bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolism and DNA binding of the environmental pollutant 6‐nitrochrysene in primary culture of human breast cells and in cultured MCF‐10A, MCF‐7 and MDA‐MB‐435s cell lines
Authors: Boyiri Telih , Leszczynska Joanna , Desai Dhimant , Amin Shantu , Nixon Daniel W. , El‐Bayoumy Karam
Published: September 2002

The environmental pollutant 6‐nitrochrysene (6‐NC) is a potent mammary carcinogen in the rat. To determine if the results obtained in 6‐NC‐treated rodents can be applicable to humans, we examined its metabolic activation in primary cultures of human breast cells prepared from tissues obtained from reduction mammoplasty from 3 women and in a cultured, immortalized human mammary epithelial cell line (MCF‐10A), as well as estrogen‐dependent (MCF‐7) and estrogen‐independent (MDA‐MB‐435s) human breast cancer cell lines. Metabolites identified following 24 hr incubations of [3H]6‐NC (2.5, 5.0 and 10 μM) with human breast cells were derived from ring‐oxidation (trans‐1,2‐dihydroxy‐1,2‐dihydro‐6‐nitrochrysene [1,2‐DHD‐6‐NC]) and nitro‐reduction (6‐aminochrysene [6‐AC]); chrysene‐5,6‐quinone (C‐5,6‐Q) was also detected. Levels of metabolites (pmol/mg protein) varied greatly depending on the concentration of 6‐NC and the individual breast tissue used; 1,2‐DHD‐6‐NC, ranged from not detected to 15.6 ± 1.0; 6‐AC, from 11.5 ± 4.0 to 155 ± 10.2; C‐5,6‐Q, from 18.3 ± 10.8 to 196.7 ± 15.4. Qualitatively similar metabolic profiles were obtained upon incubation of [3H]6‐NC with MCF‐10A, MCF‐7 and MDA‐MB‐435s. We also detected 1,2‐dihydroxy‐6‐aminochrysene (1,2‐DH‐6‐AC; ranged from not detected to 50.4 ± 9.8). Some of the metabolites identified in our study are known to be proximate carcinogenic forms of 6‐NC in rodents. MCF‐7 was the most efficient cell line in catalyzing 6‐NC to genotoxic metabolites, and we demonstrated that the major DNA adduct is chromatographically identical to that found in the mammary gland of rats treated by gavage with 6‐NC and that obtained from the incubation of [3H]1,2‐DHD‐6‐NC with MCF7 cells or from nitro‐reduction of 1,2‐DHD‐6‐NC in the presence of 2′‐deoxyguanosine 5′‐monophosphate in vitro. This is the first report to demonstrate the ability of human breast cells, MCF‐10A, and breast cancer cell lines to activate 6‐NC to metabolites that can damage DNA. © 2002 Wiley‐Liss, Inc.
Development of HLA‐A2402/Kb transgenic mice
Authors: Gotoh Masashi , Takasu Hideo , Harada Kenji , Yamaoka Takashi
Published: September 2002

HLA‐transgenic mice have been developed to facilitate studies of HLA‐restricted cytotoxic responses, e.g., for the identification of immunodominant HLA‐restricted CTL epitopes and the optimization of peptide or DNA vaccine constructs for human use. We have developed HLA‐A2402/Kb‐transgenic mice expressing chimeric human (α1 and α2 domains of HLA‐A2402) and mouse (α3, transmembrane and cytoplasmic domains of H‐2Kb) class I molecules. Immunization of these HLA‐A2402/Kb‐transgenic mice with various known HLA‐A24‐restricted immunodominant cancer CTL epitope peptides derived from gp100, MAGE‐1, MAGE‐3, Her2/neu, CEA and TERT induced HLA‐A24‐restricted, peptide‐specific CTLs. Using these transgenic mice, we identified a novel HLA‐A24‐restricted CTL epitope, PSA152–160, encoded by human prostate‐specific antigen. Staining with HLA tetramers showed that the cytotoxic activity induced by immunizing with PSA152–160 in HLA‐A2402/Kb transgenic mice was HLA‐A2402‐restricted and CD8‐dependent. Therefore, PSA152–160 might be a candidate peptide for vaccination of HLA‐A24+ patients with prostate cancer. Our results suggest that HLA‐A2402/Kb transgenic mice might be useful in the search for HLA‐A24‐restricted CTL epitopes functioning as human cancer antigens and for the development of peptide‐based cancer immunotherapy. © 2002 Wiley‐Liss, Inc.
Expression of N‐terminally truncated isoforms of CDP/CUX is increased in human uterine leiomyomas
Authors: Moon Nam Sung , Rong Zeng Wendy , Premdas Peter , Santaguida Marianne , Bérubé Ginette , Nepveu Alain
Published: September 2002

