bluuebunny/crossref_metadata_2025 huggingface dataset:
Endometrial cancer cell survival and apoptosis is regulated by protein kinase C α and δ
Authors: Haughian James M , Jackson Twila A , Koterwas David M , Bradford Andrew P
Published: December 2006

Endometrial cancer is the most common invasive gynecologic malignancy but the molecular mechanisms underlying its onset and progression are poorly understood. Paradoxically, endometrial tumors exhibit increased apoptosis, correlating with disease progression and poor patient prognosis. Endometrial tumors also show altered activity and expression of protein kinase C (PKC) isoforms, implicated in the regulation of programmed cell death; however, PKC modulation of apoptosis in endometrial cancer cells has not been investigated. We detected nine out of ten PKC isoforms in Ishikawa endometrial cancer cell lines, and demonstrated expression of both PKCα and δ in human endometrial tumors. To determine the functional roles of PKCα and δ in apoptosis in endometrial cancer, Ishikawa cells were treated with selective PKC inhibitors or adenoviral constructs encoding wild-type or isoform-specific, dominant-negative mutants. Apoptosis was assessed by DNA fragmentation and caspase-mediated poly-(ADP-ribose)-polymerase cleavage. The inhibition of PKCδ suppressed etoposide-induced apoptosis, while overexpression of PKCδ enhanced it. In contrast, inhibition of PKCα elevated basal levels of apoptosis and potentiated etoposide-induced cell death. Etoposide treatment also selectively activated PKCδ, but resulted in both cytosolic translocation and decreased activity of PKCα. A fraction of PKCδ also underwent caspase-dependent cleavage, in response to etoposide. Our results suggest that changes in apoptosis and PKC expression in endometrial cancer are mechanistically linked, such that PKCδ is required for DNA damage-induced apoptosis, while PKCα mediates a survival response. Thus, PKCα and δ expression and signaling may be important in endometrial tumorigenesis and could serve as potential prognostic indicators and/or novel targets for therapeutic intervention.
Gene expression profiling in insulinomas of Men1 β-cell mutant mice reveals early genetic and epigenetic events involved in pancreatic β-cell tumorigenesis
Authors: Fontanière S , Tost J , Wierinckx A , Lachuer J , Lu J , Hussein N , Busato F , Gut I , Wang Z-Q , Zhang C-X
Published: December 2006

Mutations of the MEN1 gene lead to the occurrence of multiple endocrine neoplasia type 1 (MEN1). To gain insights into the mechanisms of the tumorigenesis related to MEN1 inactivation, we have used mice in which the Men1 gene was specifically disrupted in pancreatic β-cells. In these mice, we observed full penetrance of insulinoma with defined histological characteristics of tumorigenesis. To identify the genetic factors taking part in the tumour development, we performed gene expression profiling analysis of these insulinomas at different stages. Here, we show that in late stage insulinomas, 56 genes are up-regulated and 194 are down-regulated more than fourfold compared with normal pancreatic islets. Clustering analysis reveals the deregulation of Hox gene family and the genes involved in cell proliferation and cell cycle control. The altered expression of Igf2, Igfbp3 and Igfbp6 as well as cyclin A2, B2 and D2 are confirmed by quantitative RT-PCR, with the overexpression of all the three cyclins found in early stage insulinomas. Moreover, an increased proportion of cyclin A2- and D2-expressing cells and the overexpression of insulin-like growth factor 2 (IGF2) protein are detected in mouse Men1 insulinomas by immunostaining. Interestingly, the analysis of DNA methylation patterns by quantitative serial pyrosequencing reveals that four specific CpGs in the intragenic differentially methylated region 2 (DMR2) region of the Igf2 gene known to augment transcription through methylation are significantly hypermethylated in insulinomas of Men1 β-cell mutant mice at 6 and 10 months of age, even before IGF2 overexpression can be detected. Thus, our data indicate the involvement of both genetic and epigenetic mechanisms in early tumorigenesis of β-cells related to MEN1 inactivation.
Local and regional control in patients with papillary thyroid carcinoma: specific indications of external radiotherapy and radioactive iodine according to T and N categories in AJCC 6th edition
Authors: Chow Sin-Ming , Yau Stephen , Kwan Chung-Kong , Poon Patricia C M , Law Stephen C K
Published: December 2006

To identify indications for external radiotherapy (EXT) and radioactive iodine (RAI) in papillary thyroid carcinoma (PTC), we conducted a retrospective study of local and regional control in 1297 patients diagnosed with PTC in a tertiary referral center. Managed by surgery alone, patients with bilateral thyroidectomy had a lower rate of local relapse compared with lobectomy (P = 0.02). EXT improved locoregional (LR) failure-free survival (FFS) (P < 0.001) and survival (P = 0.01) in patients with gross postoperative LR residual disease. EXT also improved local FFS in patients with pathologically confirmed positive resection margins (P < 0.001) and reduced local failures in patients with T4 disease (P = 0.002). In patients with lymph nodes (LN) metastasis, more extensive surgery by functional or radical neck dissection resulted in less LN relapse compared with excision alone (P < 0.001). EXT improved 10-year LN FFS in patients with N1b disease (P = 0.005) and patients with LN metastasis of size > 2 cm (P = 0.02). RAI was effective in improving local control in patients with T2 to T4 diseases and LN control in patients with N0, N1a, and N1b categories. Local or LN relapses were associated with worse survival (P < 0.001 and P < 0.0001). The survival of patients with PTC could be improved by reducing local or LN relapses. RAI is indicated in patients with T2 to T4 disease. EXT is indicated in patients with gross postoperative disease, positive resection margins or T4 disease, N1b, or a LN size of > 2 cm. LN relapse can be reduced by RAI in N0, N1a, and N1b disease.
Straight privilege and moral/izing: Issues in career development
Authors: Rocco Tonette S. , Gallagher Suzanne J.
Published: December 2006

