bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetic Studies Prove High Catalytic Activity of a Diene–Rhodium Complex in 1,4‐Addition of Phenylboronic Acid to α,β‐Unsaturated Ketones
Authors: Kina Asato , Yasuhara Yuichi , Nishimura Takahiro , Iwamura Hiroshi , Hayashi Tamio
Published: November 2006

In the 1,4‐addition of phenylboronic acid to α,β‐unsaturated ketones, [Rh(OH)(cod)]2 has a much higher catalytic activity than [Rh(OH)(binap)]2 (cod=1,5‐cyclooctadiene, binap=2,2′‐bis(diphenylphosphanyl)‐1,1′‐binaphthyl). Kinetic studies revealed that the rate‐determining transmetalation step in the catalytic cycle has a large rate constant when [Rh(OH)(cod)]2 is used.
Ion exchange chromatography of antibody fragments
Authors: Ljunglöf Anders , Lacki Karol M. , Mueller Jay , Harinarayan Chithkala , van Reis Robert , Fahrner Robert , Van Alstine James M.
Published: November 2006

Effects of pH and conductivity on the ion exchange chromatographic purification of an antigen‐binding antibody fragment (Fab) of pI 8.0 were investigated. Normal sulfopropyl (SP) group modified agarose particles (SP Sepharose™ Fast Flow) and dextran modified particles (SP Sepharose XL) were studied. Chromatographic measurements including adsorption isotherms and dynamic breakthrough binding capacities, were complemented with laser scanning confocal microscopy. As expected static equilibrium and dynamic binding capacities were generally reduced by increasing mobile phase conductivity (1–25 mS/cm). However at pH 4 on SP Sepharose XL, Fab dynamic binding capacity increased from 130 to 160 (mg/mL media) as mobile phase conductivity changed from 1 to 5 mS/cm. Decreasing protein net charge by increasing pH from 4 to 5 at 1.3 mS/cm caused dynamic binding capacity to increase from 130 to 180 mg/mL. Confocal scanning laser microscopy studies indicate such increases were due to faster intra‐particle mass transport and hence greater utilization of the media's available binding capacity. Such results are in agreement with recent studies related to ion exchange of whole antibody molecules under similar conditions. Biotechnol. Bioeng. 2007;96: 515–524. © 2006 Wiley Periodicals, Inc.
A water activity control system for enzymatic reactions in organic media
Authors: Petersson Anna E.V. , Adlercreutz Patrick , Mattiasson Bo
Published: November 2006

A water activity control system for enzymatic synthesis in organic media, for litre‐scale reactors has been constructed. Water activity, aw, is a key factor when using enzymes in non‐conventional media and the optimum value varies for different enzymes. The control system consists of a water activity sensor in the headspace of a jacketed glass reactor (equipped with narrow steel tubes to introduce air), gas‐washing bottles containing blue silica gel (aw = 0) and water (aw = 1), a PC to monitor water activity and a programmable logic controller (PLC) to control the water activity. The system was evaluated by adjusting water activity in the medium, with a deviation from the set point of less than ±0.05. Synthesis of cetyl palmitate, under controlled water activity and catalysed by two different lipase preparations, namely, Novozym® 435 (immobilised Candida antarctica lipase B) and immobilised Candida rugosa lipase, were also performed. Novozym® 435 catalyses reactions very well at extremely low water activity while C. rugosa lipase shows low activity for aw < 0.5. Biotechnol. Bioeng. 2007;97: 235–241. © 2006 Wiley Periodicals, Inc.
Clinicopathological significance of microscopic abscess formation at the invasive margin of advanced low rectal cancer
Authors: Uehara K , Nakanishi Y , Shimoda T , Taniguchi H , Akasu T , Moriya Y
Published: November 2006

Background

The aim of this study was to evaluate the clinicopathological significance of microscopic abscess formation (MAF) at the invasive front of advanced low rectal cancer.

Methods

The clinicopathological features of 226 consecutive patients with low rectal cancer, who underwent curative resection between May 1997 and December 2002, were analysed.

Results

Fifty-seven (25·2 per cent) of the 226 tumours had MAF and 169 (74·8 per cent) did not. Patients with tumours showing MAF were more likely to have extended surgery than those without MAF: 47 versus 31·4 per cent respectively underwent non-sphincter-preserving surgery (P = 0·029) and 82 versus 60·9 per cent underwent lateral lymph node dissection (P = 0·003). The incidence of lymph node metastases was lower in patients with MAF (30 versus 53·3 per cent; P = 0·002). Univariable analysis of disease-free survival revealed that depth of invasion (P < 0·001), lymph node status (P < 0·001), histological type (P = 0·035), lymphatic invasion (P < 0·001), venous invasion (P < 0·001), perineural invasion (P < 0·001), focal dedifferentiation (P < 0·001) and MAF (P < 0·001) were significant prognostic factors. Multivariable analysis showed that lymph node status (P < 0·001), perineural invasion (P = 0·002), venous invasion (P = 0·033) and MAF (P = 0·012) remained independent prognostic factors.