Genetic analyses and mRNA expression studies have implicated CUTL1 as a candidate tumor‐suppressor gene in uterine leiomyomas and breast cancers. However, modulation of CDP/Cux, the protein encoded by CUTL1, does not agree with this notion. The activity of CDP/Cux, which is the DNA binding subunit of HiNF‐D, was upregulated as normal cells progressed into S phase and constitutively elevated in several tumor cell lines. Activation of CDP/Cux at the G1/S transition involved the proteolytic processing of the protein to generate a shorter isoform. Uterine leiomyomas represent a unique reagent for molecular analysis because they are resected as homogenous tumor tissue together with the adjacent normal myometrium and they are often very large. In the present study, proteins were isolated from 16 pairs of matched tumors and adjacent myometrium and analyzed by Western blot and electrophoretic mobility shift assays. Strikingly, in 11/16 tumors, the steady‐state level of small CDP/Cux isoforms was increased compared to normal control tissue. Where tested, a corresponding increase in CDP/Cux stable DNA binding activity was observed. DNA sequencing analysis of CUTL1 cDNAs from 6 leiomyomas, including 4 with LOH of CUTL1, did not reveal any gross rearrangement or point mutations. Altogether these findings suggest that CUTL1 is probably not the tumor suppressor on 7q22. Moreover, the frequent increase in smaller CDP/Cux isoforms indicates that molecular events associated with the truncation of CDP/Cux proteins may be selected in uterine leiomyomas. © 2002 Wiley‐Liss, Inc.
A population‐based familial aggregation analysis indicates genetic contribution in a majority of renal cell carcinomas
Authors: Gudbjartsson Tómas , Jónasdóttir Thora J. , Thoroddsen Ásgeir , Einarsson Gudmundur V. , Jónsdóttir Gudrún M. , Kristjánsson Kristleifur , Hardarson Sverrir , Magnússon Kjartan , Gulcher Jeffrey , Stefánsson Kári , Ámundadóttir Laufey T.
Published: September 2002

The etiology of RCC is incompletely understood and the inherited genetic contribution uncertain. Although there are rare mendelian forms of RCC stemming from inherited mutations, most cases are thought to be sporadic. We sought to determine the extent of familial aggregation among Icelandic RCC patients in general. Medical and pathologic records for all patients diagnosed with RCC in Iceland between 1955 and 1999 were reviewed. This included a total of 1,078 RCC cases, 660 males and 418 females. With the use of an extensive computerized database containing genealogic information on 630,000 people in Iceland during the past 11 centuries, several analyses were conducted to determine whether the patients were more related to each other than members drawn at random from the population. Patients with RCC were significantly more related to each other than were subjects in matched groups of controls. This relatedness extended beyond the nuclear family. RRs were significantly greater than 1.0 for siblings, parents and cousins of probands. RRs were 2–3 for first‐degree relatives and 1.6 for third‐degree relatives. The risk of RCC is significantly higher for members of the extended family of an affected individual, as well as the nuclear family. Our results indicate that germline mutations are significantly involved in what has been defined as sporadic RCC. © 2002 Wiley‐Liss, Inc.
ICAM‐1 expression and the soluble ICAM‐1 level for evaluating the metastatic potential of gastric cancer
Authors: Maruo Yukinobu , Gochi Akira , Kaihara Akihiko , Shimamura Hiroshi , Yamada Takatoshi , Tanaka Noriaki , Orita Kunzo
Published: September 2002