This chapter deconstructs heterosexual privilege in the workplace and offers suggestions for “queering the workplace” with an emphasis on career development.
Lesbians: Identifying, facing, and navigating the double bind of sexual orientation and gender in organizational settings
Authors: Gedro Julie
Published: December 2006

This chapter explores the challenges and the opportunities that lesbians experience in organizational America.
Geometric morphometric study of population variation in indigenous southern African crania
Authors: Franklin D. , Freedman L. , Milne N. , Oxnard C.E.
Published: December 2006

Much of our understanding of population variation in southern Africa is derived from traditional morphometric research. In the search for new perspectives, this paper reports on new geometric morphometric data examining cranial variation in 12 modern human populations from southern Africa. In total, 298 male Bantu‐speaking individuals were studied. In addition, a small Khoisan (Khoikhoi and San) series was also examined. The purpose of this study was to investigate Khoisan‐Bantu morphological similarities and differences, and to examine variation within both the Bantu‐speaking and Khoisan populations. The three‐dimensional coordinates of 96 landmarks were analyzed, using the shape‐analysis software morphologika. Interpopulation variation was examined by calculating Procrustes distances between groups; a cluster analysis was then used to summarize phenetic relationships. A principal components analysis explored the relationships between populations; shape differences were visualized and explored using three‐dimensional rendered models, and further interpreted using thin‐plate splines. Morphological differences are present within and between the crania of Bantu‐speaking and Khoisan individuals. The Khoisan demonstrate features (e.g., a pentagonoid vault, more rounded forehead contour, and a small and less prognathic face) that clearly distinguish them from Bantu‐speaking populations. Although southern African Bantu‐speaking populations are clearly closely related, they show population‐specific features (e.g., the crania of more southerly populations (Xhosa, Southern Sotho, and Zulu) are characteristically more brachycephalic and less prognathic). This study suggests that differential admixture with adjacent Khoisan peoples has contributed to diversity within southern African Bantu‐speaking populations. Am. J. Hum. Biol. 19:20–33, 2007. © 2006 Wiley‐Liss, Inc.
Factor analysis of risk variables associated with metabolic syndrome in Asian Indian adolescents
Authors: Ghosh Arnab
Published: December 2006

The purpose of the present cross‐sectional study was to identify components of risk variables associated with metabolic syndrome in Asian Indian adolescents. The sample included 400 adolescents (boys = 200; mean age, 15.0 ± 4.5 years; girls = 200; mean age, 14.4 ± 3.8 years) from Calcutta, India. The following variables were considered: body mass index, waist circumference, sum of four skinfolds, subscapular/triceps ratio, total cholesterol, triglycerides, blood glucose, and systolic, diastolic, and mean arterial pressure. Principal component factor analysis revealed four uncorrelated factors for adolescent boys that cumulatively explained 76.3% of the observed variance of metabolic syndrome. Four factors with overlap between factors 1 and 2 were observed for adolescent girls that cumulatively explained 74.3% of the total variation of metabolic syndrome. The four factors identified were central body fat distribution (factor 1), centralized subcutaneous fat (factor 2), lipids‐blood glucose (factor 3), and blood pressure (factor 4). Furthermore, the first two factors, i.e., central body fat distribution and centralized subcutaneous fat, cumulatively explained more than 46% (46.5% for boys; 46.4% for girls) of the observed variation of metabolic syndrome. Since more than one factor was identified for metabolic syndrome, more than one physiological mechanism could account for the clustering of risk variables of metabolic syndrome in Asian Indian adolescents. Factor analysis of Asian Indian adults also revealed four uncorrelated factors, similar to the present factors, therefore warranting intervention as early as adolescence. Am. J. Hum. Biol. 19:34–40, 2007. © 2006 Wiley‐Liss, Inc.
Attention deficit/hyperactivity disorder (ADHD) symptoms and digit ratios in a college sample
Authors: Stevenson J.C. , Everson P.M. , Williams D.C. , Hipskind G. , Grimes M. , Mahoney E.R.
Published: December 2006

Diagnosticians recognize three subtypes of attention deficit/hyperactivity disorder (ADHD) if there are developmentally inappropriate levels (six or more symptoms) of Hyperactive‐Impulsive behavior, or Inattentive behavior, or both (Combined), respectively. ADHD may partly reflect androgen dysfunction, and an arguable proxy for prenatal androgen exposure is the 2D:4D finger ratio set at least as early as week 9 in the fetus; this is lower in men than in women. We examined the relationship between digit ratios and ADHD symptoms representing the three phenotypes: ADHD/Combined as measured by “summarized” (Rasched) scales, i.e., 1) the short version of the Wender Utah Rating Scale (WURS) and a total symptom list derived from the DSM IV, and the subdivided DSM IV into 2) ADHD/Inattentive and 3) ADHD/Hyperactive‐Impulsive inventories, in a sample of European‐descent college students (135 female, 52 male) not selected for ADHD. All digit ratios were calculated excluding the thumb. There were significant sex differences for the 2D:4D digit ratios of both hands (RH and LH), and between the RH 3D:4D and between the LH 2D:3D ratio. In females, the more masculine the LH 2D:4D ratio, the more the ADHD/Combined symptoms (both WURS and DSM) and the more the ADHD/Inattentive symptoms and ADHD/Hyperactive‐Impulsive symptoms. More masculine ratios also correlated between the total WURS and RH 2D:3D, RH 2D:4D, and LH 2D:3D; and between the inattentive DSM symptoms and LH 2D:5D, and between the ADHD/Hyperactive and Impulsive symptoms and RH 3D:4D. Am. J. Hum. Biol. 19:41–50, 2007. © 2006 Wiley‐Liss, Inc.
Growth and health status of street children in Dhaka, Bangladesh
Authors: Greksa Lawrence P. , Rie Naganuma , Islam A.B.M. Rafiqul , Maki Uchida , Omori Kinuko
Published: December 2006