Conclusion

MAF may reflect indolent tumour behaviour and a more favourable outcome in patients with advanced low rectal cancer.
Carl Friedrich Naumann and the introduction of enantio terminology: A review and analysis on the 150th anniversary
Authors: Gal Joseph
Published: November 2006

Enantiomorphism and enantiomorphous were the first enantio‐based terms, introduced 150 years ago, by Carl Friedrich Naumann, a German crystallographer, to refer to non‐superposable mirror‐image crystals. The terminology was not adopted by Pasteur, the discoverer of molecular chirality, and was not embraced at first in the stereochemical context, until it was accepted in 1877 by Van 't Hoff in the German edition of his proposal for the tetrahedral asymmetric carbon atom. In the 1890s the use of enantio terms began to spread in the research literature, and many new derivatives of Naumann's original two terms were subsequently introduced. Problems in the usage of some of the terms are often found in the literature, e.g., enantiomorphism is sometimes confused with chirality; enantiomeric is often misused; the meaning of some of the many derived terms, e.g., enantiosymmetric, enantioposition, etc., is unclear. All in all, Naumann should be remembered as the creator of essential terminology in the realm of chirality. Chirality, 2006. © 2006 Wiley‐Liss, Inc.
Organic Molecular Beam Deposition of Oligophenyls on Au(111): A Study by X‐ray Absorption Spectroscopy
Authors: Müllegger Stefan , Hänel Kathrin , Strunskus Thomas , Wöll Christof , Winkler Adolf
Published: November 2006

Near‐edge X‐ray absorption fine structure (NEXAFS) spectroscopy has been applied to reveal the molecular arrangement of ultrathin oligophenyl films [p‐quaterphenyl (4P) and p‐hexaphenyl (6P)] on Au(111). In the half‐monolayer films the molecules lie flat on the surface but still have a considerable inter‐ring twist of 30°‐40°, similar to the gas‐phase conformation. In the saturated monolayer film the second half of the molecules is side‐tilted by an angle of less than 66° with respect to the surface. This arrangement is already similar to that in bulk net planes of thicker films parallel to the surface, that is, the 4P(211) and 6P(21‐3) planes, respectively.
Noggin signaling from Xenopus animal blastomere lineages promotes a neural fate in neighboring vegetal blastomere lineages
Authors: Huang Sen , Yan Bo , Sullivan Steven A. , Moody Sally A.
Published: November 2006

In Xenopus, localized factors begin to regionalize embryonic fates prior to the inductive interactions that occur during gastrulation. We previously reported that an animal‐to‐vegetal signal that occurs prior to gastrulation promotes primary spinal neuron fate in vegetal equatorial (C‐tier) blastomere lineages. Herein we demonstrate that maternal mRNA encoding noggin is enriched in animal tiers and at low concentrations in the C‐tier, suggesting that the neural fates of C‐tier blastomeres may be responsive to early signaling from their neighboring cells. In support of this hypothesis, experimental alteration of the levels of Noggin from animal equatorial (B‐tier) or BMP4 from vegetal (D‐tier) blastomeres significantly affects the numbers of primary spinal neurons derived from their neighboring C‐tier blastomeres. These effects are duplicated in blastomere explants isolated at cleavage stages and cultured in the absence of gastrulation interactions. Co‐culture with animal blastomeres enhanced the expression of zygotic neural markers in C‐tier blastomere explants, whereas co‐culture with vegetal blastomeres repressed them. The expression of these markers in C‐tier explants was promoted when Noggin was transiently added to the culture during cleavage/morula stages, and repressed with the transient addition of BMP4. Reduction of Noggin translation in B‐tier blastomeres by antisense morpholino oligonucleotides significantly reduced the efficacy of neural marker induction in C‐tier explants. These experiments indicate that early anti‐BMP signaling from the animal hemisphere recruits vegetal equatorial cells into the neural precursor pool prior to interactions that occur during gastrulation. Developmental Dynamics 236:171–183, 2007. © 2006 Wiley‐Liss, Inc.
GATA‐4 is required for sex steroidogenic cell development in the fetal mouse
Authors: Bielinska Malgorzata , Seehra Amrita , Toppari Jorma , Heikinheimo Markku , Wilson David B.
Published: November 2006

The transcription factor GATA‐4 is expressed in Sertoli cells, steroidogenic Leydig cells, and other testicular somatic cells. Previous studies have established that interaction between GATA‐4 and its cofactor FOG‐2 is necessary for proper Sry expression and all subsequent steps in testicular organogenesis, including testis cord formation and differentiation of both Sertoli and fetal Leydig cells. Since fetal Leydig cell differentiation depends on Sertoli cell–derived factors, it has remained unclear whether GATA‐4 has a cell autonomous role in Leydig cell development. We used two experimental systems to explore the role of GATA‐4 in the ontogeny of testicular steroidogenic cells. First, chimeric mice were generated by injection of Gata4−/− ES cells into Rosa26 blastocysts. Analysis of the resultant chimeras showed that in developing testis Gata4−/− cells can contribute to fetal germ cells and interstitial fibroblasts but not fetal Leydig cells. Second, wild‐type or Gata4−/− ES cells were injected into the flanks of intact or gonadectomized nude mice and the resultant teratomas examined for expression of steroidogenic markers. Wild‐type but not Gata4−/− ES cells were capable of differentiating into gonadal‐type steroidogenic lineages in teratomas grown in gonadectomized mice. In chimeric teratomas derived from mixtures of GFP‐tagged Gata4+/+ ES cells and unlabeled Gata4−/− ES cells, sex steroidogenic cell differentiation was restricted to GFP‐expressing cells. Collectively these data suggest that GATA‐4 plays an integral role in the development of testicular steroidogenic cells. Developmental Dynamics 236:203–213, 2007. © 2006 Wiley‐Liss, Inc.
The contribution of phonological awareness and visual attention in early reading and spelling
Authors: Plaza Monique , Cohen Henri
Published: November 2006

