bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of ethylphosphate on azobenzene‐containing thermotropic liquid‐crystalline polymers
Authors: Kumaresan S. , Kannan P.
Published: November 2003

A new series of liquid‐crystalline polymers with azobenzene mesogens and an even number of methylene spacers along with phosphorus heterogeneity were synthesized. The structures of the monomers and polymers were characterized with various spectral techniques. The thermal analyses were performed with thermogravimetric analysis and differential scanning calorimetry (DSC). The formation of the liquid‐crystalline phase was confirmed with hot‐stage optical polarizing microscopy. All the polymers exhibited grainy and nematic textures during melting; this was confirmed by DSC analysis. The char yield of the polymers was quite high and was related to the formation of phosphoric acid. The glass‐transition temperature, melting temperature, and isotropization temperature were quite low. The reduction in the transition temperature could be attributed to the incorporation of the phosphorus heterogeneity and pendant ethyl group. Molecular modeling studies supported the experimental data obtained. The suitability of these polymers for optical data storage was studied with ultraviolet spectroscopy. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 455–462, 2004
Resonance Raman scattering of cytochrome P450 BM3 and effect of imidazole inhibitors
Authors: Smith S. J. , Munro A. W. , Smith W. E.
Published: November 2003

Resonance Raman scattering from cytochrome P450 BM3 is obtained with a Raman microprobe using 406‐nm excitation with an accumulation time of a few seconds. The small sample size and rapid measurement time make the routine characterization of P450 systems by resonance Raman spectroscopy easier. Addition of imidazole and imidazole derivatives as inhibitors causes the appearance of additional peaks due to vinyl modes, increases the relative intensity of symmetric modes that would be A1g in D4h symmetry, and causes a large drop in the intensity of ν11. This information indicates that the ligation of imidazoles to the heme iron causes the alignment of the vinyl modes with the plane of the heme ring and reduces the out of plane distortion of the ring. The effect of both inhibitors is similar but there is a subtle difference in the extent of the reduction in the intensity of ν11, which suggests that steric effects within the pocket are having some effect. © 2003 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 70: 620–627, 2003
Conformational analysis of melittin in solution phase: Vibrational circular dichroism study
Authors: Wang Feng , Polavarapu Prasad L.
Published: November 2003

The vibrational absorption and vibrational circular dichroism (VCD) spectra of melittin in D2O solutions at different pH values, different salt concentrations, or different 2,2,2‐trifluoroethanol (TFE) concentrations are recorded in the amide I′ (1850–1600 cm−1) region. Two models are used to simulate this peptide in different conditions, and a coupled oscillator program is used to obtain the calculated absorption and VCD spectra. This study indicates that melittin adopts a mixed structure in D2O solution at low pH, low salt concentration, or low TFE concentration. With an increase in pH, salt concentration, or TFE concentration, the structure changes to α‐helix and further increases lead to aggregation. These results demonstrate the versatility of VCD in probing the conformations of peptides under different environmental perturbations. © 2003 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 70: 614–619, 2003
Conformational and biological characterization of human parathyroid hormone hPTH(1–34) analogues containing β‐amino acid residues in positions 17–19
Authors: Schievano E. , Mammi S. , Carretta E. , Fiori N. , Corich M. , Bisello A. , Rosenblatt M. , Chorev M. , Peggion E.
Published: November 2003

The N‐terminal 1–34 fragment of parathyroid hormone (PTH) elicits the full spectrum of bone‐related biological activities of the intact native sequences. It has been suggested that the structural elements essential for bioactivity are two helical segments located at the N‐terminal and C‐terminal sequences, connected by hinges or flexible points around positions 12 and 19. In order to assess the relevance of the local conformation around Gly18 upon biological function, we synthesized and characterized the following human (h) PTH(1–34) analogues containing β‐amino acid residues:

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Biological activity and binding affinity of analogue I are one order of magnitude lower than those of the parent compound. In analogue II, both binding affinity and biological activity are partially recovered. Analogues III and V have no binding affinity and very low biological activity. Both bioactivity and binding affinity are partially recovered in analogue IV. The conformational properties of the analogues in aqueous solution containing dodecylphosphocholine micelles were studied by CD, 2D‐nuclear magnetic resonance and molecular dynamics calculations. The results confirmed the presence in all analogues of two helical segments located at the N‐terminal and C‐terminal sequences. The insertion of β‐amino acid residues around position 18 does not cause appreciable conformational differences in the five analogues. The differences in biological activity and binding affinity among the five analogues cannot be related to structural differences in the membrane mimetic environment reported in this study. Our results stress the importance of the side‐chain functionalities in the sequence 17–19 for biological function. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 534–547, 2003
Use of residual dipolar couplings as restraints in ab initio protein structure prediction
Authors: Haliloglu Turkan , Kolinski Andrzej , Skolnick Jeffrey
Published: November 2003

NMR residual dipolar couplings (RDCs), in the form of the projection angles between the respective internuclear bond vectors, are used as structural restraints in the ab initio structure prediction of a test set of six proteins. The restraints are applied using a recently developed SICHO (SIde‐CHain‐Only) lattice protein model that employs a replica exchange Monte Carlo (MC) algorithm to search conformational space. Using a small number of RDC restraints, the quality of the predicted structures is improved as reflected by lower RMSD/dRMSD (root mean square deviation/distance root mean square deviation) values from the corresponding native structures and by the higher correlation of the most cooperative mode of motion of each predicted structure with that of the native structure. The latter, in particular, has possible implications for the structure‐based functional analysis of predicted structures. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 548–562, 2003
Brownian dynamics simulations of glycolytic enzyme subsets with F‐actin
Authors: Lowe S. L. , Adrian C. , Ouporov I. V. , Waingeh V. F. , Thomasson K. A.
Published: November 2003