ICAM‐1 plays an important role in cell–cell and cell–extracellular matrix interactions, especially tumor invasion and cytotoxicity of lymphocytes. In the present study, the relationship between metastasis of gastric cancer and ICAM‐1 expression by cancer cells or the serum level of s‐ICAM‐1 was (s‐ICAM‐1) was examined. ICAM‐1 was detected by immunohistochemic staining in 49.0% of 108 patients with gastric cancer. The ICAM‐1 expression rate was higher at a more advanced stage, based on lymph node metastasis, being 46.9% in node‐negative and 56.1% in node‐positive cases. In patients with liver metastasis, the rate was 90.9%, while it was 43.3% in patients without liver metastasis (p < 0.05). The serum s‐ICAM‐1 level was 262.1 ng/ml (median 205.5, range 176.0–271.0) in healthy subjects and 391.5 ng/ml (median 317.5, range 148.7–1,768.0) in gastric cancer patients (p < 0.001). The serum s‐ICAM‐1 level was significantly higher in patients with liver metastasis than in patients without liver metastasis (p < 0.0001). In addition, positive ICAM‐1 expression cases had significantly higher s‐ICAM‐1 levels than negative ones, 408.9 ± 188.4 and 308.1 ± 88.1 ng/ml, respectively. These results suggested that ICAM‐1 was overexpressed in cancer cells and released as s‐ICAM‐1, which would promote hematogenous metastasis by suppressing local anticancer immunity. © 2002 Wiley‐Liss, Inc.
Inflammation and cancer, the mastocytoma P815 tumor model revisited: Triggering of macrophage activation in vivo with pro‐tumorigenic consequences
Authors: Kamate Caroline , Baloul Samia , Grootenboer Sabine , Pessis Eric , Chevrot Alain , Tulliez Micheline , Marchiol Carmen , Viguier Mireille , Fradelizi Didier
Published: September 2002

Subcutaneous in vivo injections of cells of the mastocytoma line P815 in syngenic DBA/2 mice induce locally fast growing solid tumors. These have been used extensively as a cancer model to analyze and manipulate the relationship between tumor cells and host's immune defenses. We report that progression of P815 tumors in vivo was accompanied by a burst (Days 5–7) of local inflammatory cells recruitment and angiogenesis observed histologically, corroborated in vivo by MRI with gadolinium, overtranscription of macrophage activation marker genes, secretion of TNF‐α by regional lymph node cells and concomitant systemic inflammation. No substantial overtranscriptions of either VEGF or IL‐10 or TGF‐β genes were observed. Induction of COX‐2 gene was a late event. To establish a possible relationship between the tumor‐induced local, regional and systemic increase of pro‐inflammatory mediators and progression of tumors in vivo, we carried out experiments deliberately modulating the inflammatory status of the recipient animals. Pretreatment of recipient animals by i.p. injection of thioglycolate accelerated P815 tumor growth. At the opposite, treatment of mice with either a COX‐1 + COX‐2 inhibitor (aspirin, 1 mg/day/mouse) or a specific COX‐2 inhibitor (celecoxib, 0.13 mg/day/mouse) for 2 weeks after injection of tumor cells, significantly reduced the size and growth rate of tumors compared to control mice. Experiments carried out in vitro indicated that peritoneal macrophages from untreated animals were strongly activated by live P815 cells and by P815 membrane preparations. The tumor‐induced inflammatory reaction could establish a local micro environment favoring tumor progression. The P815 tumor model might be helpful to recognize important factors controlling host/tumor relationship. © 2002 Wiley‐Liss, Inc.
Progenipoietin‐generated dendritic cells exhibit anti‐tumor efficacy in a therapeutic murine tumor model
Authors: Björck Pia , Lie Wen‐Rong , Woulfe Susan L. , Klein Barbara K. , Olson Walter , Storkus Walter J.
Published: September 2002