We examined the development of phonological processing, naming speed, and visual attention in kindergarten and addressed the question of their contribution to reading and spelling in grade 1. Seventy five French‐speaking children were administered seven tasks at the two phases of the study, and reading and spelling were assessed in grade 1. The major findings revealed that syllable awareness and visual attention were the most important predictors of early reading and spelling, and confirm the influence of naming speed and phoneme awareness on specific skills. These observations strongly suggest that written language acquisition relies on linguistic, perceptual and cognitive cross‐modal skills and highlight the need for diversifying written language measures and analyzing their specific predictors. Copyright © 2006 John Wiley & Sons, Ltd.
Three Novel Functional CdII Dicarboxylates with Nanometer Channels: Hydrothermal Synthesis, Crystal Structures, and Luminescence Properties
Authors: Tian Yu‐Peng , Zhu Yong‐Min , Zhou Hong‐Ping , Wang Peng , Wu Jie‐Ying , Tao Xu‐Tang , Jiang Min‐Hua
Published: November 2006

Three novel functional transition‐metal complexes with H2A (H2A = 9‐ethylcarbazole‐3,6‐dicarboxylic acid), Cd(HA)2(H2O)2 (1), [Cd(A)(phen)]·1.5H2O (2) (phen = 1,10‐phenanthroline), and Cd(HA)2(bipy) (3) (bipy = 4,4′‐bipyridine), have been successfully synthesized by a hydrothermal synthetic method and characterized by single‐crystal X‐ray diffraction, infrared spectroscopy, elemental analysis, thermogravimetric analysis, and photoluminescence. The results show that all of the complexes contain nanometer channels, while the coordination modes were changed by the addition of the mixed ligands. The 2D supramolecular open‐framework 1 is constructed through hydrogen‐bond and aromatic π–π interactions. 2D coordination polymer 2 is constructed by π–π interactions between adjacent metal‐organic polymeric coordination chains. Interestingly, the 3D supramolecular architecture of 3 first formed 2D grid layers from 1D chains by intermolecular hydrogen bonds and then extended into a 3D structure through aromatic π–π interactions. Furthermore, strong emissions from these complexes were also changed by the coordination modes in the solid state. However, complexes 1–3 show high thermal stability.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Stereochemical Control of Chirally Flexible Phosphepines
Authors: Zalubovskis Raivis , Fjellander Ester , Szabó Zoltán , Moberg Christina
Published: November 2006

The barriers to interconversion of the two enantiomeric atropisomers of 6‐methoxy‐6,7‐dihydro‐5H‐dibenzo[c,e]phosphepine and that of the diastereomeric forms of 6‐(–)‐menthoxy‐6,7‐dihydro‐3H‐dibenzo[c,e]phosphepine were determined by NMR spectroscopical methods to be 19.3 and 18.5 kcal mol–1, respectively, at 298 K. The ratio of the atropisomers was shown to depend on the group bound to phosphorus. Only complexes with two homochiral ligands bound to the each metal center were obtained upon reaction with [Rh(COD)2]+ BF4–. The Rh complexes catalyzed the hydrogenation of α‐acetamidocinnamate. The major isomer of6‐(–)‐menthoxy‐6,7‐dihydro‐5H‐dibenzo[c,e]phosphepinewas found to exhibit higher activity but to afford a product with lower ee than its diastereomer. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Use of micromolded carbon dual electrodes with a palladium decoupler for amperometric detection in microchip electrophoresis
Authors: Mecker Laura C. , Martin R. Scott
Published: November 2006

The fabrication and evaluation of micromolded dual carbon ink electrodes and their integration with a fabricated palladium decoupler for use in microchip electrophoresis is described. As opposed to previous work involving carbon‐based dual electrodes with microchip electrophoresis, this approach results in electrodes that are amenable to mass production in a manner where the decoupler/electrode alignment is fixed and reproducible. In this work, electrode sizes and spacings were optimized to result in dual carbon electrodes that are 1 µm in height and separated by 100 µm. Fluorescence microscopy was used to investigate leakage around the electrode/channel interface as well as to investigate what effect the dual electrodes have on band broadening phenomena. The performance of the microelectrodes was demonstrated by the separation and selective dual electrode detection of neurotransmitters in the presence of ascorbic acid. It was also found that addition of SDS to the buffer system improved both the LODs and collection efficiencies. This approach, which is the first involving carbon‐based dual electrodes with an on‐chip palladium decoupler, will be useful for separating and detecting neurotransmitters that are either collected by in vivo sampling or released from cells on‐chip.
Kommunikation im Netz der Information
Authors: Hesse Friedrich W. , Buder Jürgen , Bauer Korinna
Published: November 2006

Wie kann der Wissensaustausch in Computernetzen sinnvoll unterstützt werden? Neue Studien geben Einblick in die Chancen und Risiken netzbasierter Kommunikation in Gruppen, deren Gelingen nicht nur vom Medium abhängt
„Karrieren”︁im Termitenstaat
Authors: Korb Judith
Published: November 2006

Trockenholztermiten können Arbeiter bleiben oder Königin werden. Ihre Kolonien werden von einem besonderen Zusammenleben geprägt, was das landläufige Bild von sozialen Insekten und ihrem Verhalten erweitert
Unique regulation of long term potentiation in the rat ventral hippocampus
Authors: Maggio Nicola , Segal Menahem
Published: November 2006