The purpose of this study was to assess the effect of street life on the growth and health status of poor children who live and work full‐time on the streets of Dhaka, Bangladesh (street children), independent of the effects of poverty. This was accomplished by comparing 142 street children with 150 poor children who live and work on the streets of Dhaka but who return to their families at night (slum children). Children between 7–14 years old were recruited at locales where street and slum children are typically found. Weight and upper arm circumference did not differ significantly between street and slum children (P > 0.05), but energy reserves, as assessed by skinfolds, were significantly larger in street than in slum children (P < 0.05). There was no wasting in either street or slum children. Although the majority of children in both groups were stunted and underweight, there were no significant differences between groups (P > 0.05). The prevalence of disease symptoms tended to be slightly higher in street children than in slum children, but few of the differences were statistically significant (P < 0.05). These data do not support the contention that street children are a particularly high‐risk group. The greater‐than‐expected growth and health status of street children, compared to other poor children, may be due to biologically fitter children being more likely to permanently move to the streets and/or to remain on the streets once the move has been made. Am. J. Hum. Biol. 19:51–60, 2007. © 2006 Wiley‐Liss, Inc.
Fatness and overweight in women and children from riverine Amerindian communities of the Beni River (Bolivian Amazon)
Authors: Benefice Eric , Lopez Ronald , Monroy Selma Luna , Rodríguez Sonia
Published: December 2006

Obesity is a worldwide public health problem impacting not only industrialized nations but also developing countries. The main objective of this paper was to analyze risk factors for overweight among Amerindian children and their mothers. Data were collected in 15 Amerindian riverside communities from the Beni River (Bolivia). The total sample was of 195 mothers and 452 children, 0–15 years of age. Information about family activity and dietary patterns was collected, and a clinical examination was performed. Stool samples were collected in children for parasitological screening. Anthropometric measurements, including weight, height, arm circumference, and four skinfolds, were taken. A bioelectrical impedance analysis was performed in mothers. In total, 12.2% (95% confidence interval (CI95%) 9.1–15.9%) of the children were considered overweight; less than 1% were overtly obese International Obesity Task Force (IOTF) criteria. Among their mothers, 35.3% (CI95%, 28.7–42.5%) were overweight (BMI (weight/height 2) >25 kg/m2), and 5% (CI95%, 2.5–5.1%) were obese (BMI >30 kg/m2). BMI was moderately related to anthropometric indices of body composition in children, but was highly correlated with fatness in mothers. The risk of overweight was not associated with environmental factors in children. In mothers, there was a significant relationship between BMI, health status, and dietary diversity score. There was a moderate association in boys between fatness and the BMI of their mothers (R2 = 0.12, P < 0.001), but not in girls. These findings suggest a trend toward accumulation of fat related to possible changes at the economic and agricultural levels, even in remote rural areas. Am. J. Hum. Biol. 19:61–73, 2007. © 2006 Wiley‐Liss, Inc.
Repeatability and interobserver error of digit ratio (2D:4D) measurements made by experts
Authors: Voracek Martin , Manning John T. , Dressler Stefan G.
Published: December 2006

The second‐to‐fourth digit ratio (2D:4D) is sexually differentiated (lower in men than in women), a likely biomarker for organizational (permanent) effects of prenatal testosterone, and a correlate of many sex‐dependent, hormonally influenced traits and phenotypes. The extent of 2D:4D measurement repeatability across different research groups is unknown. This study assessed the repeatability and interobserver error of 2D:4D measurements made by 17 experts (researchers who have contributed to the 2D:4D literature). Results indicate that 2D:4D, because it is a ratio variable, is notably less precisely measurable than finger length. Absolute‐agreement intraclass correlation coefficients for these traits are about 0.75 vs. about 0.95, respectively. Associations of 2D:4D with target traits were usually of small size; measurement unreliability attenuates effects. This may explain some null findings and replication failures encountered in 2D:4D research. However, agreement levels are still sufficient to permit conclusions about findings from different research groups. One implication of this is that the marked geographical and population differences in typical 2D:4D levels, as reported in the literature, are veridical, and not due to divergent measurement habits across research groups. Some practical recommendations for 2D:4D measurement are offered. Am. J. Hum. Biol. 19:142–146, 2007. © 2006 Wiley‐Liss, Inc.
Early life events and their consequences for later disease: A life history and evolutionary perspective
Authors: Gluckman Peter D. , Hanson Mark A. , Beedle Alan S.
Published: December 2006

