of the CCAAT/enhancer binding protein β (C/EBPβ)
Authors: Ghosh Asish K , Bhattacharyya Swati , Mori Yasuji , Varga John
Published: December 2005

By inhibiting collagen synthesis, interferon‐γ (IFN‐γ) plays a key role in maintaining connective tissue homeostasis, but the mechanisms are not well‐understood. In addition to intracellular signaling through the canonical JAK–STAT transduction pathway, IFN‐γ was recently shown to regulate gene expression via the CCAAT/enhancer‐binding protein β (C/EBPβ) as well. Because C/EBPβ is a crucial mediator of immune and inflammatory responses, and has been implicated in regulation of collagen synthesis by tumor necrosis factor‐α, we examined its role in the inhibitory effects of IFN‐γ. The results demonstrated that IFN‐γ caused increased C/EBPβ expression in dermal fibroblasts and enhanced its binding to cognate DNA sequences in the α2(I) procollagen gene (COL1A2) promoter in vitro and in vivo. Disruption of C/EBP binding by deletion or site‐directed mutagenesis abrogated the inhibition of collagen promoter activity in transient transfection assays, as did cotransfection with dominant negative C/EBPβ, indicating a functional role of cellular C/EBPβ in mediating the IFN‐γ response. Rapid phosphorylation of the ERK1/2 MAP kinases induced by IFN‐γ was accompanied by phosphorylation and nuclear translocation of cellular C/EBPβ, and pretreatment of fibroblasts with ERK1/2 kinase inhibitor blocked C/EBPβ phosphorylation, as well as inhibition of COL1A2 promoter activity, elicited by IFN‐γ. These results provide compelling evidence for a novel C/EBPβ‐dependent IFN‐γ signaling pathway responsible for inhibition of collagen gene transcription. Taken together with recent reports, the findings indicate that intracellular pathways mediating negative regulation of collagen synthesis in response to distinct inflammatory signals that converge on C/EBPβ. J. Cell. Physiol. 207: 251–260, 2006. © 2005 Wiley‐Liss, Inc.
Tetraploidy/aneuploidy and stem cells in cancer promotion: The role of chromosome passenger proteins
Authors: Nguyen Hao G. , Ravid Katya
Published: December 2005

While polyploidy, a state of having fully duplicated sets of chromosomes per cell, has been described in normally developing bone marrow megakaryocytes or as an adaptive response in other cell types, aneuploidy is never detected in normal cells. Tetraploidy or aneuploidy can be induced by several signals and it is highly prevalent in different forms of cancers, suggesting a role for this cell cycle state in promoting cellular transformation. Investigations suggested that loss of heterozygosity of cancer‐related genes in stem cells might contribute to genetic instability in progeny cells and to subsequent cancer development. Deregulated expression of chromosome passenger proteins, such as Aurora kinases or Survivin, is a hallmark of various cancers, and experimentally induced changes in these regulators can promote tetraploidy or aneuploidy and loss of heterozygosity. Our studies described an induction of tetraploidy/aneuploidy by a stable form of Aurora‐B, leading to acquisition of transformation properties. It is intriguing to speculate that in some cancers, tetraploidy/aneuploidy induced by deregulated expression of a mitotic regulator represents a primary event that leads to unbalanced expression of a cluster of crucial genes and to cellular transformation. J.Cell.Physiol. © 2005 Wiley‐Liss, Inc.
A scoring system based on the expression of six surface molecules allows the identification of three prognostic risk groups in B‐cell chronic lymphocytic leukemia
Authors: Zucchetto Antonella , Bomben Riccardo , Dal Bo Michele , Sonego Paolo , Nanni Paola , Rupolo Maurizio , Bulian Pietro , Dal Maso Luigino , Del Poeta Giovanni , Del Principe Maria Ilaria , Degan Massimo , Gattei Valter
Published: December 2005