Morphological and electrophysiological evidence has been accumulated in recent years to indicate that a functional gradient exists along the septo‐temporal axis of the hippocampus such that spatial memory is associated primarily with the dorsal (septal) sector while the functions of the ventral sector are not yet clearly defined. Also, the ventral hippocampus (VH) is reported to express a much smaller long term potentiation of responses to afferent stimulation than the dorsal sector. In the present study, we first confirmed that CA1 region of VH slices expresses significantly smaller LTP than the dorsal hippocampus. Strikingly, much larger LTP was obtained in VH slices following low frequency priming stimulation applied prior to the tetanic stimulation. DHPG ((S)‐3,5‐Dihydroxyphenylglycine hydrate) a metabotropic glutamate receptor agonist, produced a similar potentiating effect on LTP as that produced by the priming stimulation. In both cases, the spectral analysis of spontaneous electrical activity recorded from the same location in the slice revealed an increase in peak amplitude around 30 Hz. MCPG, a metabotropic glutamate receptor antagonist, and both thapsigargin and cyclopiazonic acid, inhibitors of Ca2+ release from stores, blocked the potentiating action of both DHPG and the priming stimulation. These results indicate that the ventral hippocampus possesses different network properties compared to the dorsal hippocampus and that its ability to undergo plastic changes is controlled by a metabotropic glutamate receptor. © 2006 Wiley‐Liss, Inc.
Occupational exposure to organochlorine insecticides and cancer incidence in the Agricultural Health Study
Authors: Purdue Mark P. , Hoppin Jane A. , Blair Aaron , Dosemeci Mustafa , Alavanja Michael C.R.
Published: November 2006

Organochlorine (OC) insecticides have been regulated as possible human carcinogens primarily on the basis of animal studies. However, the epidemiologic evidence is inconsistent. We investigated the relationship between cancer incidence and OC insecticide use among pesticide applicators enrolled in the Agricultural Health Study, a prospective cohort study of 57,311 licensed applicators in Iowa and North Carolina enrolled between 1993 and 1997. Information on ever use of 7 OC insecticides (aldrin, chlordane, DDT, dieldrin, heptachlor, lindane, toxaphene) was collected from a self‐administered questionnaire at enrollment. Lifetime exposure‐days to OC insecticides were calculated using additional data from a take‐home questionnaire completed by 25,291 participants (44% of total). We found no clear evidence of an association between use of OC insecticides and incident cancers (N = 1,150) ascertained through December, 2002. When we focused on individual insecticides and structurally similar groups (aldrin and dieldrin; chlordane and heptachlor), significantly increased relative risks of some cancers were observed for use of some chemicals (rectal cancer and chlordane, lung cancer and dieldrin, non‐Hodgkin lymphoma (NHL) and lindane, melanoma and toxaphene, leukemia and chlordane/heptachlor). Some significant decreased relative risks were also observed (colon cancer and aldrin; overall cancer and heptachlor). In conclusion, we did not observe any clear relationship between cancer risk and the use of OC insecticides. Our chemical‐specific findings are based on small numbers and multiple comparisons, and should be interpreted with caution; however, some observed associations (lindane and NHL, chlordane/heptachlor and leukemia) are supported by previous evidence. © 2006 Wiley‐Liss, Inc.
Identification of an HLA‐A24‐restricted cytotoxic T lymphocyte epitope from human papillomavirus type‐16 E6: The combined effects of bortezomib and interferon‐γ on the presentation of a cryptic epitope
Authors: Morishima Satoko , Akatsuka Yoshiki , Nawa Akihiro , Kondo Eisei , Kiyono Tohru , Torikai Hiroki , Nakanishi Toru , Ito Yoshinori , Tsujimura Kunio , Iwata Kosuke , Ito Koji , Kodera Yoshihisa , Morishima Yasuo , Kuzushima Kiyotaka , Takahashi Toshitada
Published: November 2006

About 50% of cervical cancers are associated with human papillomavirus type 16 (HPV‐16), and since the HPV‐16 E6 and E7 oncoproteins are constitutively expressed in the tumor cells, they are attractive targets for cytotoxic T lymphocyte (CTL)‐mediated immunotherapy. Nevertheless, only a limited number of HPV‐16 E6 epitopes have been identified to date. Using reverse immunological methods, we have generated a CTL clone against the HPV‐16 E649–57 epitope restricted by HLA‐A*2402, which is the most common allele in Japan and relatively frequent worldwide, capable of lysing 293T cells transduced with HLA‐A*2402 and HPV‐16 E6. Although it was unable to recognize the SiHa cervical cancer cell line positive for HPV‐16 and HLA‐A*2402, the cells became susceptible to lysis when transduced with E6‐E7 genes, which was unexpectedly offset by pretreatment with interferon (IFN)‐γ alone. Interestingly, however, combined pretreatment with a proteasome inhibitor, bortezomib and IFN‐γ fully restored CTL‐mediated lysis of the original SiHa cells. Furthermore, such intervention of 2 of 4 other cervical cancer cell lines expressing HPV‐16 E6 and HLA‐A*2402 was found to induce IFN‐γ production by specific CTLs. Tetramer analysis further revealed that induction of E649–57‐specific T cells was possible in 5 of 7 patients with HPV‐16‐positive high grade cervical intraepithelial neoplasia or cervical cancer by in vitro stimulation with E649–57 peptide. Thus, these findings together indicate that E649–57 is a candidate epitope for immunotherapy and immunological monitoring of such patients. © 2006 Wiley‐Liss, Inc.
Risk of cervical cancer associated with Chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors
Authors: Madeleine Margaret M. , Anttila Tarja , Schwartz Stephen M. , Saikku Pekka , Leinonen Maija , Carter Joseph J. , Wurscher Michelle , Johnson Lisa G. , Galloway Denise A. , Daling Janet R.
Published: November 2006