Progenipoietin (ProGP‐4) is a chimeric molecule, exhibiting both Flt‐3 and granulocyte‐colony stimulating factor (G‐CSF) receptor agonist activities. Subcutaneous administration of ProGP‐4 to BALB/c mice at a dose of 40–100 μg/day for up to 12 consecutive days induces both CD11c+ dendritic cells (DCs) and CD11c−/CD11b+ granulocytes in spleen, blood and lymph nodes of treated animals. Peak numbers of all cell populations were observed on day 7 of treatment, with CD11c+ DCs representing approximately 8% of total splenocytes at that time. Approximately 40–50% of these CD11c+ cells were also able to endocytose and process the exogenous fluorescent antigen DQ‐BSA. As a test of their therapeutic utility, freshly prepared CD11c+ DCs were pulsed with a defined tumor‐associated peptide epitope (murine p53232–240) and injected as a vaccine into BALB/c mice bearing day 7 established CMS4 sarcomas. Similarly prepared DCs were injected again 1 week later. Based on our results, we conclude that (i) both peptide‐pulsed CD11c+ DCs (harvested directly from ProGP‐4 treated mice) and pulsed bone marrow‐derived DCs effectively slow the growth of or mediate the regression (in 25 of 89 [28%] cases) of CMS4 tumors, and (ii) nonpulsed DCs mediated minimal or no therapeutic effect. These data support the ability of ProGP‐4 to enhance the peripheral frequencies of DCs that exhibit therapeutic efficacy when applied as a vaccine to treat tumor‐bearing animals. © 2002 Wiley‐Liss, Inc.
Concordance of allelic imbalance profiles in synchronous and metachronous bilateral breast carcinomas
Authors: Imyanitov Evgeny N. , Suspitsin Evgeny N. , Grigoriev Maxim Yu. , Togo Alexandr V. , Kuligina Ekatherina Sh. , Belogubova Evgeniya V. , Pozharisski Kazymir M. , Turkevich Elena A. , Rodriquez Carmen , Cornelisse Cees J. , Hanson Kaido P. , Theillet Charles
Published: September 2002

Bilateral breast cancer (biBC) is a common form of breast cancer; however, it has not been subjected to systematic comparative genetic studies. We allelotyped 28 biBCs on 14 chromosomal arms, addressing 2 lines of questions: (i) does comparison of genetic profiles disclose contralateral metastases misdiagnosed as second primaries? and (ii) do shared environmental and host factors drive the development of true biBC along similar genetic routes? Allelotyping provided unambiguous proof for distinct clonality in 23 of 28 cases. In another 4 biBCs, the genotyping data did not exclude the hypothesis of metastatic spread, whereas clinical and histologic data were in favor of bilaterality. Thus the question of clonality remained open only for 1 case, in which the paired tumors shared both histologic features and allelotypes. We conclude that the vast majority if not all biBCs are of independent clonal origin. Next, we assessed the similarity of genetic pathways in distinct categories of biBC. It was assumed that the coexistence of allelic imbalance (AI) in 1 tumor and retention of heterozygosity (N) in the contralateral neoplasm corresponds to the distinct genetic profiles, whereas the remaining combinations (AI/AI or N/N) suggest a match of allelic status for a given polymorphic marker. When these allelic matches were pooled, it turned out that synchronous biBC displayed a significantly higher similarity score than metachronous biBC (64/77 [83%] vs. 162/267 [61%]; p = 0.0003). In addition, an increased similarity of allelic profiles was observed in the premenopausal biBC (76/101 [75%]) compared with postmenopausal cases (111/173 [64%]) or tumor pairs separated by the onset of menopause (39/70 [56%]; p = 0.014). Overall, our data suggest that sharing natural histories of the disease, which is more evident in synchronous and/or premenopausal forms of biBC, may result in a similarity of molecular portraits in bilateral breast tumors. © 2002 Wiley‐Liss, Inc.
A synthetic matrix metalloproteinase inhibitor prevents squamous carcinoma cell proliferation by interfering with epidermal growth factor receptor autocrine loops
Authors: O‐Charoenrat Pornchai , Rhys‐Evans Peter , Eccles Suzanne
Published: September 2002

Head and neck squamous cell carcinoma (HNSCC) is characterized by its capacity to invade adjacent tissues and to metastasize locoregionally. Evidence suggests that matrix metalloproteinases (MMPs) may play a causal role in HNSCC progression. While evaluating the role of MMPs in the invasion process, we made the surprising observation that a broad‐spectrum MMP inhibitor, (marimastat, BB2516), inhibited the growth in vitro of some HNSCC cell lines. This inhibitory effect was only found in HNSCC cell lines overexpressing epidermal growth factor receptors. The effects of the MMP inhibitor could be reversed by adding exogenous c‐erbB ligands, suggesting that the phenomenon may be related to autocrine ligand processing. This hypothesis was supported by the finding that the growth‐inhibitory effect of marimastat was directly related to its ability to prevent the release of major c‐erbB ligands including transforming growth factor‐α, betacellulin and heregulin β1 from HNSCC. Marimastat was also found to potentiate the cytotoxic effects of cisplatin both in vitro and in vivo. Our results indicate that the cleavage of several c‐erbB ligands from membrane‐anchored precursors requires MMP activity. We conclude that MMP inhibitors could prevent tumor progression not only by inhibiting invasion and angiogenesis, as previously shown, but also by their ability to inhibit autocrine signaling through the c‐erbB receptors. Clinical trials to test this hypothesis in HNSCC should be considered. © 2002 Wiley‐Liss, Inc.
Etude comparative de la disponibilité de l'eau en irrigation goutte à goutte
Authors: Ould Mohamed El‐Hafedh A.V. , Daghari H. , Maalej M.
Published: September 2002