We have previously identified 12 surface antigens whose differential expression represented the signature of B‐cell chronic lymphocytic leukemia (B‐CLL) subsets with different prognosis. In the present study, expression data for these antigens, as determined in 137 B‐CLL cases, all with survivals, were utilized to devise a comprehensive immunophenotypic scoring system of prognostic relevance for B‐CLL patients. In particular, univariate z score was employed to identify the markers with greater prognostic impact, while maximally selected log‐rank statistics were chosen to define the optimal cut‐off points capable to split patients into two groups with different survivals. A weighted immunophenotypic scoring system was developed by integrating results from these analyses. Six antigens were selected: three positive prognosticators (CD62L, CD54, CD49c) and three negative prognosticators (CD49d, CD38, CD79b), with cut‐off values ranging from 30% to 50% of positive cells. By weighing the expression of each marker according to its statistical power, a complete scoring system, with point values comprised between 0 (complete absence of phenotypic conditions associated with good prognosis) and 9 (all the phenotypic conditions associated with good prognosis fulfilled), allowed to split the whole set of B‐CLL patients, into three distinctive prognostic groups (P = 4.78 × 10−11) with high‐ (score 0–3), intermediate‐ (score 4–6), and low‐ (score 7–9) risk of death. The three risk groups showed different distribution of cases as for Rai's stages, IgVH mutations, and ZAP‐70 expression. The proposed immunophenotypic scoring system may be an additional useful tool in routine diagnostic/prognostic procedures for B‐CLL. J. Cell. Physiol. 207: 354–363, 2006. © 2005 Wiley‐Liss, Inc.
Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs
Authors: Grayson Warren L. , Zhao Feng , Izadpanah Reza , Bunnell Bruce , Ma Teng
Published: December 2005

Low oxygen tension is thought to be an integral component of the human mesenchymal stem cell (hMSC) native bone marrow microenvironment. HMSC were cultured under physiologically relevant oxygen environments (2% O2) in three‐dimensional (3D) constructs for up to 1 month in order to investigate the combined effects of chronic hypoxia and 3D architecture on hMSC tissue‐development patterns. Hypoxic hMSC exhibited an extended lag phase in order to acclimatize to culture conditions. However, they subsequently proliferated continuously throughout the culture period, while maintaining significantly higher colony‐forming unit capabilities and expressing higher levels of stem cell genes than hMSC cultured at 20% O2 (normoxic) conditions. Upon induction, hypoxic hMSC also expressed higher levels of osteoblastic and adipocytic differentiation markers than normoxic controls. Hypoxia induced increased total protein levels in hMSC throughout the culture period, as well as significantly different fibronectin expression patterns suggesting that oxygen levels can significantly affect tissue‐development patterns. Importantly, hMSC maintained the ability to thrive in prolonged hypoxic conditions suggesting that hypoxia may be an essential element of the in vivo hMSC niche. Further studies are required to determine how variations in cellular characteristics and ECM expression impact on the physiological properties of the engineered tissue, yet these results strongly indicate that oxygen tension is a key parameter that influences the in vitro characteristics of hMSC and their development into tissues. J. Cell. Physiol. 207: 331–339, 2006. © 2005 Wiley‐Liss, Inc.
Hyaluronan‐based polymer scaffold modulates the expression of inflammatory and degradative factors in mesenchymal stem cells: Involvement of Cd44 and Cd54
Authors: Lisignoli Gina , Cristino Sandra , Piacentini Anna , Cavallo Carola , Caplan Arnold I. , Facchini Andrea
Published: December 2005

Hyaluronan (HA), in the bone marrow stroma, is the major non‐protein glycosaminoglycan component of extracellular matrix (ECM) involved in cell positioning, proliferation, differentiation as well as in receptor‐mediated changes in gene expression. Repair of bone and regeneration of bone marrow is dependent on ECM, inflammatory factors, like chemokines and degradative factors, like metalloproteinases. We analyzed the interaction between human mesenchymal stem cells (h‐MSCs) and a three‐dimensional (3‐D) HA‐based scaffold in vitro. The expression of CXC chemokines/receptors, CXCL8 (IL‐8)/CXCR1‐2, CXCL10 (IP‐10)/CXCR3, CXCL12 (SDF‐1)/CXCR4, and CXCL13 (BCA‐1)/CXCR5, and metalloproteinases/inhibitors MMP‐1, MMP‐3, MMP‐13/TIMP‐1 were evaluated in h‐MSCs grown on plastic or on HA‐based scaffold by Real‐time PCR, ELISA, and immunocytochemical techniques. Moreover, the expression of two HA receptors, CD44 and CD54, was analyzed. We found both at mRNA and protein levels that HA‐based scaffold induced the expression of CXCR4, CXCL13, and MMP‐3 and downmodulated the expression of CXCL12, CXCR5, MMP‐13, and TIMP‐1 while HA‐based scaffold induced CD54 expression but not CD44. We found that these two HA receptors were directly involved in the modulation of CXCL12, CXCL13, and CXCR5. This study demonstrates a direct action of a 3‐D HA‐based scaffold, widely used for cartilage and bone repair, in modulating both h‐MSCs inflammatory and degradative factors directly involved in the engraftment of specific cell types in a damaged area. Our data clearly demonstrate that HA in this 3‐D conformation acts as a signaling molecule for h‐MSCs. J. Cell. Physiol. 207: 364–373, 2006. © 2005 Wiley‐Liss, Inc.
Elastic fiber macro‐assembly is a hierarchical, cell motion‐mediated process
Authors: Czirok Andras , Zach Julia , Kozel Beth A. , Mecham Robert P. , Davis Elaine C. , Rongish Brenda J.
Published: December 2005