Biomedical science has little considered the relevance of life history theory and evolutionary and ecological developmental biology to clinical medicine. However, the observations that early life influences can alter later disease risk—the “developmental origins of health and disease” (DOHaD) paradigm—have led to a recognition that these perspectives can inform our understanding of human biology. We propose that the DOHaD phenomenon can be considered as a subset of the broader processes of developmental plasticity by which organisms adapt to their environment during their life course. Such adaptive processes allow genotypic variation to be preserved through transient environmental changes. Cues for plasticity operate particularly during early development; they may affect a single organ or system, but generally they induce integrated adjustments in the mature phenotype, a process underpinned by epigenetic mechanisms and influenced by prediction of the mature environment. In mammals, an adverse intrauterine environment results in an integrated suite of responses, suggesting the involvement of a few key regulatory genes, that resets the developmental trajectory in expectation of poor postnatal conditions. Mismatch between the anticipated and the actual mature environment exposes the organism to risk of adverse consequences—the greater the mismatch, the greater the risk. For humans, prediction is inaccurate for many individuals because of changes in the postnatal environment toward energy‐dense nutrition and low energy expenditure, contributing to the epidemic of chronic noncommunicable disease. This view of human disease from the perspectives of life history biology and evolutionary theory offers new approaches to prevention, diagnosis and intervention. Am. J. Hum. Biol. 19:1–19, 2007. © 2006 Wiley‐Liss, Inc. © 2006 Wiley‐Liss, Inc.
Anthropometric data indicate nutritional homogeneity in Hadza foragers of Tanzania
Authors: Sherry Diana S. , Marlowe Frank W.
Published: December 2006

We analyzed body mass index (BMI = wt/height2) and percent body fat (BF%) in adults of the Hadza, an egalitarian society with a strong food‐sharing ethic, to examine variation in energetic status in relation to sex, age, and time of year. Data collected from 26 camps over six field seasons gave a cross‐sectional sample of 238 males and 235 females and a small longitudinal sample (n = 54). We found that mean BMI showed no sex difference [20.1 ± 1.6 (SD) kg/m2 for males and 20.3 ± 2.2 kg/m2 for females] and remained similar, regardless of age or time of year. Mean BF% showed a significant sex difference, as expected [10.6 ± 3.2 (SD) % for males and 19.0 ± 7.0% for females (P < 0.0001)], with two significant age departures from uniformity: (1) males in the prime age group (30–45 years, n = 79) had a higher mean BF% (11.7%) compared to other ages (P < 0.03), and (2) females in the extreme elderly age group (> 75 years, n = 11) had a lower mean BF% (11.3%) compared to other ages (P < 0.004). In the longitudinal sample, we found no significant change over time in mean BMI or BF%. However, relative change in BF% fluctuated within individuals by as much as 20% of initial values for both sexes. Taken collectively, our results support the idea of broad nutritional homogeneity among the Hadza, but indicate that subtle, potentially important differences in energetic condition exist as well. Am. J. Hum. Biol. 19:107–118, 2007. © 2006 Wiley‐Liss, Inc.
Biological divergence and equality during the first millennium BC in human populations of central Italy
Authors: Rubini Mauro , Mogliazza Silvia , Corruccini Robert Spencer T.
Published: December 2006

The frequencies of nine discrete cranial traits are contrasted among 10 skeletal series of central Italy to assess the patterning of biological affinity or divergence. In this study various statistical applications were used: Mean Measure of Divergence (MMD), which was elaborated using the WPGMA cluster analysis, neighbor‐joining method and principal coordinate analysis. The results show two main groups divided by the Apennines, which probably were a geographic barrier to biological exchange during the Italian Iron Age. This fact induced endogamous phenomena in the populations on the two sides of Italy (Adriatic and Tyrrenian) and probably increased the familial segregation of traits. The group on the western side has a further division between samples of the central coast and those of the southern coast. The latter samples seem to be more closely connected to Sardinian peoples, and this indicates gene flow and cultural contacts, which were not hindered by the sea. This segregation appears to have receded by Roman times. Am. J. Hum. Biol. 19:119–131, 2007. © 2006 Wiley‐Liss, Inc.
Production of ϵ‐poly‐L‐lysine by newly isolated Kitasatospora sp. PL6‐3
Authors: Ouyang Jia , Xu Hong , Li Sha , Zhu Hongyang , Chen Weiwei , Zhou Jun , Wu Qun , Xu Lin , Ouyang Pingkai
Published: December 2006

A novel ϵ‐poly‐L‐lysine (ϵ‐PL)‐producing strain PL6‐3 was isolated from soil, and was identified as a strain of Kitasatospora sp. This is the first detailed report of production of ϵ‐PL by a strain in the genera of Kitasatospora. By controlling the culture pH at 4.0, the yield of ϵ‐PL from PL6‐3 reached 13.9 g/L after 120 h of cultivation in fed‐batch fermentation. The morphological characteristics of Kitasatospora sp. PL6‐3 in culture broth were different from those reported from strains of Streptomycetaceae, as no mycelium pellets were observed during the course of fermentation of PL6‐3, which was beneficial to the assimilation of nutrition and secretion of the products. Furthermore, the molecular mass of the purified ϵ‐PL from PL6‐3 was determined to be 5.01 kDa by SDS‐PAGE and 5.05 kDa by gel permeation chromatography, indicating that the ϵ‐PL produced by this strain might be composed of 40 lysine residues. Usually, ϵ‐PL with more lysine residues showed higher antimicrobial activity; however, it was difficult to obtain ϵ‐PL with more than 36 lysine residues in this study. As a result, ϵ‐PL from Kitasatospora sp. PL6‐3, which contains more lysine residues than that from other strains, is more promising in the field of food preservatives.
Investigation and molecular mimicry of the antigen involved in the interaction between the monoclonal antibody 5D10 and the human breast cancer cell line MCF‐7
Authors: Vandevyver Caroline , Canarelli Stéphane , Bossen Claudia , Fisch Igor , Motmans Kris , Raus Jef , Freitag Ruth
Published: December 2006