Dans le but de déterminer la meilleure combinaison entre période et durée d'irrigation pour différents écartements inter‐goutteurs, nous avons essayé d'analyser la disponibilité de l'eau au sein de la zone racinaire d'une culture de tomate irriguée à l'aide d'une rampe de goutteurs débitant chacun 4 l h−1. Trois écartements ont été étudiés à savoir 30, 50 et 70 cm.

Lorsqu'on a pris une durée d'arrosage systématique de 4h30mn, nous avons observé à la fin des irrigations des teneurs en eau volumiques moyennes dépassant la capacité au champ pour les trois écartements. En effet, à l'examen de l'évolution des teneurs en eau au sein du bulbe, il est remarqué que la teneur en eau à la capacité au champ a été atteinte après 25 minutes, 50 minutes et deux heures respectivement pour 30, 50 et 70 cm. Mais l'humidification de toute la ligne de culture n'a été observée qu'après des temps respectifs d'une heure, deux heures et quatre heures (Ould Mohamed El‐Hafedh et al., 2000).

Les irrigations ont été reprises avec ces durées réduites (une heure, deux heures et quatre heures respectivement pour les écartements 30, 50 et 70 cm) en vue d'évaluer et comparer les consommations en eau de la culture sous les différents traitements.

Dans le cas de l'irrigation d'une durée de 4h30mn, la période séparant deux arrosages successifs a été de cinq, quatre et trois jours respectivement pour les écartements 30, 50 et 70 cm. Pour les irrigations des durées réduites, on a constaté qu'il est impératif d'irriguer après trois jours pour les deux écartements 50 et 70 cm et après deux jours pour l'écartement 30 cm.

En comparant les consommations en eau pour les durées réduites et la durée systématique de 4h30mn, on a observé une économie d'eau de l'ordre de 20, 15 et 5% respectivement pour 30, 50 et 70 cm d'écartement. D'autre part, la comparaison entre les durées réduites montre que la plus importante économie en eau a été réalisée avec 50 cm d'écartement. Copyright © 2001 John Wiley & Sons, Ltd.
Conjunctive use of surface and groundwater: overview and perspective
Authors: de Wrachien Daniele , Fasso Costantino A.
Published: September 2002

The world's fresh water resources are unequally distributed both in time and in space. Until recently water resource management focused on reallocating water to when and where it was required, a supply‐side or fragmented approach. Nowadays there are signs that water resource availability is dwindling—due to both population growth and increased per capita water use—and ecosystems are being damaged. To face this challenge a new holistic approach is needed. This approach includes the integrated or conjunctive use of surface and groundwater resources and takes account of social, economic and environmental factors. Moreover, it recognizes the importance of water quality issues.

In this context, the paper examines the main aspects and problems concerned with the planning, design, construction and management of conjunctive use of surface and subsurface water resources, along with its environmental impacts and constraints to sustainable development. The importance and role of research thrust, technology transfer, institutional strengthening, effective partnerships between governments and stakeholders, and sound financial frameworks are also examined. Finally, the challenges and benchmarks for future actions that the scientific community and planners have to face and deal with, are briefly outlined. Copyright © 2002 John Wiley & Sons, Ltd.
Stability and wage acceleration in macroeconomic models of cyclical growth
Authors: Bergstrom A. R.
Published: September 2002