Previous Brownian dynamics (BD) simulations identified specific basic residues on fructose‐1,6‐bisphophate aldolase (aldolase) (I. V. Ouporov et al., Biophysical Journal, 1999, Vol. 76, pp. 17–27) and glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) (I. V. Ouporov et al., Journal of Molecular Recognition, 2001, Vol. 14, pp. 29–41) involved in binding F‐actin, and suggested that the quaternary structure of the enzymes may be important. Herein, BD simulations of F‐actin binding by enzyme dimers or peptides matching particular sequences of the enzyme and the intact enzyme triose phosphate isomerase (TIM) are compared. BD confirms the experimental observation that TIM has little affinity for F‐actin. For aldolase, the critical residues identified by BD are found in surface grooves, formed by subunits A/D and B/C, where they face like residues of the neighboring subunit enhancing their electrostatic potentials. BD simulations between F‐actin and aldolase A/D dimers give results similar to the native tetramer. Aldolase A/B dimers form complexes involving residues that are buried in the native structure and are energetically weaker; these results support the importance of quaternary structure for aldolase. GAPDH, however, placed the critical residues on the corners of the tetramer so there is no enhancement of the electrostatic potential between the subunits. Simulations using GAPDH dimers composed of either S/H or G/H subunits show reduced binding energetics compared to the tetramer, but for both dimers, the sets of residues involved in binding are similar to those found for the native tetramer. BD simulations using either aldolase or GAPDH peptides that bind F‐actin experimentally show complex formation. The GAPDH peptide bound to the same F‐actin domain as did the intact tetramer; however, unlike the tetramer, the aldolase peptide lacked specificity for binding a single F‐actin domain. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 456–470, 2003
Application of statistical potentials to protein structure refinement from low resolution ab initio models
Authors: Lu Hui , Skolnick Jeffrey
Published: November 2003

Recently ab initio protein structure prediction methods have advanced sufficiently so that they often assemble the correct low resolution structure of the protein. To enhance the speed of conformational search, many ab initio prediction programs adopt a reduced protein representation. However, for drug design purposes, better quality structures are probably needed. To achieve this refinement, it is natural to use a more detailed heavy atom representation. Here, as opposed to costly implicit or explicit solvent molecular dynamics simulations, knowledge‐based heavy atom pair potentials were employed. By way of illustration, we tried to improve the quality of the predicted structures obtained from the ab initio prediction program TOUCHSTONE by three methods: local constraint refinement, reduced predicted tertiary contact refinement, and statistical pair potential guided molecular dynamics. Sixty‐seven predicted structures from 30 small proteins (less than 150 residues in length) representing different structural classes (α, β, α˜/β) were examined. In 33 cases, the root mean square deviation (RMSD) from native structures improved by more than 0.3 Å; in 19 cases, the improvement was more than 0.5 Å, and sometimes as large as 1 Å. In only seven (four) cases did the refinement procedure increase the RMSD by more than 0.3 (0.5) Å. For the remaining structures, the refinement procedures changed the structures by less than 0.3 Å. While modest, the performance of the current refinement methods is better than the published refinement results obtained using standard molecular dynamics. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 575–584, 2003
Prognostic significance of metastatic lymph node size in patients with gastric cancer
Authors: Dhar D K , Kubota H , Kinukawa N , Maruyama R , Kyriazanos I D , Ohno S , Nagasue N
Published: November 2003

Background

Patients with gastric cancer that has metastasized to the lymph nodes are a heterogeneous population with a variable prognosis. Stratification of these patients into prognostic groups is necessary for optimal adjuvant therapy.

Methods

The study comprised 715 patients who had undergone curative resection of a gastric neoplasm. Lymph nodes were sectioned, stained with haematoxylin and eosin, and the diameter of the largest metastatic lymph node (MLN) was measured. Patients with metastatic nodes were divided into groups n1 and n2 according to the size of the MLN. The cut-off level was set at 7 mm by a two-sample log rank test; patients in group n1 had a MLN size of 7 mm or less and those in group n2 had a MLN of 8 mm or more.

Results

Patients were stratified into significant prognostic groups by both the Union International Contra la Cancrum (UICC) node (N) stage and MLN size (n group). The UICC N-stage subcategories were further divided into prognostic groups according to MLN size (n group). On multivariate analysis the MLN size remained independently significant in terms of overall and disease-free survival rates, and the UICC N stage was not significant, independently of the n group. Node-positive patients with fewer than 15 lymph nodes removed at operation could also be stratified into prognostic groups by the n group. Stratification according to the TNM stage and by MLN size was superior to existing UICC TNM staging.

Conclusion

This new method may help clinicians to design a more appropriate treatment strategy for patients with gastric cancer.
Arterial problems in athletes
Authors: Mosley J G
Published: November 2003

Background

Athletes may present with arterial problems that are unusual in the typical patient with peripheral vascular disease. They are often handicapped only at the extremes of physical exertion and may have normal arterial pulses beyond any arterial occlusion.

Methods

A Medline search was undertaken for articles on arterial disease in athletes. Further papers were identified by cross-referencing from the reference lists.