Elastic fibers are responsible for the extensibility and resilience of many vertebrate tissues, and improperly assembled elastic fibers are implicated in a number of human diseases. It was recently demonstrated that in vitro, cells first secrete tropoelastin into a punctate pattern of globules. To study the dynamics of macroassembly, that is, the assembly of the secreted tropoelastin globules into elastic fibers, we utilized long‐term time‐lapse immunofluorescence imaging and a tropoelastin p Timer fusion protein, which shifts its fluorescence spectrum over time. Pulse‐chase immunolabeling of the fibroblast‐like RFL‐6 cells demonstrates that tropoelastin globules aggregate in a hierarchical manner, creating progressively larger fibrillar structures. By analyzing the correlation between cell and extracellular matrix movements, we show that both the aggregation process and shaping the aggregates into fibrillar form is coupled to cell motion. We also show that the motion of non‐adjacent cells becomes more coordinated as the physical size of elastin‐containing aggregates increases. Our data imply that the formation of elastic fibers involves the concerted action and motility of multiple cells. J. Cell. Physiol. 207: 97–106, 2006. © 2005 Wiley‐Liss, Inc.
All the three ParaHox genes are present in Nuttallochiton mirandus (Mollusca: polyplacophora): evolutionary considerations
Authors: Barucca Marco , Biscotti Maria A. , Olmo Ettore , Canapa Adriana
Published: December 2005

The ParaHox gene cluster contains three homeobox genes, Gsx, Xlox and Cdx and has been demonstrated to be an evolutionary sister of the Hox gene cluster. Among deuterostomes the three genes are found in the majority of taxa, whereas among protostomes they have so far been isolated only in the phylum Sipuncula.

We report the partial sequences of all three ParaHox genes in the polyplacophoran Nuttallochiton mirandus, the first species of the phylum Mollusca where all ParaHox genes have been isolated. This finding has phylogenetic implications for the phylum Mollusca and for its relationships with the other lophotrochozoan taxa. J. Exp. Zool. (Mol. Dev. Evol.) 306B, 2006. © 2005 Wiley‐Liss, Inc.
Imaging myocardial fiber disarray and intramural strain hypokinesis in hypertrophic cardiomyopathy with MRI
Authors: Tseng Wen‐Yih I. , Dou Jiangang , Reese Timothy G. , Wedeen Van J.
Published: December 2005

Purpose

To examine the relationship between myofiber disarray and myocardial hypokinesis in human hypertrophic cardiomyopathy (HCM) using noninvasive cardiac diffusion and strain MRI.

Materials and Methods

Five patients with a diagnosis of HCM and five age‐matched healthy volunteers were studied and compared. Cardiac diffusion MRI was applied to map in vivo myocardial fiber architecture. Cardiac strain MRI was applied to map myocardial motion. By acquiring registered diffusion and strain MRI images in vivo on both normal and HCM hearts, we investigated in HCM the relationship between myofiber disarray and systolic strain components, including radial, fiber, and cross‐fiber strains, and sought to determine the mechanism behind disarray‐related myocardial dysfunction in HCM.

Results

Regionally disordered fiber orientation and reduced diffusion fractional anisotropy (FA) were found in HCM, demonstrating myofiber disarray. Intramural myocardial strain hypokinesis (reduced radial, fiber, and cross‐fiber strains) was also observed in HCM in the same region, and was found to be correlated with FA. The correlation between FA and hypokinesis was found to be stronger in the cross‐fiber direction (part of the passive myocardial function) compared to the fiber direction (part of the active myocardial function). This is consistent with the hypothesis that the principal feature of HCM is the reduction of myocardium passive compliance. The angle between principal shortening and fiber orientation was markedly disordered in HCM, indicating an abnormal transmural coupling.