Human papillomavirus (HPV) is the central etiologic factor for cervical cancer, and prior studies suggested C. trachomatis may act as an HPV cofactor. We examined the C. trachomatis‐cervical cancer association by serotype, histology, HPV type in the tumor, and other HPV cofactors. We conducted a population‐based study in the Seattle‐Puget Sound area of 302 women with invasive squamous cell carcinomas (SCC), 185 women with adenocarcinomas of the cervix (AC), and 318 HPV seropositive control women. The risk of SCC associated with antibodies to C. trachomatis was increased (OR 1.6, 95% CI 1.1–2.2) but not for AC (OR 1.0, 95% CI 0.6–1.5). This association was independent of HPV type in the SCC tumor tissue. There was an association between specific serotypes of C. trachomatis and SCC for 6 of the 10 serotypes: B (OR 3.6, 95% CI 1.5–8.4), D (OR 2.1, 95% CI, 1.2–3.5), E (OR 2.4, 95% CI, 1.4–3.9), G (OR 3.0, 95% CI, 1.1–7.9), I (OR 4.2, 95% CI, 1.5–11.7), and J (OR 2.3, 95% CI, 1.0–5.1), but not for the 4 types (C, F, H, and K) that were present at very low prevalence in this population. There was an increased risk of SCC, but not AC, associated with antibodies to C. trachomatis that was not serotype specific. © 2006 Wiley‐Liss, Inc.
Inflammation and IGF‐I activate the Akt pathway in breast cancer
Authors: Prueitt Robyn L. , Boersma Brenda J. , Howe Tiffany M. , Goodman Julie E. , Thomas Douglas D. , Ying Lei , Pfiester Candice M. , Yfantis Harris G. , Cottrell John R. , Lee Dong H. , Remaley Alan T. , Hofseth Lorne J. , Wink David A. , Ambs Stefan
Published: November 2006

Akt signaling may promote breast cancer progression and poor disease outcome. We hypothesized that serum insulin‐like growth factor I (IGF‐I) and a proinflammatory tumor environment induce phosphorylation of Akt and downstream targets of Akt in breast cancer. We studied the relationship between Akt pathway activation, IGF‐I and markers of inflammation, e.g., nitric oxide synthase‐2 (NOS2), cyclooxygenase‐2 (COX2) and tumor phagocyte density, in 248 breast tumors. We also examined the association of Akt phosphorylation with breast cancer survival. We observed that phosphorylation of Akt, BAD and caspase‐9 correlated strongly with the expression of the 2 proinflammatory enzymes, NOS2 and COX2, in breast tumors (p < 0.001; Spearman rank correlation). Both NOS2 and COX2 expression were independently associated with Akt phosphorylation in the multivariate analysis. Serum IGF‐I concentrations and the IGF‐I/IGFBP3 ratio correlated with Akt phosphorylation at Thr308 and Ser473 in breast tumors (p ≤ 0.05; Spearman rank correlation). The association with Akt phosphorylation at Thr308 remained statistically significant in the multivariate analysis. Akt pathway activation was not associated with overall survival in the unstratified analysis, but we observed a statistical interaction between Akt phosphorylation and tumor phagocyte density on breast cancer survival (pinteraction < 0.05). We further corroborated our findings in cell culture models by demonstrating that ANA‐1 macrophages, nitric oxide and prostaglandin E2 induce Akt phosphorylation in human breast cancer cells. In summary, a proinflammatory environment was found to activate the Akt pathway in breast cancer, and may modify the association between the Akt phosphorylation status and breast cancer survival. © 2006 Wiley‐Liss, Inc.
Aberrant promoter methylation of insulin‐like growth factor binding protein‐3 gene in human cancers
Authors: Tomii Kunitoshi , Tsukuda Kazunori , Toyooka Shinichi , Dote Hideaki , Hanafusa Tadashi , Asano Hiroaki , Naitou Minoru , Doihara Hiroyoshi , Kisimoto Takumi , Katayama Hideki , Pass Harvery I. , Date Hiroshi , Shimizu Nobuyoshi
Published: November 2006

Insulin‐like growth factor binding protein‐3 (IGFBP‐3) is postulated to be a mediator of growth suppression signals. Here, we examined the methylation status of IGFBP‐3 to correlate to clinicopathological factors in human cancers. The methylation status of IGFBP‐3 was determined by bisulfite DNA sequencing and was correlated with expression semi‐quantified by real‐time RT‐PCR to develop a methylation‐specific PCR (MSP) assay for IGFBP‐3. Using the MSP assay, we examined the methylation status of IGFBP‐3 in gastric cancer (GC), colorectal cancer (CRC), breast cancer (BC) and malignant mesothelioma (MM). IGFBP‐3 methylation was detected in 6 of 13 (46%) and 16 of 24 (67%) GC cell lines and tumors, respectively; 4 of 8 (50%) and 15 of 26 (58%) CRC cell lines and tumors, respectively; 3 of 11 (27%) and 7 of 39 (18%) BC cell lines and tumors, respectively and 1 of 5 (20%) and 18 of 56 (32%) MM cell lines and tumors, respectively. Interestingly, the methylation status of MM specimens from Japanese patients (75%, 12 out of 16 patients) was significantly higher than those from the USA (15%, 6 out of 40 patients) (p < 0.0001), suggesting the presence of ethnic differences in the IGFBP‐3 methylation status. We also found that IGFBP‐3 methylation was preferentially present in GCs arising in the lower‐third of the stomach (p = 0.079). In summary, our results showed that IGFBP‐3 methylation played an important role in the silencing of its expression, suggesting that IGFBP‐3 may act as a tumor suppressor gene in several human cancers examined. © 2006 Wiley‐Liss, Inc.
Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes
Authors: Weber Jean‐Christophe , Meyer Nicolas , Pencreach Erwan , Schneider Anne , Guérin Eric , Neuville Agnès , Stemmer Christine , Brigand Cécile , Bachellier Philippe , Rohr Serge , Kedinger Michèle , Meyer Christian , Guenot Dominique , Oudet Pierre , Jaeck Daniel , Gaub Marie‐Pierre
Published: November 2006