Results

A variety of syndromes has been described that result from unusual trauma to arteries, causing occlusion or rupture. Frequently the blood flow and pressures distal to the arterial disease are normal at rest, and diagnosis is often confused with venous, musculoskeletal or nerve disease. A variety of operative interventions has been described.

Conclusion

Athletes may experience arterial problems that may jeopardize their careers. If recognized promptly, operative intervention may permit a return to the highest level of sporting achievement.
Correlation of electrophysiological and morphological characteristics of enteric neurons in the mouse colon
Authors: Nurgali Kulmira , Stebbing Martin J. , Furness John B.
Published: November 2003

We report on the first correlative study of the electrophysiological properties, shapes, and projections of enteric neurons in the mouse. Neurons in the myenteric plexus of the mouse colon were impaled with microelectrodes containing biocytin, their passive and active electrophysiological properties determined, and their responses to activation of synaptic inputs investigated. Biocytin, injected into the neurons from which recordings were made, was converted to an optically dense product and used to determine the shapes of neurons. By electrophysiological properties, almost all neurons belonged to one of two classes, AH neurons or S neurons. AH neurons had a biphasic repolarization of the action potential, and slow afterhyperpolarizing potentials usually followed the action potentials. S neurons had monophasic repolarizations, no slow afterhyperpolarization, and fast excitatory postsynaptic potentials in response to fibre tract stimulation. By shape, neurons were divided into Dogiel type II (28/136 neurons) and uniaxonal neurons. Dogiel type II neurons had large, smooth‐surfaced cell bodies and several long processes that supplied branches within myenteric ganglia. All Dogiel type II neurons had AH electrophysiology; conversely, most AH neurons had Dogiel type II morphology. The majority of uniaxonal neurons had lamellar dendrites, i.e., Dogiel type I morphology. They projected to the circular muscle (circular muscle motor neurons), to the longitudinal muscle (longitudinal muscle motor neurons), and to other myenteric ganglia (interneurons) and in some cases could not be traced to target cells. All S neurons were uniaxonal. A small proportion of uniaxonal neurons (3/70) had AH electrophysiology. Fast excitatory synaptic potentials were only recorded from uniaxonal neurons and were in most cases blocked by nicotinic receptor antagonists. A small component of fast excitatory transmission in some neurons was antagonized by the purine receptor antagonist PPADS. Slow excitatory postsynaptic potentials were observed in both AH and S neurons. Slow inhibitory postsynaptic potentials were recorded from S neurons. We conclude that the major classes of neurons are Dogiel type II neurons with AH electrophysiological properties and Dogiel type I neurons with S electrophysiological properties. The S/Dogiel type I neurons include circular muscle motor neurons, longitudinal muscle motor neurons, and interneurons. J. Comp. Neurol. 468:112–124, 2004. © 2003 Wiley‐Liss, Inc.
Corticothalamic cells in layers 5 and 6 of primary and secondary sensory cortex express GAP‐43 mRNA in the adult rat
Authors: Feig Sherry L.
Published: November 2003

The expression of a presynaptic phosphoprotein, growth‐associated protein (GAP)‐43, is associated with synaptogenesis during development and synaptic remodeling in the adult. This study examined GAP‐43 mRNA expression and distribution in primary and secondary areas of visual, auditory, and somatosensory cortex of the adult rat, by in situ hybridization with a digoxigenin‐coupled mRNA probe, focusing particularly on the corticothalamic cells in layers 5 and 6. In the six cortical areas studied, GAP‐43 mRNA was expressed predominantly in layers 5 and 6 and was greater in secondary than primary areas. There were densely labeled cells in layers 5 and 6 of all areas, which showed a restricted sublaminar distribution in primary areas and more even distribution in secondary areas. Combining retrograde transport of rhodamine beads with in situ hybridization in visual and auditory cortex showed that corticothalamic cells in layers 5 and 6 express GAP‐43 mRNA. There are more of these GAP‐43 mRNA positive corticothalamic cells in layer 5 of secondary areas than in primary areas. The evidence suggests that in the adult rat, plasticity related to GAP‐43 is present in primary and secondary sensory cortex and more so in secondary areas. J. Comp. Neurol. 468:96–111, 2004. © 2003 Wiley‐Liss, Inc.
CHEK2 1100delC is not a risk factor for male breast cancer population
Authors: Syrjäkoski Kirsi , Kuukasjärvi Tuula , Auvinen Anssi , Kallioniemi Olli‐P
Published: November 2003

Genetic risk factors for male breast cancer (MBC) are poorly understood. High penetrance genes such as BRCA1 or BRCA2 account for only a small proportion of the disease. A 1100delC mutation in CHEK2 (previously known as CHK2), a cell‐cycle checkpoint kinase, has been implicated in predisposition of Li‐Fraumeni syndrome (LFS) and breast cancer in families suggestive of LFS. This 1100delC mutation has also been shown to confer a 2‐fold increase of breast cancer risk in women and a 10‐fold increase of risk in men. It was estimated to account for 1% of breast cancers in women and as much as 9% of breast cancers in men at the population level based on analysis of breast cancer families without BRCA1 or BRCA2 mutations. We wanted to evaluate the significance of CHEK2 1100delC in predisposition to MBC by assessing its frequency in a population‐based material of 114 Finnish MBC patients. Two patients (1.8%) carried the 1100delC mutation. The mutation frequency among MBC cases was similar to that seen in population controls (26/1885, 1.4%). Our results indicate that CHEK2 1100delC variant does not substantially increase the risk of male breast cancer at the population level. We cannot exclude the fact that a small fraction of hereditary, family‐positive male breast cancers could be attributable to CHEK2 mutations. © 2003 Wiley‐Liss, Inc.
Human agmatinase is diminished in the clear cell type of renal cell carcinoma
Authors: Dallmann Kerstin , Junker Heike , Balabanov Stefan , Zimmermann Uwe , Giebel Jürgen , Walther Reinhard
Published: November 2003