This paper is concerned with the stability of macroeconomic models in which there is no long‐run trade‐off between unemployment and inflation, because of a wage adjustment equation based on the NAIRU concept. It is shown, for a simple theoretical model and for the Bergstrom–Nowman–Wymer continuous‐time macro‐econometric model of the UK, that there is a bounded range of positive values of the wage acceleration parameter (determining the effect of labour demand on wage acceleration) for which the steady state is asymptotically stable. Then, each model generates damped cycles about a path converging to the steady‐state neoclassical growth path. Copyright © 2001 John Wiley & Sons, Ltd.
Descriptive econometrics for non‐stationary time series with empirical illustrations
Authors: Phillips Peter C. B.
Published: September 2002

Recent work by the author on methods of spatial density analysis for time series data with stochastic trends is reviewed. The methods are extended to include processes with deterministic trends, formulae for the mean spatial density are given, and the limits of sample moments of non‐stationary data are shown to take the form of moments with respect to the underlying spatial density, analogous to population moments of a stationary process. The methods are illustrated in some empirical applications and simulations. The empirical applications include macroeconomic data on inflation, financial data on exchange rates and political opinion poll data. It is shown how the methods can be used to measure empirical hazard rates for inflation and deflation. Empirical estimates based on historical US data over the last 60 years indicate that the predominant inflation risks are at low levels (2–6%) and low two‐digit levels (10–12%), and that there is also a significant risk of deflation around the −1% level. Copyright © 2001 John Wiley & Sons, Ltd.
European integration and monetary transmission mechanisms: the case of Italy
Authors: Juselius Katarina
Published: September 2002

The focus in this paper is on the monetary transmission mechanism in Italy and how it has changed with the increased independence of the Italian Central Bank and the increasingly fixed exchange rates of the ERM. The sample period 1974–1994 is divided into two parts approximately corresponding to the different systems. Based on a VAR model for money, income, prices, and interest rates the cointegration properties of the data in nominal and real terms are analysed. Long‐run price homogeneity is empirically rejected and the economic and econometric consequences for a real money analysis are described. Altogether we find little evidence that the use of M2 and the short interest rate as intermediate targets has effectively controlled price inflation in this period. Copyright © 2001 John Wiley & Sons, Ltd.
An I(2) analysis of inflation and the markup
Authors: Banerjee Anindya , Cockerell Lynne , Russell Bill
Published: September 2002

An I(2) analysis of Australian inflation and the markup is undertaken within an imperfect competition model. It is found that the levels of prices and costs are best characterized as integrated of order 2 and that a linear combination of the levels (which may be defined as the markup) cointegrates with price inflation. From the empirical analysis we obtain a long‐run relationship where higher inflation is associated with a lower markup and vice versa. The impact in the long run of inflation on the markup is interpreted as the cost to firms of overcoming missing information when adjusting prices in an inflationary environment. Copyright © 2001 John Wiley & Sons, Ltd.
Finite sample improvements in statistical inference with I(1) processes
Authors: Marinucci D. , Robinson P. M.
Published: September 2002

Robinson and Marinucci (1998) investigated the asymptotic behaviour of a narrow‐band semiparametric procedure termed Frequency Domain Least Squares (FDLS) in the broad context of fractional cointegration analysis. Here we restrict discussion to the standard case when the data are I(1) and the cointegrating errors are I(0), proving that modifications of the Fully Modified Ordinary Least Squares (FM‐OLS) procedure of Phillips and Hansen (1990) which use the FDLS idea have the same asymptotically desirable properties as FM‐OLS, and, on the basis of a Monte Carlo study, find evidence that they have superior finite‐sample properties. The new procedures are also shown to compare satisfactorily with parametric estimates. Copyright © 2001 John Wiley & Sons, Ltd.
Modelling UK inflation, 1875–1991
Authors: Hendry David F.
Published: September 2002

UK inflation has varied greatly in response to many economic policy and exchange‐rate regime shifts, two world wars and two oil crises, as well as legislative and technological changes. Inflation is modelled as responding to excess demands from all sectors of the economy: goods and services, factors of production, money, financial assets, foreign exchange, and government deficits. Equilibrium‐correction terms are developed for each of these over the sample. Indicator variables and commodity prices capture turbulent years. Variables representative of most theories of inflation matter empirically, yielding an eclectic model inconsistent with any ‘single‐cause’ explanation. Copyright © 2001 John Wiley & Sons, Ltd.
Influence of cosolvents and in situ forming hydroxyapatite on the mechanical characteristics of collagen films
Authors: Ho Hsiu‐O , Tsai Tsuimin , Liu Chia‐Ming , Sheu Ming‐Thau
Published: September 2002