In colorectal cancer, the molecular alterations that lead to metastasis are not clearly established, probably because of their high genetic complexity. To identify combinations of genetic changes involved in tumor progression and metastasis, we focused on chromosome instable (CIN) colon cancers. We compared by allelotyping of 33 microsatellites, the genomic alterations of 38 primary colon tumors with the synchronously resected matched liver metastases (CLM). We observed that (i) the number of patients with alterations at certain loci did not differ significantly between the whole primary tumor and the paired CLM, (ii) a group of patients had fewer alterations in the metastasis when compared with the matched primary tumor. A 2‐way hierarchical unsupervised clustering of the allelotyping data revealed 2 tumor subtypes that have different levels of CIN (CIN‐High, CIN‐Low). Both subtypes have a minimal common set of alterations at chromosomes 8p, 17p and 18q, but does not include alteration at 5q or mutation at K‐Ras. These 2 subtypes were also observed using a collection of 104 independent primary CIN colon tumors. In addition, we found a third subtype, consisting of tumors with a very low number of alterations not associated with specific loci (CIN‐Very Low). We found that colon carcinogenesis may require a minimal set of alterations and that, in contrast to the current hypothesis, the level of CIN does not correlate with tumor progression. Therefore, our results suggest that metastasis potential could be present at very early stages of tumor development. © 2006 Wiley‐Liss, Inc.
Expression and differential signaling of heregulins in pancreatic cancer cells
Authors: Kolb Armin , Kleeff Jörg , Arnold Nichole , Giese Nathalia A. , Giese Thomas , Korc Murray , Friess Helmut
Published: November 2006

The EGF family of ligands and receptors plays an important role in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) and contributes to its aggressiveness. A number of molecular approaches have been developed to block these pathways, and studies have already proven the clinical benefit of this concept in PDAC. In the present study, we sought to determine the potential role of heregulins (HRGs), a family of EGF‐like growth factors, in PDAC. Quantitative RT‐PCR analysis revealed that HRGs as well as its signaling ErbB receptors were present in 4 of 4 human pancreatic cancer cell lines (PCCL). HRG‐β1 stimulated the growth of 3 of 4 PCCL, whereas HRG‐α1 inhibited cell growth in 3 of 4 cell lines. Responses towards HRGs could in part be predicted by ErbB2 and ErbB3 expression levels. HRGs induced phosphorylation of different ErbB receptors as well as activation of MAPK, p38MAPK, JNK and PI3K in a cell‐ and ligand‐specific manner. In vivo, HRG was upregulated in pancreatic cancer tissues and localized predominantly in the cancer cells. High HRG‐β levels but not HRG‐α levels were associated with decreased patient survival. In conclusion, HRG is expressed by pancreatic cancer cells and influences pancreatic cancer cell growth and patient survival. © 2006 Wiley‐Liss, Inc.
In between worlds: G.N. Lewis, the shared pair bond and its multifarious contexts
Authors: Simões Ana
Published: November 2006

In this paper, I will look at the rather convoluted discovery process which gave birth to the concept of the shared electron pair bond as developed by G.N. Lewis, to be subsequently appropriated by the American founders of quantum chemistry, and highlight the complex relations between conceptual development and the different contexts in which ideas are created and presented. I will show how the successive installments of Lewis's model of the chemical bond were supported by and gained credence from an epistemological background in which Lewis explored the relations of chemistry to physics. Furthermore, they were shaped by the changing public contexts in which the successive metamorphoses of the ideas took place and their epistemological background was outlined and explored. The complexities which are always associated with a discovery process can therefore be illuminated if one pays attention to different interactive realms—the conceptual, epistemological, and the presentational one. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2007
Lipid‐protein cargo transfer: A mode of direct cell‐to‐cell communication for lipids and their associated proteins
Authors: Laffafian Iraj , Hallett Maurice B.
Published: November 2006

Cells in tissues or in experimental cell colonies respond to stimuli in a co‐ordinated manner when they are electrically and chemically coupled by gap junctions. These junctions permit the cell‐to‐cell passage of small molecules, such as inositol tris phosphate (IP3) within the colony and are important in co‐ordinating tissue activity. This is the only recognised mechanism of direct chemical signalling that does not involve the release of an extracellular messenger between cells. However, the data in this article demonstrates a new mode of intercellular communication. Two potentially important signalling lipids, PIP2 and ganglioside G‐M1 were shown to move between cells in colonies by tracking (i) fluorescent lipids loaded into the plasma membranes of individual cells in a cell colony using a novel micropipette technique and (ii) movement of fluorescent lipids after localised photobleaching. Furthermore, a large protein molecule, cholera toxin B subunit bound to extracellularly facing ganglioside G‐M1 was also shown to transfer between cells. The transfer was inhibited by pre‐treatment with poly‐L‐lysine and polyethylenimine, suggesting a role for tight junctions, perhaps by permitting diffusion of lipids and their protein “cargo” across these cell‐to‐cell contact points. This is a hitherto unsuspected form of molecular signalling within cell colonies and tissues which may have implications for understanding co‐ordinated cell colony behaviour. J. Cell. Physiol. 210: 336–342, 2007. © 2006 Wiley‐Liss, Inc.
Chondrocyte hypertrophy and apoptosis induced by GROα require three‐dimensional interaction with the extracellular matrix and a co‐receptor role of chondroitin sulfate and are associated with the mitochondrial splicing variant of cathepsin B
Authors: Olivotto Eleonora , Vitellozzi Roberta , Fernandez Patricia , Falcieri Elisabetta , Battistelli Michela , Burattini Sabrina , Facchini Annalisa , Flamigni Flavio , Santi Spartaco , Facchini Andrea , Borzi' Rosa Maria
Published: November 2006