Monoclonal antibody (mAb) 5D10 is directed against the human breast cancer cell line MCF‐7. Biochemical characterization of the antibody epitope was attempted and revealed a complex, most likely carbohydrate‐linked nature, which prevented isolation and further studies of the interaction. A major goal of this work was to generate structural mimics of the 5D10 epitope to serve as putative substitutes in such studies. A peptide library displayed on filamentous phage was used to select for mimotope peptide sequences. All positive phage clones selected from the library displayed the amino acid sequence H2NQMNPMYYRCO2H. This peptide sequence, as well as a branched form of the peptide, was found to bind mAb 5D10. Moreover, both peptide sequences were able to inhibit the binding of 5D10 to the MCF‐7 cells in a concentration‐dependent manner, with an EC50 value in the range of 65 µM. According to these results, random phage peptide libraries can serve to identify mimotopic peptides for unknown complex cell surface epitopes. Biotechnol. Bioeng. 2007;97: 721–734. © 2006 Wiley Periodicals, Inc.
Transhepatic vascular access for diagnostic and interventional procedures: Techniques, outcome, and complications
Authors: Ebeid Makram R.
Published: December 2006

Early or multiple cardiac catheterizations may result in occlusion of the femoral veins prohibiting their use. The internal jugular or sub‐clavian approach may be an appropriate alternative. However, these approaches may not be suitable in patients with surgical interruption of the superior vena cava. In other patients, they may not allow easy access to certain areas of the heart. The transhepatic approach is an important alternative route for performing cardiac catheterization and interventions. Depending on the planned procedure, it may be the preferred route to perform the cardiac catheterization even in the presence of patent femoral veins. The indications, technical details and potential complications of this approach are discussed. © 2006 Wiley‐Liss, Inc.
Ring‐Opening Cross‐Metathesis (ROCM) as a Novel Tool for the Ligation of Peptides
Authors: Michaelis Simon , Blechert Siegfried
Published: December 2006

The development of ring‐opening cross‐metathesis (ROCM) as a novel tool for the site‐specific ligation of peptide units is reported. The resulting structural units at the site of ligation resulting from ROCM resemble proline as well as other known β‐turn stabilising structural units. ROCM under mild reaction conditions between a variety of peptides bearing a cyclic olefin with amino acids or peptides results in high yields. The peptidic cross‐partners for metathesis are equipped with double bonds via the N and the C terminus and the side chain, respectively, to allow the synthesis of linear as well as non‐linear and branched peptides. The ligation in this manner succeeds with low catalyst loadings, with no need for any excess of one reaction partner and with a high compatibility with a wide range of functional groups. Furthermore, the stereochemical outcome of the ROCM can easily be controlled by using a Hoveyda‐type chiral catalyst. Fluorescence labelling of peptides is possible in the same manner when using a cyclic olefin equipped with a fluorescence marker.
Structural and Dynamic Characterization of Copper(II) Binding of the Human Prion Protein Outside the Octarepeat Region
Authors: Berti Francesco , Gaggelli Elena , Guerrini Remo , Janicka Anna , Kozlowski Henryk , Legowska Anna , Miecznikowska Hanna , Migliorini Caterina , Pogni Rebecca , Remelli Maurizio , Rolka Krzysztof , Valensin Daniela , Valensin Gianni
Published: December 2006

Human prion protein (hPrP) fragments encompassing the 91–120 region, namely hPrP92–100 (SP1), hPrP106–113 (SP2), hPrP91–120 (LP1), and hPrP91–114 (LP2), were considered for delineation of the CuII‐binding site(s). NMR and EPR spectroscopy results obtained from LP1 or LP2 were compared with those obtained from SP1 and SP2. The coexistence of two binding sites, one centered at His96 and the other at His111, was evidenced and ratified by ESI mass spectrometry at low and high metal:peptide ratios. While room‐temperature NMR spectroscopy data were consistent with the binding site centered on His111 being approximately fourfold stronger than that centered on His96, low‐temperature EPR spectroscopy results yielded evidence for the opposite trend. This disagreement, which has also occurred in the literature, was clarified by temperature‐dependent molecular dynamics runs that demonstrated Met112 approaching the metal at room temperature, a process that is expected to stabilize the His111‐centered binding site through hydrophobic shielding of the metal coordination sphere.
Randomized, placebo‐controlled trial of Saforis for prevention and treatment of oral mucositis in breast cancer patients receiving anthracycline‐based chemotherapy
Authors: Peterson Douglas E. , Jones James B. , Petit Robert G.
Published: December 2006

BACKGROUND.

Oral mucositis (OM) is a frequent complication of mucotoxic cancer therapy, causing significant oral pain, increased infection risk, and impaired functioning. The efficacy and safety of Saforis (glutamine) powder in UpTec for oral suspension was evaluated for the prevention and treatment of OM.

METHODS.

Three hundred twenty‐six patients developing World Health Organization (WHO) grade ≥2 OM during a chemotherapy screening cycle were randomized to Saforis (n = 163) or placebo (n = 163) 3 times/day during their next chemotherapy cycle (Treatment Cycle 1). Patients were crossed over to the alternate treatment during Treatment Cycle 2. As prespecified in the statistical plan, because of a carryover effect in Treatment Cycle 2 the primary efficacy analysis was based on Treatment Cycle 1 only.

RESULTS.