The proteome of RCC was analyzed by 2D PAGE to search for tumor‐associated proteins. Agmatinase, which hydrolyzes agmatine to putrescine and urea, was identified by mass spectrometry and database searches and shown to be downregulated in tumor cells. Additionally, RT‐PCR and Northern blot analyses demonstrated a clearly decreased amount of agmatinase mRNA in tumor cells. The differential expression of agmatinase mRNA was confirmed at the protein level. Western blot analysis showed almost no detectable agmatinase protein in tumor cells compared to corresponding normal renal tissue. Agmatinase mRNA is most abundant in human liver and kidney but expressed to a lesser extent in several other tissues, including skeletal muscle and small intestine. The human agmatinase gene encodes a 352‐residue protein with a putative mitochondrial targeting sequence at the N‐terminus. Using transfection and immunohistochemical studies, we show that agmatinase is localized in the mitochondria. Immunohistochemical studies revealed that agmatinase in the normal kidney is restricted to tubulus epithelial cells, while in tumors staining was low and heterogeneous. Thus, expression of human agmatinase is altered in RCC. We discuss the consequences of these findings in terms of polyamine, NO metabolism and macrophage function. © 2003 Wiley‐Liss, Inc.
Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women
Authors: Lukanova Annekatrin , Lundin Eva , Micheli Andrea , Arslan Alan , Ferrari Pietro , Rinaldi Sabina , Krogh Vittorio , Lenner Per , Shore Roy E. , Biessy Carine , Muti Paola , Riboli Elio , Koenig Karen L. , Levitz Mortimer , Stattin Pär , Berrino Franco , Hallmans Göran , Kaaks Rudolf , Toniolo Paolo , Zeleniuch‐Jacquotte Anne
Published: November 2003

Experimental and epidemiological data support a role for sex steroid hormones in the pathogenesis of endometrial cancer. The associations of pre‐diagnostic blood concentrations of estradiol, estrone, testosterone, androstenedione, DHEAS and SHBG with endometrial cancer risk were investigated. A case‐control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Cases were 124 postmenopausal women with invasive endometrial cancer. For each case, 2 controls were selected, matching the case on cohort, age and date of recruitment. Only postmenopausal women who did not use exogenous hormones at the time of blood donation were included. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated by conditional logistic regression. ORs (95% CI) for endometrial cancer for quartiles with the highest hormone levels, relative to the lowest were as follows: 4.13 (1.76–9.72), ptrend = 0.0008 for estradiol, 3.67 (1.71–7.88), ptrend = 0.0007 for estrone, 2.15 (1.05–4.40), ptrend = 0.04 for androstenedione, 1.74 (0.88–3.46), ptrend = 0.06 for testosterone, 2.90 (1.42–5.90), ptrend = 0.002 for DHEAS and 0.46 (0.20–1.05), ptrend = 0.01 for SHBG after adjustment for body mass index, use of oral contraceptives and hormone replacement therapy. The results of our multicenter prospective study showed a strong direct association of circulating estrogens, androgens and an inverse association of SHBG levels with endometrial cancer in postmenopausal women. The effect of elevated androstenedione and testosterone levels on disease risk seems to be mediated mainly through their conversion to estrogens, although an independent effect of androgens on tumor growth cannot be ruled out, in particular in the years close to diagnosis. © 2003 Wiley‐Liss, Inc.
Intake of beer inhibits azoxymethane‐induced colonic carcinogenesis in male Fischer 344 rats
Authors: Nozawa Hajime , Yoshida Aruto , Tajima Osamu , Katayama Mikio , Sonobe Hiromi , Wakabayashi Keiji , Kondo Keiji
Published: November 2003

Modulatory effects of beer consumption on azoxymethane (AOM)‐induced rat colonic carcinogenesis in male Fischer 344 rats were investigated. Single cell gel electrophoresis assay indicated that DNA damage of colonocytes, induced by a single AOM injection (15 mg/kg body weight), was significantly reduced in rats fed beer or malt extract for 2 weeks. Examination of aberrant crypt foci (ACF) formation in colonic mucosa, induced by AOM (15 mg/kg body weight; twice weekly), revealed that feeding of beer during the whole experimental period of 5 weeks significantly reduced the number of ACF by 35%. In the post‐initiation protocol, a reduction in ACF formation by 26% was not significant. The efficacy in inhibition of ACF formation varied with the brand of beer. ACF formation was significantly reduced in rats treated with freeze‐dried beer (FD Beer), but not with ethanol, suggesting that nonvolatile components of beer are responsible for the reduction. Significant suppression of ACF formation was observed in groups treated with hot water extract of malt, especially with extracts of colored malts, although no reduction was observed by feeding with hops extract. A long‐term experiment of 42 weeks indicated that intake of beer decreased tumor incidence by 22% and decreased the number of neoplastic lesions, including adenocarcinomas and adenomas, by 44%. These results suggest that components of beer have chemopreventive effects on colonic carcinogenesis induced by AOM and that intake of beer may contribute to a reduction in the risk of cancer susceptibility. © 2003 Wiley‐Liss, Inc.
Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids
Authors: Hoevel Thorsten , Macek Robert , Swisshelm Karen , Kubbies Manfred
Published: November 2003