CXCR2 ligands contribute to chondrocyte hypertrophy and apoptosis, important determinants in cartilage pathophysiology. We unraveled the kinetics of signaling, biochemical, transcriptional, and morphological events triggered by GROα in human osteoarthritic chondrocytes kept in three‐dimensional culture. p38 MAPK activation was assessed with a highly sensitive ELISA. Effector caspase activation was evaluated by cleavage of a fluorogenic substrate. Gene expression of key markers of hypertrophy (MMP‐13, Runx‐2) and matrix synthesis (aggrecan), and of cathepsin B isoform CB(‐2,3) was evaluated by real time PCR. Occurrence of the morphological markers of apoptosis was investigated by transmission electron microscopy (TEM). GROα led to p38 MAPK activation in passaged chondrocytes cultured in micromass but not as a high‐density monolayer. This caused the downstream triggering of chondrocyte hypertrophy (MMP‐13 and Runx‐2 upregulation, and calcium deposition) and apoptosis/anoikis following concurrence of matrix degrading activity, and inhibition of matrix synthesis which also involved the induction of CB(‐2,3). These phenomena proved to be dependent on the co‐receptor role of sulfated glycosaminoglycans (sGAG) and the activation of p38 MAPK, since they were abrogated either by preincubation with soluble chondroitin‐4 sulfate or p38 MAPK inhibitors. The co‐receptor role of sGAG was further demonstrated by colocalization experiments of these molecules with GROα in the stimulated micromasses. These findings suggest that extracellular matrix exerts a regulatory role in chondrocytes differentiation, and that meaningful investigation of the effects of chemokines on chondrocyte biology requires culture conditions respectful of both the differentiated status of the chondrocytes and of their three‐dimensional interaction with the extracellular matrix. J. Cell. Physiol. 210: 417–427, 2007. © 2006 Wiley‐Liss, Inc.
Assessment of lung development using hyperpolarized helium‐3 diffusion MR imaging
Authors: Altes Talissa A. , Mata Jaime , de Lange Eduard E. , Brookeman James R. , Mugler John P.
Published: November 2006

Purpose

To determine whether hyperpolarized helium‐3 (HHe) diffusion MR can detect the expected enlargement of alveoli that occurs with lung growth during childhood.

Materials and Methods

A total of 29 normal subjects aged four to 30 years underwent HHe diffusion MR imaging with theb‐value pair 0, 1.6 second/cm2. A second acquisition during a separate breathhold was performed using theb‐value pair 0, 4 second/cm2to evaluate the dependence onb‐value. The mean apparent diffusion coefficient (ADC) and lung volume for each acquisition and each subject was determined.

Results

Subjects as young as four years of age were able to cooperate with the imaging procedure. The mean ADC increased with increasing subject age (r = 0.8;P< 0.001), with a 55% increase in mean ADC from the youngest to oldest subject. Lung volumes measured on MR were highly repeatable for the two HHe MR acquisitions (r = 0.980,P< 0.001). The mean ADC values measured with the two differentb‐value pairs were highly correlated (r = 0.975;P< 0.001), but the higherb‐value pair resulted in slightly lower mean ADCs (P< 0.001).

Conclusion

HHe diffusion MR appears to detect the expected increase in alveolar size during childhood, and thus HHe MR may be a noninvasive method to assess development of the lung microstructure. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Fat suppression with spectrally selective inversion vs. high spectral and spatial resolution MRI of breast lesions: Qualitative and quantitative comparisons
Authors: Fan Xiaobing , Abe Hiroyuki , Medved Milica , Foxley Sean , Arkani Sanaz , Zamora Marta A. , Olopade Olufunmilayo I. , Newstead Gillian M. , Karczmar Gregory S.
Published: November 2006

Purpose

To compare conventional fat‐suppressed MR images of the breast to images derived from high spectral and spatial resolution MR data. Image quality and the level of fat suppression are compared qualitatively and quantitatively.

Materials and Methods

Women with suspicious breast lesions found on X‐ray mammography were imaged on 1.5 Tesla GE SIGNA scanners. High spectral and spatial resolution (HiSS) data were acquired using echo‐planar spectroscopic imaging. Images with intensity proportional to the water signal peak height in each voxel were synthesized. Conventional fat‐suppressed images were acquired using a frequency selective inversion method. The experimental (HiSS) and conventional images were compared by experienced radiologists to evaluate the quality of fat suppression. In addition, fat suppression and image quality were evaluated quantitatively.

Results

Fat suppression, tumor edge delineation, lesion conspicuity, and image texture were improved in the peak height images derived from HiSS data.

Conclusion

The results demonstrate that the water peak height images obtained from HiSS data potentially could improve the quality of fat suppression, detection and diagnosis of breast cancer. HiSS allowed detection of lesions and evaluation of lesion morphology prior to contrast media injection. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Open‐chest 31P magnetic resonance spectroscopy of mouse heart at 4.7 Tesla
Authors: Lee Joseph , Hu Qingsong , Nakamura Yasuhiro , Wang Xiaohong , Zhang Xiaoliang , Zhu Xiaohong , Chen Wei , Yang Qinglin , Zhang Jianyi
Published: November 2006

Purpose

To develop a rapid, robust, and accurate method for assessing myocardial energetics in mice and demonstrate its applicability to mouse models of acquired and genetic heart disease.

Materials and Methods

We combined surface coil localization (10‐mm diameter, tunable between 1H and 31P, using adiabatic half‐passage radiofrequency pulses) and surgery (electrocautery removal of anterior chest wall) to create an open‐chest method for acquiring in vivo 31P nuclear magnetic resonance (NMR) cardiac spectra from mice at 4.7T within 12 minutes. Normal BALB/c mice, BALB/c with myocardial infarction (MI), cardiomyocyte‐restricted peroxisome proliferator‐activated receptor‐delta knockout (KO) (CR‐PPARd–/–) and control loxP‐flanked Ppard (Ppardflox/flox) mice were examined.