Compared with placebo, Saforis significantly reduced the incidence of clinically significant WHO grade ≥2 OM (38.7% vs. 49.7%; P = .026) and severe WHO grade ≥3 OM (1.2% vs. 6.7%; P = .005) in Treatment Cycle 1. Saforis also significantly reduced the worst Oral Mucositis Assessment Scale ulceration score in Treatment Cycle 1 compared with placebo (mean, 0.23 ± 0.39 vs. 0.32 ± 0.45; P = .013). Patients receiving Saforis in Treatment Cycle 1 had a lower‐than‐expected OM incidence when crossed over to placebo in Treatment Cycle 2, indicating a significant carryover effect (P = .027). The incidence of treatment‐emergent adverse events was similar between groups.

CONCLUSIONS.

Saforis is safe and effective for preventing and treating OM in patients receiving mucotoxic cancer chemotherapy. Cancer 2007. © 2006 American Cancer Society.
Predictive and discriminating three‐risk‐group prognostic scoring system for staging Hodgkin lymphomas
Authors: Maucort‐Boulch Delphine , Djeridane Malika , Roy Pascal , Riche Benjamin , Colonna Pierre , Andrieu Jean‐Marie
Published: December 2006

BACKGROUND.

Several 3‐stage Ann Arbor classification‐derived prognostic systems were constructed since 1980 to identify the prognosis of Hodgkin lymphoma (HL). Modern statistical tools were applied to 955 patients treated between 1981 and 1996 to build a 3‐stage prognostic scoring system (PSS).

METHODS.

Each variable associated with 10‐year overall survival (10‐year OS) was assigned to 2 (0 or 1) or 3 (0, 1 or 3) values. By summing the values attributed to each variable, 3 stages were defined. 10‐year OS, 5‐year event‐free survival (5‐year EFS), and freedom from progression (5‐year FFP) rates of the PSS and of other existing systems were then compared.

RESULTS.

Four variables were associated with 10‐year OS: age (<40 = 0, ≥40 = 1), number of involved lymphoid areas (1–2 = 0, 3–4 = 1, ≥5 = 2), visceral disease (no = 0, yes = 1), and systemic symptoms (no = 0, yes = 1). Scores 0 and 1, 2 and 3, and ≥4 were attributed to 59.7%, 30.9%, and 9.4% of the patients who had 10‐year OS rates of 93.5, 75.7, and 53.4% and 5‐year EFS / 5‐year FFP rates of 91.2%/90.3%, 78.1%/76.3%, and 54.1%/52.6%, respectively. The discrimination and prediction abilities of the PSS were better than those of the other systems tested; moreover, the PSS adequately identified the few patients with a worse prognosis without resorting to the International Prognostic Score for advanced stages. The PSS was also highly predictive for 489 patients treated between 1997 and 2002.

CONCLUSION.

PSS is a useful alternative to the existing prognostic systems for evaluating HL patients. Cancer 2007. © 2006 American Cancer Society.
Clinical course of nonvisceral soft tissue leiomyosarcoma in 225 patients from the Scandinavian Sarcoma Group
Authors: Svarvar Catarina , Böhling Tom , Berlin Örjan , Gustafson Pelle , Follerås Gunnar , Bjerkehagen Bodil , Domanski Henryk A. , Sundby Hall Kirsten , Tukiainen Erkki , Blomqvist Carl ,   and the Scandinavian Sarcoma Group Leiomyosarcoma Working Group
Published: December 2006

BACKGROUND.

Leiomyosarcoma of nonvisceral soft tissues is an uncommon malignant tumor; thus, only small numbers of cases have been reported. This study was based on a large series of patients from the Scandinavian Sarcoma Group Register acquired during a 15‐year period (from 1986 to 2001). Follow‐up information was available for all patients.

METHODS.

The authors analyzed the clinical features of 225 patients with cutaneous, subcutaneous, or deep‐seated leiomyosarcoma of the extremities, trunk wall, and superficial parts of the head and neck region to determine the natural course of the disease. Only patients who received their treatment at a specialist sarcoma center were included. Re‐evaluation of histopathology was performed.

RESULTS.

The age of the patients (121 women and 104 men) ranged from 20 years to 98 years (median, 70 years), and the tumors ranged in size from 0.6 cm to 35 cm (median, 4.0 cm). Eighty‐two percent of the tumors were classified as high grade. The median follow‐up for survivors was 5.5 years. The local treatment was adequate in 154 of 206 patients (75%) who were without metastasis at presentation. At 10 years, 84% of the 206 patients with localized disease at presentation were free from local recurrence, 66% remained metastasis free, and 49% were alive. Multivariate analysis showed that higher malignancy grade (P = .006), larger tumor size (P = .003), and deeper tumor location (P = .002) were correlated significantly with decreased metastasis‐free survival, inadequate local treatment was correlated with local recurrence (P = .007), and high malignancy grade was correlated with decreased overall survival (P = .007).

CONCLUSIONS.

The long‐term prognosis for patients with subcutaneous and deep‐seated soft tissue leiomyosarcoma remains poor despite the ability to achieve adequate local control through nonmutilating surgery with or without radiotherapy. Cancer 2007. © 2006 American Cancer Society.
Effect of routine follow‐up after treatment for laryngeal cancer on life expectancy and mortality
Authors: Ritoe Savitri C. , de Vegt Femmie , Scheike Inger M. , Krabbe Paul F. M. , Kaanders Johannes H. A. M. , van den Hoogen Frank J. A. , Verbeek André L. M. , Marres Henri A. M.
Published: December 2006

BACKGROUND.

Routine follow‐up is offered to all patients with laryngeal cancer who are treated with curative intent. Although time and resources are devoted to surveillance, the effect of asymptomatic recurrence detection is not well understood. For this study, the authors evaluated the effect that routine follow‐up may have on life expectancy and disease‐specific mortality rate for patients with laryngeal cancer.