Members of the claudin family together with occludin are the major constituents of the tight junction (TJ) complex. The human homologue of the murine CLDN1, previously called SEMP1, was identified by differential expression analysis, and the CLDN1 mRNA was found to be downregulated or completely lost in human breast cancer cells in vitro. Retroviral‐induced CLDN1 reexpression in breast cancer cells results in plasma membrane homing of the protein and reconstitution of paracellular flux inhibition, which is not dependent on the presence of occludin protein. In this report, we investigated the physiologic role of CLDN1 in CLDN1‐transduced MDA‐MB 361 breast tumor cells in adherent 2D and suspension 3D spheroid cell cultures. Retroviral‐transduced bulk cultures were FACS‐sorted to enrich for 100% CLDN1‐positive clonal derivatives with similar expression levels of CLDN1 mRNA and protein. There was no difference in proliferation and cell death characteristics in 2D adherent cell cultures of CLDN1‐positive compared to control CLDN1‐negative and mock‐transduced cell cultures. In contrast, the majority of the CLDN1‐transduced derivatives displayed a significant elevation of apoptosis that became evident as early as 2 days after 3D spheroid culture onset. This elevated apoptosis was independent of the volume of established spheroids. The cellular immunofluorescence analysis of CLDN1 protein expression in transduced bulk cultures revealed a CLDN1‐positive subfraction with a heterogeneous pattern of membrane and cytosolic immunostaining. In the clonal MDA‐MB 361 CLDN1‐positive cultures, we found that a more prominent cell membrane localization correlated with a pronounced increase of apoptosis in tumor spheroids. In parallel, inhibition of the paracellular flux rate was observed. These findings support a potential role of the TJ protein CLDN1 in restricting nutrient and growth factor supplies in breast cancer cells, and they indicate that the loss of the cell membrane localization of the TJ protein CLDN1 in carcinomas may be a crucial step during tumor progression. © 2003 Wiley‐Liss, Inc.
High levels of circulating testosterone are not associated with increased prostate cancer risk: A pooled prospective study
Authors: Stattin Pär , Lumme Sonja , Tenkanen Leena , Alfthan Henrik , Jellum Egil , Hallmans Göran , Thoresen Steinar , Hakulinen Timo , Luostarinen Tapio , Lehtinen Matti , Dillner Joakim , Stenman Ulf‐Håkan , Hakama Matti
Published: November 2003

Androgens stimulate prostate cancer in vitro and in vivo. However, evidence from epidemiologic studies of an association between circulating levels of androgens and prostate cancer risk has been inconsistent. We investigated the association of serum levels of testosterone, the principal androgen in circulation, and sex hormone‐binding globulin (SHBG) with risk in a case‐control study nested in cohorts in Finland, Norway and Sweden of 708 men who were diagnosed with prostate cancer after blood collection and among 2,242 men who were not. In conditional logistic regression analyses, modest but significant decreases in risk were seen for increasing levels of total testosterone down to odds ratio for top vs. bottom quintile of 0.80 (95% CI = 0.59–1.06; ptrend = 0.05); for SHBG, the corresponding odds ratio was 0.76 (95% CI = 0.57–1.01; ptrend = 0.07). For free testosterone, calculated from total testosterone and SHBG, a bell‐shaped risk pattern was seen with a decrease in odds ratio for top vs. bottom quintile of 0.82 (95% CI = 0.60–1.14; ptrend = 0.44). No support was found for the hypothesis that high levels of circulating androgens within a physiologic range stimulate development and growth of prostate cancer. © 2003 Wiley‐Liss, Inc.
CD137 and CD137 ligand constitutively coexpressed on human T and B leukemia cells signal proliferation and survival
Authors: Palma Carla , Binaschi Monica , Bigioni Mario , Maggi Carlo Alberto , Goso Cristina
Published: November 2003

CD137, a member of the tumor necrosis factor receptor family, provides expansion and survival signal to T cells. Its ligand, CD137L, in addition to its ability to costimulate T cells, signals back into antigen presenting cells promoting their activation and differentiation. Recently, CD137 has been proposed as a therapeutic target to improve and sustain anticancer immune response. Several activated T leukemia and B lymphoma cell lines expressed CD137 or CD137L, respectively, and soluble CD137L has been found in sera of leukemia patients. However, the functionality and role of these costimulatory molecules in hematologic malignancies are until now unknown. Interestingly, we observed constitutive CD137 and CD137L coexpression on both human T and B leukemia cell lines. The constitutive CD137 expression on unstimulated T or B leukemia cells presents some differences compared to CD137 expressed on PMA/ionomycin‐activated T leukemia cells. Surprisingly, in spite of the low expression level, both tumor CD137 and CD137L molecules signaled in T and B leukemia cells inducing proliferation and prolonging survival. In addition, CD137/CD137L system ligation opposed the anticancer drug cytotoxic effects, reducing the apoptotic DNA fragmentation and stimulating proliferation of doxorubicin‐escaped leukemia cells. Although the role of leukemia CD137/CD137L system in vivo is unknown, these data suggest that these costimulatory molecules might confer an advantage to hematologic tumors promoting survival, sustaining cellular growth and contributing to drug resistance. © 2003 Wiley‐Liss, Inc.
Quantification of cytokeratin 20, carcinoembryonic antigen and guanylyl cyclase C mRNA levels in lymph nodes may not predict treatment failure in colorectal cancer patients
Authors: Bustin Stephen A. , Siddiqi Shahab , Ahmed Shafi , Hands Rebecca , Dorudi Sina
Published: November 2003