Conclusion

Myofiber disarray in HCM is correlated with abnormalities of both passive and active myocardial function, and the normal patterns of fiber shortening and wall thickening are deranged in HCM. J. Magn. Reson. Imaging 2006. © 2005 Wiley‐Liss, Inc.
Entanglement induced by the two-mode thermal noise
Authors: Bashkirov E K
Published: December 2005

The entanglement between two identical two-level atoms interacting with a two-mode thermal field through a nondegenerate two-photon process is investigated. It is shown that two atoms can be entangled through a nonlinear nondegenerate two-photon interaction with two-mode thermal field. On the contrary, for the two-atom Raman coupled model the entanglement is impossible.
Preparation of silver nanoparticles by laser ablation and
fragmentation in pure water
Authors: Hajiesmaeilbaigi F , Mohammadalipour A , Sabbaghzadeh J , Hoseinkhani S , Fallah H R
Published: December 2005

Silver nanoparticles were produced by irradiating a
silver plate with 1064 nm laser beam in pure water. The effect of
the laser fluence and ablation time on the ablation efficiency was
studied. Fragmentation of the ablated colloid solution by
subsequent treatment with 1064 and 532 nm laser pulses yield
redistribution of nanoparticles to a smaller mean size.
Chemistry of Siloxane Amide as a New Curing Agent for Epoxy Resins: Material Characterization and Properties
Authors: Srividhya Marimuthu , Lakshmi Madurai Suguna , Reddy Boreddy Sivarami R.
Published: December 2005

Summary: A novel amine terminated elastomeric siloxane modifier (SA amine) for epoxy networks has been synthesized and characterized. The dual role of SA amine not only as a curing agent and but also as a toughener was studied. Curing studies of conventionally available epoxy resin, diglycidyl ether of bisphenol A (DGEBA) using SA amine along with diamino diphenyl sulfone (DDS) has been carried out. An interesting feature was the complete miscibility of the siloxane oligomer with DGEBA. In addition, the cured laminates were analyzed for thermal, mechanical, and surface morphology and also for their chemical resistance. The thermo mechanical properties were studied using dynamic mechanical analysis. The modified systems showed very high thermal stability. A single glass transition temperature was observed for the modified systems. The moisture resistance of the samples improved notably with the introduction of siloxane into the systems. The modified systems also improved the impact strength of the materials to a greater extent (35–50%) even though there was a small decrease in their tensile properties (12%). The system with maximum SA amine content showed the higher impact strength value and also a higher thermal stability without any phase separation in the morphology.

Representation of the crosslinking pattern of the resin systems.

magnified image

Representation of the crosslinking pattern of the resin systems.
Selective Removal of Dilute Benzene from Water by Various Cross‐Linked Poly(dimethylsiloxane) Membranes Containing tert‐Butylcalix[4]arene
Authors: Ohshima Tadahiro , Miyata Takashi , Uragami Tadashi
Published: December 2005

Summary: This paper focuses on the addition of tert‐butylcalix[4]arene (CA) to cross‐linked poly(dimethylsiloxane) (PDMS) membranes derived from poly(dimethylsiloxane) di(methyl methacrylate) macromonomer (PDMSDMMA) and various divinyl cross‐linker compounds, on the pervaporation characteristics for the removal of dilute benzene from an aqueous solution. When an aqueous solution of 0.05 wt.‐% benzene was permeated through the cross‐linked PDMSDMMA membranes containing CA they showed high benzene/water selectivity and permeability. Both the benzene/water selectivity and permeability of the membranes were enhanced by increasing both the divinyl compound cross‐linker content and the amount of CA, and were significantly influenced by the type of divinyl compound. Addition of CA to PDMSDMMA membranes cross‐linked with divinylperfluorohexane (DVF) showed the best pervaporation performance. The normalized permeation rate, benzene/water separation factor, and pervaporation separation index of these membranes were 1.86 × 10−5 kg · m/(m2 · h), 5 027, and 9 350, respectively. The pervaporation characteristics of the cross‐linked PDMSDMMA membranes containing CA were studied with respect to their chemical and physical structure. Furthermore, the mechanism of the selective permeation of benzene over water through these membranes was investigated.

magnified image
Novel Metal‐Containing Polyurethane Elastomers Prepared Using Tetradentate Schiff Base Metal Complexes
Authors: Senthilkumar Natarajan , Raghavan A. , Nasar A. Sultan
Published: December 2005