Results

The mean phosphocreatine (PCr)/adenosine triphosphate (ATP) ratios in control BALB/c mice, BALB/c MI mice, Ppardflox/flox mice, and PPAR‐δ KO mice were 2.13 ± 0.09 (N = 11), 1.35 ± 0.07 (N = 9, P < 0.001 vs. BALB/c control), 1.92 ± 0.09 (N = 5), and 1.31 ± 0.12 (N = 5, P < 0.005 vs. Ppardflox/flox control), respectively. The significant depression of myocardial PCr/ATP we observed in these genetic/acquired models of heart disease was in accord with previous data from analogous large animal models. No NMR signal contamination from chamber blood or adjacent skeletal muscle was identified.

Conclusion

This new technique provides cardiac 31P spectra suitable for accurate quantitative analysis in a relatively short acquisition time, is suitable for terminal studies of mouse myocardial energy metabolism, and could be installed in virtually any NMR laboratory to study myocardial energetics in numerous mouse models of human heart disease. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Estimation of pulse wave velocity in main pulmonary artery with phase contrast MRI: Preliminary investigation
Authors: Peng Hsu‐Hsia , Chung Hsiao‐Wen , Yu Hsi‐Yu , Tseng Wen‐Yih I.
Published: November 2006

Purpose

To assess the feasibility and reproducibility of a noninvasive MRI method to measure pulse wave velocity (PWV) in the main pulmonary artery (MPA).

Materials and Methods

A total of 17 subjects without history of pulmonary diseases (38.2 ± 18.4 years) participated in this study. Series of MR velocity maps of the MPA were acquired at 2 cm above the pulmonary valves using a two‐dimensional phase‐contrast sequence. Effective temporal resolution was 11 msec after interleaving two dynamic series with different values of electrocardiograph (ECG) trigger delay. PWV was derived as the rate of MPA flow variations per unit change in MPA cross‐sectional area, during early systole. Seven healthy subjects underwent three repetitive examinations to investigate intrascan and interscan reproducibility.

Results

Flow vs. area was highly linear in the MPA during early systole, with Pearson's coefficients ranging from 0.982 to 0.999, rendering derivation of PWV with little difficulty. Average value of PWV in MPA was 1.96 ± 0.27 m/second, in good agreement with literature values measured using invasive means. The percentage intra‐ and interscan differences were 5.46% and −10.86%, respectively.

Conclusion

Phase‐contrast MRI to noninvasively measure PWV in the MPA is feasible with good reproducibility. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Evaluation of carotid artery wall volume measurement using novel semiautomated analysis software
Authors: Varghese Anitha , Merrifield Robert D. , Crowe Lindsey A. , Collins Steven A. , Keenan Niall G.J. , Firmin David N. , Yang Guang Zhong , Pennell Dudley J.
Published: November 2006

Purpose

To evaluate semiautomated analysis software for measuring the total carotid arterial wall volume (TWV) as a measure of atheroma burden.

Materials and Methods

Semiautomated‐software and manual analyses of TWV measured by cardiovascular magnetic resonance (CMR) were compared in two phantom models, 10 subjects with no known carotid artery disease, and eight subjects with known carotid disease. The subjects were scanned twice for reproducibility.

Results

In subjects with no known carotid disease, semiautomated analysis of 98% of slices showed an improved interstudy coefficient of variation (COV) compared to manual analysis of 50% of slices (4.0% vs. 6.2%, P = 0.02). The proportion of matched cross‐sectional slices usable for TWV measurement was superior (99% vs. 49%, P = 0.005) and the median analysis time was shorter (31 minutes vs. 90 minutes, P < 0.001) using the semiautomated software. In subjects with known carotid disease, semiautomated (99% of slices) and manual (56% of slices) analyses had comparable interstudy COVs (4.1% vs. 3.9%, P = 0.01). However, the proportion of matched cross‐sectional slices usable for TWV measurement was greater using semiautomated contouring (96% vs. 56%, P = 0.01).

Conclusion

Carotid CMR measurement of TWV using novel semiautomated analysis software shows good reproducibility, enables greater coverage of arterial vessel wall length, and is considerably faster compared to manual contouring. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
In Situ AP/MALDI‐MS characterization of anchored matrix metalloproteinases
Authors: Grasso Giuseppe , Fragai Marco , Rizzarelli Enrico , Spoto Giuseppe , Yeo Kwon Joo
Published: November 2006

Several different procedures are available for the immobilization of proteins on solid supports, as many advantages derive from this approach, such as the possibility to develop new protein solid‐state assays. Enzymes that are anchored on gold surfaces can interact with several different molecules in a tag‐free environment, opening the way to surface plasmon resonance (SPR) investigations. Nevertheless, it is often important to know the identity of the affinity‐retained analyte, and mass spectrometric analysis, via its unique molecular mass identification, represents a very valuable complementary method.

There are many pieces of evidence to suggest that matrix metalloproteinases (MMPs) are involved in normal and pathological processes, including embryogenesis, wound healing, inflammation, arthritis and cancer, but presumably also exhibiting other functions. The search for new inhibitors of MMPs has prompted research towards the development of new solid‐state assays for the rapid evaluation of MMP activity. We have already reported the possibility of measuring the activity of MMP‐1 anchored on solid support by coupling SPR with ESI‐MS analysis. In this work, we show the in situ atmospheric pressure (AP) MALDI‐MS characterization of MMPs anchored on a gold chip with known surface coverage. The study extends the MS analysis to different proteins, and sequence coverage is reported for different digestion and MS procedures. Copyright © 2006 John Wiley & Sons, Ltd.