METHODS.

Using a Markov model, a cohort simulation was performed on 4 hypothetical age groups of patients with laryngeal cancer. Three different follow‐up strategies were compared—the current schedule, no follow‐up, and the perfect follow‐up—in which all recurrences were detected asymptomatically. Sensitivity analyses were performed to study the impact of variations in the transition rates on life expectancy.

RESULTS.

Compared with no follow‐up, the current schedule showed a gain in life expectancy with a range from 0.3 years to 1.5 years that decreased with advancing age. Abolishing the current follow‐up schedule raised the disease‐specific mortality rate; the increase ranged from 2.8% to 5.9%. Variations of ±25% in the transition rates produced only a modest effect on life expectancy.

CONCLUSIONS.

A small reduction in life expectancy was observed when follow‐up was withheld from the majority of patients. Disease‐specific mortality rates rose when no follow‐up was provided. These rates probably were overestimated. A simplified version of the current follow‐up protocol may be implemented. Cancer 2007. © 2006 American Cancer Society.
Magnitude and laterality of breast cancer risk according to histologic type of atypical hyperplasia
Authors: Collins Laura C. , Baer Heather J. , Tamimi Rulla M. , Connolly James L. , Colditz Graham A. , Schnitt Stuart J.
Published: December 2006

BACKGROUND.

Atypical hyperplasia (AH) in a benign breast biopsy is associated with an increased breast cancer risk. However, the influence of the histologic type of AH on the magnitude and laterality of breast cancer risk is poorly defined.

METHODS.

The authors conducted a case‐control study of benign breast disease and breast cancer risk nested within the Nurses' Health Study (395 cases, 1610 controls). Benign breast biopsy slides were reviewed and categorized as showing nonproliferative lesions, proliferative lesions without atypia, or AH. Slides that showed AH were categorized further as atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH).

RESULTS.

The odds ratio (OR) for breast cancer among all women with AH was 4.1 (95% confidence interval [95% CI], 2.9–5.8). However, among premenopausal women, breast cancer risk was higher for women with ALH (OR, 7.3; 95% CI, 3.8–14.2) than for women with ADH (OR, 3.1; 95% CI, 2.0–4.8). Overall, 58.9% of invasive breast cancers that developed in women with AH were in the ipsilateral breast, and the frequency of ipsilateral breast cancer was similar for women with ALH (61.3%) and women with ADH (55.9%; P = .66).

CONCLUSIONS.

Women with AH in a benign breast biopsy were at a substantially increased risk for the development of breast cancer. Among premenopausal women, the risk appeared to be greater for those with ALH than those with ADH. Because only ≈60% of cancers that develop in women with AH occur in the ipsilateral breast, for the purposes of clinical management, these lesions are viewed best as markers of a generalized (bilateral) increase in breast cancer risk. Cancer 2007. © 2006 American Cancer Society.
Neural network model for solving integral equation of acoustic scattering using wavelet basis
Authors: Hesham M. , El‐Gamal M. A.
Published: December 2006

In this work, neural networks (NNs) are trained in order to obtain a fast and efficient solution of the integral equation of acoustic scattering. Wavelets sparsification methods are utilized to reduce the NN size and complexity. The non‐uniqueness problem which arises in solving this integral equation at characteristic frequencies can, also, be solved using such network without any additional computational load. Experimental results show excellent agreement between the NN‐based solution and the analytical solution of a spherical scatterer. Copyright © 2006 John Wiley & Sons, Ltd.
Analysis of symmetric structures using canonical forms
Authors: Kaveh A. , Salimbahrami B.
Published: December 2006

Canonical forms are recently employed in eigenproblems of structural mechanics to calculate the eigenvalues and eigenvectors. In this paper, such applications are extended to the static analysis of symmetric structures. In classical approaches the structure is decomposed into substructures and appropriate boundary conditions are then imposed. Here, a systematic method is developed which does not operate directly on the structural model, but rather on the matrices involved in the analysis of the structures. Copyright © 2006 John Wiley & Sons, Ltd.
Electric‐Field‐Driven Deracemization
Authors: Kane Alexander , Shao Ren‐Fan , Maclennan Joseph E. , Wang Lixing , Walba David M. , Clark Noel A.
Published: December 2006

We demonstrate, both theoretically and experimentally, that it is possible to use an electric field to drive the formation of macroscopic chiral (conglomerate) domains from an initially homogeneous fluid racemate. Field‐induced segregation is exhibited in a fluid smectic liquid‐crystal phase of a racemic mesogen, wherein enantiomerically‐enriched domains are readily identifiable by their chiral electro‐optical response. The sharp field‐generated boundaries that form between opposite‐handed domains broaden by diffusion in the absence of field, but reform rapidly if the field is switched on again, providing unambiguous evidence for the field‐driven physical separation of enantiomers. A mean‐field model successfully describes the steady‐state and the dynamic evolution of conglomerate formation.
Existence condition of state equations of linear active networks over F(z)
Authors: Lu Kai‐Sheng
Published: December 2006

If the physical parameter of each branch of a linear active network is considered to be an independently variable parameter, then it is called a network over the field F(z) of all rational functions in its physical parameters. This paper discusses the existence condition of state equation over F(z) for the active network. The condition depends only on the network structure, and is applied to two examples, which shows that the method is straightforward. Copyright © 2006 John Wiley & Sons, Ltd.
A New Target for Highly Stereoselective Katsuki–Sharpless Epoxidation – One‐Pot Synthesis of C2‐Symmetric 2,2′‐Bioxiranes
Authors: Bilenko Vitaliy , Jiao Haijun , Spannenberg Anke , Fischer Christine , Reinke Helmut , Kösters Jutta , Komarov Igor , Börner Armin
Published: December 2006