Summary: A series of divalent metal (Co2+, Ni2+, Cu2+)‐incorporated tetradentate Schiff base complexes of the generic name 1,2‐bis[{4‐(2‐hydroxy)ethoxy‐2‐hydroxyphenyl}methyl ketimino]ethane‐metal(II) (BHEHPMKE‐M)—metal‐containing dihydroxy monomers—were synthesized and characterized by UV‐visible, FT‐IR, MS, and atomic absorption spectroscopies and elemental analysis. Structure of one of the monomers was also confirmed by single‐crystal X‐ray diffraction technique. Several metal‐containing polyurethanes were prepared using these dihydroxy compounds and 1,4‐butanediol as chain extenders for prepolymers based on poly(oxytetramethylene) glycol‐2000 (PTMG‐2000) and 4,4′‐methylene bis(phenyl isocyanate) (MDI). The amount of metal‐containing monomer was varied from 0 to 1 equivalent to find the influence of the metal‐incorporated tetradentate Schiff base segment on thermal and mechanical properties of polyurethanes. The properties of metal‐containing polyurethanes were compared with those prepared using 1,4‐butanediol and 1,2‐bis[{4‐(2‐hydroxy)ethoxy phenyl}methyl ketimino]ethane—a diol without metal—as chain extenders. The polymers were characterized by FT‐IR, GPC, DSC, TGA, viscosity, and solubility measurements. The glass transition temperature (Tg) of the polyurethane prepared from the Schiff base diol (without metal) was found to increase when used alone as chain extender. Thermal and mechanical properties of polyurethanes were also found to improve markedly by the introduction of metal‐incorporated tetradentate Schiff base moiety into the polymer chain. The viscosity of the metal‐containing polyurethane decreased abruptly upon increasing the metal content.

A series of polyurethanes derived from novel divalent metal (Co2+, Ni2+, Cu2+)‐incorporated tetradentate Schiff base complexes.

magnified image

A series of polyurethanes derived from novel divalent metal (Co2+, Ni2+, Cu2+)‐incorporated tetradentate Schiff base complexes.
Nanoporous SiLK® Dielectric Films Prepared from Free‐Radical Graft Polymerization and Thermolysis
Authors: Chen Yiwang , Chen Lie , Wang Xiaofeng , He Xiaohui
Published: December 2005

Summary: Thermally‐initiated free‐radical graft polymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA) with the ozone‐pretreated SiLK® precursor was carried out. The chemical composition and structure of the graft copolymers were characterized by NMR and X‐ray photoelectron spectroscopy (XPS). Nanoporous low dielectric constant (κ) SiLK films were prepared by solution spin‐casting of the graft copolymers on the Si(100) substrates, followed by thermally‐induced cycloaddition and cross‐linking of the SiLK precursor and thermal decomposition of the labile PEGMA side chains. The nanoporous SiLK films so‐obtained had well‐preserved SiLK backbones and pore size in the range of 10–15 nm. The refractive index (RI) of resulting films has decreased to 1.47, from 1.62 for the pristine (non‐porous) SiLK dielectric film. A dielectric constant of about 2.2 was achieved from thermolysis of the SiLK graft copolymer containing about 15.2 wt.‐% of the PEGMA side chains.

Preparation of the nanoporous SiLK dielectric film.

magnified image

Preparation of the nanoporous SiLK dielectric film.
Preparation of Fluorescent Carboxyl and Amino Functionalized Polystyrene Particles by Miniemulsion Polymerization as Markers for Cells
Authors: Holzapfel Verena , Musyanovych Anna , Landfester Katharina , Lorenz Myriam Ricarda , Mailänder Volker
Published: December 2005

Summary: A series of fluorescent polystyrene latex particles with carboxyl and amino functionalities on their surface were synthesized by the miniemulsion technique. The fluorescent dye N‐(2,6‐diisopropylphenyl)perylene‐3,4‐dicarboximide (PMI) was incorporated into the copolymer nanoparticles formulated from styrene and acrylic acid or styrene and aminoethyl methacrylate hydrochloride. The resulting latexes were stable and showed a monodisperse size distribution. The particle size depended on the amount and nature of the functional comonomer and was in the range 100–175 nm. All latexes were characterized by transmission electron microscopy (TEM), dynamic light scattering, UV‐Vis spectroscopy and zeta potential measurements. The amount of surface functional groups was determined by electrolyte titration. Furthermore, the functionalized fluorescent particles were utilized as markers for HeLa cells and cell uptake was visualized using fluorescence microscopy. The correlation of the uptake of nanoparticles with the surface charge was determined by FACS measurements.