Conventional histopathologic staging of primary colorectal cancers does not allow accurate prognostic stratification within a given tumour stage. Therefore, PCR‐based assays are increasingly used to try to predict more accurately the likelihood of disease progression for the individual patient. Real‐time reverse transcription PCR (RT‐PCR) assays were used to detect and quantitate cytokeratin 20 (ck20), carcinoembryonic antigen (CEA) and guanylyl cyclase C (GCC) mRNA in 149 lymph nodes (LN) from 17 patients with benign disease and 302 LN from 42 patients with colorectal cancer who had curative (R0) resections. None of the markers were specific, with ck20, CEA and GCC mRNA detected in 47%, 89% and 13% of 149 LN, respectively, from patients with benign disease. The sensitivity of all 3 markers was very high, with mRNA detected in 93%, 100% and 97% of 30 histologically involved LN, respectively. There was significant overlap in the mRNA levels of all 3 markers between histologically involved and uninvolved LN. There was no association between mRNA levels and distant recurrence (median follow‐up: 3.94 years, range 3.35–5.12). We conclude that the use of molecular techniques to detect occult disease in LN may suffer from the same limitations as conventional methods. Instead, accurate prognostic stratification requires careful assessment of the likely metastatic potential of the primary cancer. © 2003 Wiley‐Liss, Inc.
Nadir B cell counts are significantly correlated with the risk of Kaposi's sarcoma
Authors: Stebbing Justin , Gazzard Brian , Newsom‐Davis Tom , Nelson Mark , Patterson Steve , Gotch Frances , Mandalia Sundhiya , Bower Mark
Published: November 2003

Infection with HIV‐1 is known to impair B cell function. To further elucidate the role of B cells during infection and tumorigenesis, we studied their numbers in cases of AIDS‐related Kaposi's sarcoma (KS) during the HAART era. Patients with AIDS‐related KS were identified from a database of 4,480 HIV‐1 positive individuals and the incidence of KS and rate ratio was stratified according to nadir number of B cells, measured as the CD19 count. In an unadjusted model, we observed that lower B cell counts were associated with a statistically significant increased risk of KS development (p < 0.001). We also observed a trend toward increased counts during KS resolution. When adjusted for nadir CD4 count in a multi‐variable model, higher B cell counts were protective against KS development (p = 0.015). These data highlight a potential role for B cells and therefore the humoral immune system in KS aetiopathogenesis. © 2003 Wiley‐Liss, Inc.
Theoretical study of ribonucleotide reductase mechanism‐based inhibition by 2′‐azido‐2′‐deoxyribonucleoside 5′‐diphosphates
Authors: Pereira Susana , Fernandes Pedro Alexandrino , Ramos Maria João
Published: November 2003

2′‐Azido‐2′‐deoxyribonucleoside 5′‐diphosphates are mechanism‐based inhibitors of Ribonucleotide Reductase. Considerable effort has been made to elucidate their mechanism of inhibition, which is still controversial and not fully understood. Previous studies have detected the formation of a radical intermediate when the inhibitors interact with the enzyme, and several authors have proposed possible structures for this radical. We have conducted a theoretical study of the possible reactions involved, which allowed us to identify the structure of the new radical among the several proposals. A new reactional path is also proposed that is the most kinetically favored to yield this radical and ultimately inactivate the enzyme. The energetic involved in this mechanism, both for radical formation and radical decay, as well as the calculated Hyperfine Coupling Constants for the radical intermediate, are in agreement with the correspondent experimental values. This mechanistic alternative is fully coherent with remaining experimental data. © 2003 Wiley Periodicals, Inc. J Comput Chem 25: 227–237, 2004
Polymer‐solvent complexes and intercalates prepared under various conditions
Authors: Guenet Jean‐Michel
Published: November 2003

The relevancy of temperature‐composition phase diagrams for the study of polymer‐solvent complexes and intercalates is discussed. In particular the use of Tamman's diagrams for determining the stoichiometric composition is evaluated. Examples of the validity of this approach are taken from isotactic or syndiotactic polystyrene compounds. Also, the effect of the path followed for reaching a T, C coordinate is examined. It is shown that cooling hot, homogeneous solutions at composition C or allowing solvent to diffuse in a solid polymer matrix at temperature T yields basically the same thermal behaviour.
Highly conductive oriented PEO‐based polymer electrolytes
Authors: Golodnitsky D. , Livshits E. , Peled E.
Published: November 2003

This contribution presents an overview of the study of the effect of stretching on semicrystalline and amorphous complexes of poly(ethylene oxide) (PEO) with different salts, such as lithium iodide, lithium trifluoromethane‐sulfonate, lithium hexafluoroarsenate, lithium bis(oxalato)borate and lithium trifluoromethanesulfonimide. In spite of the conventional belief that ion transport in polymer electrolytes (PE) is mediated primarily by polymer segmental motion, we suggest that ion transport occurs preferentially along the PEO helical axis, at least in the crystalline phase. It was found that the more amorphous the PE, the less its lengthwise conductivity is influenced by stretching. It is suggested that the rate‐determining step of ion conduction in semicrystalline LiX:P(EO)20, polymer electrolytes below the melting point (Tm) is “interchain” hopping.
Water‐protein and ligand‐protein interactions as determined by selective NMR relaxation studies
Authors: Rossi Claudio , Martini Silvia , Ricci Maso , Picchi Maria Pia , Bonechi Claudia
Published: November 2003