The double asymmetric Katsuki–Sharpless epoxidation of a conjugated diallyl alcohol affords excellent enantioselectivity (>97 % ee), the product being isolated as the stable p‐nitrobenzoate 5a or tosylate 5b. The optical purities of the chiral epoxides were determined by HPLC on chiral columns, while the molecular structures of compounds 5a and 7 and the absolute configuration of mono‐epoxide 12 were confirmed by X‐ray crystallography. Possible π–π stacking interaction has been evaluated by ab initio calculation.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Spatial Imaging of Cu2+‐Ion Release by Combining Alternating Current and Underpotential Stripping Mode Scanning Electrochemical Microscopy
Authors: Ruhlig Dirk , Schuhmann Wolfgang
Published: December 2006

Anodic underpotential stripping voltammetry was integrated into SECM in order to characterize local corrosion of metallic copper deposits on metal surfaces as a model for copper containing alloys. Primarily, the alternating current mode of SECM was applied in an electrolyte of low ionic strength for localizing possible corrosion sites without any perturbation of the corroding surface, e.g., by the presence of any redox mediator. Sequentially, the release of Cu2+‐ions was confirmed and locally visualized at the previously detected electrochemically active sites by means of spatially resolved anodic underpotential stripping voltammetry performed during SECM scanning. Underpotential stripping voltammetry of Cu2+‐ions was performed at a specifically developed 15 μm gold‐coated Pt microelectrode used as SECM tip with a detection limit of 0.15 nM Cu2+ (N=4, RSD=6%) for an accumulation of 45 s at −0.4 V. SECM images of model samples such as copper coated microelectrodes and lacquered metallic copper workpieces demonstrated the feasibility and applicability of combining AC‐ and underpotential stripping mode of SECM for local visualization of Cu2+‐ion release from corroding surfaces.
EOF measurement by detection of a sampling zone with end‐channel amperometry in microchip CE
Authors: Wang Wei , Zhao Liang , Jiang Li‐Ping , Zhang Jian‐Rong , Zhu Jun‐Jie , Chen Hong‐Yuan
Published: December 2006

A simple method for EOF measurement by detection of sampling zones with end‐channel amperometry in microchip CE is developed. This method is based on the principle of the Kohlrausch regulating function (KRF). A dilute electroactive ionic species is added to the BGE as a continuously eluting electrophore which is used as a probe. When a BGE‐like sample at a different concentration is injected, a peak of sampling zone appears and the migration time is related to EOF. In a microchip CE with hybrid PDMS/glass channel, a cathodic EOF of the hybrid glass/PDMS microchip was measured by end‐channel amperometry; the effects of sample concentration and different probes on EOF rate were discussed. The present method was applied to monitor EOF rates in glass and in PDMS microchips. There was no significant difference between the values of EOF rates measured by the present method and the current‐monitoring method. Detection of nonelectroactive analytes K+, Na+, and Li+ can also be accomplished by the indirect amperometric method. Hence, the effective mobility of analyte can be accurately obtained.
A fast and reliable route integrating calibration and analysis protocols for water‐soluble vitamin determination on microchip‐electrochemistry platforms
Authors: Crevillén Agustín González , Blasco Antonio Javier , González María Cristina , Escarpa Alberto
Published: December 2006

A novel analytical route to determine water‐soluble vitamins (B group and C) using single channel microchip‐electrochemistry platforms is presented. The electrochemical detection protocol was carefully optimized, and it was shown that it was crucial to use 1 M nitric acid in the detector compartment to detect folic acid. A phosphate buffer (pH 6, 10 mM) and a separation voltage of 2 kV gave the complete separation of vitamins in less than 130 s, with good reproducibility (RSDs less than 10%) and accuracy (error less than 9%). In addition, a methodological innovation integrating calibration and analysis of water‐soluble vitamins on the chip is also proposed. The strategy consisted in sequentially using both reservoirs (named calibration and analysis reservoirs) as well as a calibration factor (defined as signal/concentration of analyte). The analytical route required 350 s in the overall protocol (employing 130 s in calibration plus 130 s in analysis), an improvement over the times used in both conventional and microchip protocols.
Binge eating tendencies and anger coping: investigating the confound of trait neuroticism in a non‐clinical sample
Authors: Connolly Anne M. , Rieger Elizabeth , Caterson Ian
Published: December 2006

Objective

Binge eating has been found to be associated with anger suppression. However, the anger suppression measure used in previous research is highly saturated with trait neuroticism. Furthermore, the dichotomised view of anger coping as either ‘in’ or ‘out’ has been questioned. The present study investigated the influence of trait neuroticism on the relationship between binge eating and anger suppression. In addition, a broader measure of anger coping was utilised.

Method

One hundred forty non‐clinical women completed measures of binge eating, anger coping and trait neuroticism.

Results

Anger suppression, rumination and a lack of assertion (i.e. anger inexpressiveness) were significantly correlated with binge eating tendencies. However, hierarchical regression analyses showed that the anger inexpressiveness measures were not predictive of binge eating tendencies over and above trait neuroticism. Furthermore, the association between anger inexpressiveness and binge eating tendencies was differentially affected by the separate facets of neuroticism.

Discussion

Results suggest that the relationship between anger inexpressiveness and binge eating tendencies is partially accounted for by the impulsiveness and depressive affect facets of neuroticism. Previous studies are questioned in light of these findings and areas for further research are considered. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association.