Confocal fluorescent microscopy of HeLa cells after the uptake of amino functionalized particles (green).

magnified image

Confocal fluorescent microscopy of HeLa cells after the uptake of amino functionalized particles (green).
Organic Montmorillonite as a Substitute for Aerosilica in Addition‐Type Liquid Silicone Rubber Systems
Authors: Wang Jincheng , Chen Yuehui , Jin Qiqi
Published: December 2005

Summary: A novel addition‐type liquid silicone rubber (SR)/organic montmorillonite (OMMT) nanocomposite has been synthesized. N,N‐Di(2‐hydroxyethyl)‐N‐dodecyl‐N‐methylammonium chloride was used as an intercalation agent to treat Na+‐montmorillonite and form a novel kind of OMMT. Three types of SR/OMMT composites were synthesized with different amounts of OMMT, and were compared with an aerosilica‐modified SR system. Tensile strength, and other properties determined by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), were compared. A combination of Fourier‐transform infrared (FT‐IR) spectroscopy, wide‐angle X‐ray diffraction (WAXD), scanning electron microscopy (SEM), and transmission electronic microscopy (TEM) studies showed that SR/OMMT composites were on the nanometer scale, and the segmented structure of the SR was disrupted by the presence of OMMT, as a result of the reaction between the monomer and the intercalation agent. Results showed that the physical and mechanical properties of an SR system with 1 phr of OMMT were nearly equal to that of an SR system with 3 phr of aerosilica because of the exfoliation of the OMMT and the resultant nano‐effect in the system.

WAXD spectra of the organic montmorillonite (OMMT)‐intercalated silicone rubber

magnified image

WAXD spectra of the organic montmorillonite (OMMT)‐intercalated silicone rubber
Aliphatic Hyperbranched Copolyesters by Combination of ROP and AB2‐Polycondensation
Authors: Smet Mario , Gottschalk Carsten , Skaria Sunny , Frey Holger
Published: December 2005

Summary: Hyperbranched aliphatic copolyesters have been prepared by the copolymerization of ε‐caprolactone and 2,2‐bis(hydroxymethyl)butyric acid (AB2‐monomer), catalyzed by (i) HfCl4(THF)2 and (ii) diphenylammonium trifluoromethanesulfonate (DPAT), respectively. In both cases, copolymerization by combined ROP/AB2‐polycondensation was achieved. The degree of branching (DB) and consequently the density of functional groups of the resulting copolyesters were controlled by the comonomer ratio in the feed. Molecular weights in the range $\overline M _{\rm n}$ = 22 000–166 000 g · mol−1 (GPC, PS standards) were obtained, with apparent polydispersity indices of 1.20 to 1.95. The DB was in the range 0.03–0.35. Remarkably, HfCl4(THF)2 appeared to cause no transesterification of the ester bonds in the hyperbranched polymer formed. Further esterification or functionalization of the hydroxyl end groups of the hyperbranched polymers is therefore possible in a convenient two step/one pot process. The prepared hyperbranched polycaprolactones can be used as multifunctional initiators for the ROP of ε‐caprolactone, which is also catalyzed by HfCl4(THF)2, resulting in multi‐arm star polymers. Diphenylammonium trifluoromethanesulfonate (DPAT) was also found to catalyze the combination of ROP and AB2 polycondensation. However, the applicability of this system is restricted due to side reactions that can lead to crosslinking.

Synthesis of hyperbranched copolyesters by combined ROP/polycondensation.

magnified image

Synthesis of hyperbranched copolyesters by combined ROP/polycondensation.
Dissipative Particle Dynamics Simulation of Microphase Separation and Properties of Linear–Dendritic Diblock Copolymer Melts under Steady Shear Flow
Authors: Liu Dahuan , Zhong Chongli
Published: December 2005

Summary:Dissipative particle dynamic simulations were performed on the microphase separation, end‐to‐end distance, and shear viscosity of linear–dendritic diblock copolymers under steady shear flow. The results show that their microstructure and properties depend on both the shear rate and the degree of branching, and they can incorporate the characteristics of both linear and dendritic polymers to lead to new materials with unique properties.

Schematic structure for the linear‐dendritic copolymer G4 described in this work.

image

Schematic structure for the linear‐dendritic copolymer G4 described in this work.