Water‐macromolecules and ligand‐macromolecules interactions were investigated considering the effects induced by the presence of a macromolecule on both the water and the ligand NMR selective (R1SE) and non‐selective (R1NS) spin‐lattice relaxation rates. The results obtained from the solvent studies were used to describe the solvent dynamics at the macromolecule‐solvent interface. On the other hand, ligand R1SE and (R1NS) analysis allowed the definition of the “affinity index”, [A]LT, an index related to the extent of the macromolecule‐ligand recognition process.
Solid state NMR study of intercalate complexes of poly(ethylene oxide) and small molecules
Authors: Spěváček Jiří , Brus Jiří
Published: November 2003

From solid state NMR spectra, a lower shielding of poly(ethylene oxide) (PEO) protons, in contrast to higher shielding of PEO carbons, has been found for PEO/hydroxybenzene and PEO/LiCF3SO3 complexes in comparison with neat PEO. The same PEO chemical shifts were found both for crystalline and amorphous phase of PEO/LiCF3SO3 polymer electrolyte, confirming the same interaction in both phases. Measurements of 2D 1H CRAMPS exchange NMR spectra have been used to characterize proton distances in complexes of PEO and benzene derivatives. A close contact (∼ 0.3 nm) between aromatic and PEO protons was detected in some cases. From the measurements of the cross polarization 1H → 13C, using Lee‐Goldburg irradiation of 1H nuclei, the distance between LiCF3SO3 carbon and the nearest PEO protons in the PEO/LiCF3SO3 complex was determined.
Crystallization kinetics of poly(ethylene oxide) in mixtures with tetrahydronaphthalene and oligo(dimethyl siloxane‐b‐ethylene oxide) copolymer
Authors: Madbouly Samy A.
Published: November 2003

The crystallization behavior of poly(ethylene oxide) (PEO) in mixtures with oligo(dimethyl siloxane‐b‐ethylene oxide) (COP) and tetrahydronaphthalene (THN) has been investigated. The crystallization kinetics studied isothermally and non‐isothermally using an automated device that monitors the light passing through the systems as functions of time and/or temperature. The crystallization kinetics was found to be strongly influenced by the COP concentration in the mixtures. A substantial decrease in the induction time, t0 (the time needs for the onset of crystallization) and a considerable shift in the crystallization temperature (Tl/s) to higher temperatures have been observed with increasing the concentration of COP in the mixtures during the isothermal and non‐isothermal crystallization processes, respectively. This behavior may be attributed to the difference in the interaction parameters of PEO with THN and COP. The isothermal crystallization kinetics for this system was analyzed on the bases of Avrami approach.
The gel‐like structure of polymer in thin films: an explanation of the thickness dependent glass transition?
Authors: Grohens Yves , Hamon Loic , Spěváček Jiří , Holl Yves
Published: November 2003

The understanding of the origin of the thickness (h) dependent glass transition temperature, Tg(h), reported over the last decade for supported and freely standing thin polymer films, is still unclear. Indeed, the spin‐coating process, the interfacial adsorption as well as the freezing‐in of non‐equilibrated chain conformations and orientations caused by fast solvent evaporation could result in partially disentangled chains which can be depicted as a gel‐like structure. The effect of PMMA stereoregularity on the chain conformation and orientation and its persistence length in thin films is discussed. Moreover, striking evolutions of Tg(h) by changing the nature of the solvent support the assumption of a specific organisation of the chains in thin films which can hold over thickness far above Rg.
Properties of poly(vinyl alcohol)‐graft‐polyacrylamide copolymers depending on the graft length. 3. Benzene solubilization by solutions of the copolymer
Authors: Zagdanskaya Nina , Momot Lesya , Zheltonozhskaya Tatyana , Guenet Jean‐Michel , Syromyatnikov Vladimir
Published: November 2003

The peculiarities of poly(vinyl alcohol)‐graft‐polyacrylamide copolymers (PVA‐g‐PAA), which are characterized by the equal average number (N=9), but various molecular weight (or length) of graft chains, in comparison with individual PAA and PVA, were investigated in aqueous medium. Sharp rise in benzene solubilization in PVA‐g‐PAA solutions at MPAA higher than 4.3·105 has been established. It was shown that such effect is stipulated by the destruction of intramolecular polymer‐polymer complex in the copolymer and increasing the benzene binding to separate PVA‐g‐PAA groups by means of hydrogen bonds. The changes in the PVA‐g‐PAA solubilizing ability as the function of temperature were also investigated. The obtained results are discussed from the point of view of conformational transitions of intramolecular polymer‐polymer complexes (intraPPC), which exist in copolymers, in dependence on the length of graft chains.
Poly(hydroxyethyl methacrylate) membranes: as a hydrogel support for use in immobilized metal affinity chromatography
Authors: Bayramoğlu Gülay , Arıca M. Yakup
Published: November 2003

Lysozyme adsorption onto a dye ligand (Procion Red HE‐3B) immobilized and Cu(II) incorporated poly(2‐hydroxyethylmethacrylate) (pHEMA) membrane, were investigated. The membranes were prepared by UV initiated photopolymerization of HEMA in the presence of an initiator (α‐α′‐azoisobutyronitrile; AIBN). The amount of immobilized dye on the membrane was 112.2 μmol g−1. Lysozyme adsorption on to these membranes from aqueous solutions containing different amounts of lysozyme at different pH was investigated in batch system. Lysozyme adsorption capacity of the dye‐ligand immobilized membrane was 45.6 mg g−1. Lysozyme adsorption capacity of the Cu(II) incorporated membranes (112.3 mg g−1) was greater than that of the Procion Red HE‐3B immobilized membranes. The non‐specific adsorption of lysozyme on the pHEMA membranes was 0.14 mg g−1. More than 97% of the adsorbed lysozyme were desorbed in 60 in the desorption medium containing 1.0 M KSCN at pH 8.0.
1H NMR relaxation study of polymer‐solvent interactions during thermotropic phase transition in aqueous solutions
Authors: Spěváček Jiří , Hanyková Lenka
Published: November 2003

The dynamic‐structural changes and polymer ‐ solvent interactions during the thermotropic phase transition in poly(vinyl methyl ether) (PVME)/D2O solutions in a broad range of polymer concentrations (c = 0.1‐60 wt.‐%) were studied combining the measurements of 1H NMR spectra, spin‐spin (T2) and spin‐lattice (T1) relaxation times. Phase separation in solutions results in a marked line broadening of a major part of polymer segments, evidently due to the formation of compact globular‐like structures. The minority (∼15%) mobile component, which does not participate in the phase separation, consists of low‐molecular‐weight fractions of PVME, as shown by GPC. Measurements of spin‐spin relaxation times T2 of PVME methylene protons have shown that globular structures are more compact in dilute solutions in comparison with semidilute solutions where globules probably contain a certain amount of water. A certain portion of water molecules bound at elevated temperatures to (in) PVME globular structures in semidilute and concentrated solutions was revealed from measurements of spin‐spin and spin‐lattice relaxation times of residual HDO molecules.
1H NMR study of phase transition of uncharged and negatively charged poly(N‐isopropylmethacrylamide) in D2O solutions
Authors: Starovoytova Larisa , Spěváček Jiří , Hanyková Lenka , Ilavský Michal
Published: November 2003

1H NMR spectroscopy has been applied to the analysis of dynamic‐structural changes during temperature‐induced phase transition of non‐ionized poly(N‐isopropylmethacrylamide) (PIPMAm) and ionized copolymers of N‐isopropylmethacrylamide with sodium methacrylate, all in D2O solutions with various polymer concentrations (c = 0.1‐10 wt.‐%) and ionic comonomer mole fractions (i = 0‐10 mole %). It was found that the formation of compact globular‐like structures during the phase transition is independent of polymer concentration for non‐ionized samples; the presence of negative charges on the polymer chains leads to a dependence of the phase transition temperature on c and i. Virtually all PIPMAm segments are in globular‐like structures for low polymer concentrations; for c ⩾ 1 wt.‐%, this holds only for low content i of the ionic comonomer. An increase in c and i leads to a decrease in the fraction of polymer segments in globular‐like structures; for samples with highest values of c and i, the phase transition was not observed.
Polymer‐colloid complexes in three‐component system: poly(styrene‐alt‐maleic acid)‐poly(ethylene oxide)‐silica sol in aqueous medium
Authors: Permyakova Natalya , Zheltonozhskaya Tatyana , Strilchyk Nikolay , Zagdanskaya Nina , Momot Lesya , Syromyatnikov Vladimir
Published: November 2003

Complex formation in the model three‐component system, including polymer‐polymer complex of poly(styrene‐alt‐maleic acid) (PSMA) and poly(ethylene oxide) (PEO), and also silica sol (SiO2) in aqueous solution as a function of molecular weight of PEO and the order of component mixing, were investigated. The degree of binding of PSMA links with PEO and SiO2 as well as the Gibbs energy of formation of the polymer‐polymer complex and polymer‐colloid complexes were defined. It was shown that the main factor of stabilization of the structure is hydrogen bonds. The conditions of three‐component polymer‐colloid system are practically independent of the order of component mixing. The spontaneous formation of polymer‐colloid complexes between chemically complementary polymers and small dispersed particles is considered as the main reason for the abnormally high binding ability of colloid particles to the polymer‐polymer complex.
Self‐assembling complexes with magnetic properties
Authors: Poux Sandrine , Thierry Annette , Rochas Cyrille , Green Mark M. , Guenet Jean‐Michel
Published: November 2003

The magnetic properties and the nucleation capability of a self‐assembling bicopper complex are reported. Attention is focused on the effect of the chirality of the bicopper complex. Comparison is made between the racemic mixture and the right‐handed enantiomer.
Wettability of acrylate copolymer surfaces after ageing in water
Authors: Grohens Yves , Ulvé Stephane , Vallée‐Réhel Karine , Péron Jean Jacques , Haras Dominique
Published: November 2003

Contact angle measurements (captive bubble and sessile drop techniques) were used to determine the surface energy of several acrylic based polymers at the early stage of immersion (t0) in pure and salt water or after several days (tx). The sessile drop technique using various liquid probes allows the calculation of the dispersive, acid and basic components of the surface energy. Significant differences of wettability are observed between the polymers at t0 which tend to remain after immersion along with a general increase of the surface hydrophilicity. The same trend is observed by the “in‐situ” captive bubble technique. The surfaces become more hydrophilic with a final contact angle, θ, ranging from 110 to 150 ± 3° in pure water and 130 to 150 ± 4° in 0,51 M salt water. The modifications of surface energy between t0 and tx are not only dependent on water diffusion. One assumption is that the degree of swelling of the immersed surface layer along with the particular dynamics resulting from a surface gel‐like structure are significant factors in the measured surface thermodynamics.