Collagen was processed into films in mixtures containing various ratios of water, propylene glycol, and ethanol. An experimental mixture design was applied to characterize the effects of individual solvents and their interactions on the mechanical properties of collagen films. Scanning electron microscopy (SEM) was used to examine the surface properties of collagen films. The ultimate tensile strength (UTS) and related characteristics of collagen films were also evaluated with dynamic mechanical analysis. The effect of in situ forming hydroxyapatite (HAP) within collagen films at a concentration of 10 mM on the physical characteristics of these films was evaluated by the same methods. With X‐ray and SEM examinations, it was confirmed that HAP was formed inside the collagen film. However, the UTS of collagen films without HAP was 4–5 times higher than that with HAP. This was probably due to the discontinuity of the film structure caused by HAP in the collagen films. The results of a statistical analysis of the experimental design revealed the influence of the solvent mixtures on the mechanical properties of the collagen films with and without HAP, showing similar responses for the UTS and modulus of elasticity. Both parameters showed a maximal response in the solvent range containing a lower percentage of ethanol with the desired percentage of propylene glycol to plasticize the collagen films. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 22–29, 2002
Behavior of dense and porous hydroxyapatite implants and tissue response in rat femoral defects
Authors: Andrade J.C.T. , Camilli J.A. , Kawachi E.Y. , Bertran C.A.
Published: September 2002

Porous and dense hydroxyapatite cylinders (PHA and DHA) were implanted into cavities produced in rat femora and the sites of implantation were examined at different times over a period of 24 weeks by microradiologic and histological techniques. Microradiographs showed the presence of a layer of trabecular bone around the implants, which became more radiopaque and thinner along the experimental time. The microradiologic methodology used was suitable for the evaluation of the interface between hydroxyapatite and newly formed bone in nondecalcified materials. Microscopic observations showed that young bone grew over the surface of both types of implants after 1 and 2 weeks of surgery and that bone also grew inside PHA implants. Progressive bone absorption was observed in both types of implants after the fourth week. A layer of fibrous tissue was formed in the interface between new bone and DHA. Mature bone with haversian systems surrounded DHA implants and filled the pores of PHA implants throughout the experimental period. The pores of PHA implants were smaller than those commonly reported, which should have been a disadvantage, although it was observed that the extra cellular fluid induced disintegration of the ceramic granules, allowing the gradual growth of bone tissue into the spaces among them, without the interposition of fibrous tissue. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 30–36, 2002
Raman and IR studies on adsorption behavior of adhesive monomers in a metal primer for Au, Ag, Cu, and Cr surfaces
Authors: Suzuki Masako , Yamamoto Masato , Fujishima Akihiro , Miyazaki Takashi , Hisamitsu Hisashi , Kojima Katsunori , Kadoma Yoshinori
Published: September 2002

6‐[N‐(4‐vinylbenzyl)propylamino]‐1,3,5‐triazine‐2,4‐dithione (VBATDT) and 10‐methacryloyloxydecyl dihydrogen phosphate (M10P) are functional monomers used for the surface treatment of dental alloys. The aim of our study was to clarify the role of a commercial metal primer containing both the monomers in adhesion between resin and various dental metals on a molecular level. We used surface‐enhanced Raman scattering (SERS) and infrared reflection absorption (IRA) spectroscopy. An SERS measurement was performed with a 647 nm laser line for a mixture of aqueous Au colloid and the primer. IRA spectra were taken for cast films of the primer on Au, Ag, Cu, and Cr surfaces as a function of rinse time, and for self‐assembled monolayer (SAM) films from dilute mixed solution of VBATDT and M10P. These spectra indicate that VBATDT in the primer is mainly chemisorbed on Au, Ag, and Cu surfaces with respect to thickness, whereas only M10P is adsorbed on Cr. We also examined the tensile bond strengths between resin and Au, Ag, Cu, and Cr plates treated by VBATDT, with and without M10P, and found that VBATDT effectively promotes the bond strength between resin and the metals except for Cr, whereas M10P is effective only for Cr. These adhesion characteristics are consistent with the chemisorbed species on each metal surface as shown in the spectroscopic evidence. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 37–45, 2002
The influence of culture conditions on extracellular matrix proteins synthesized by osteoblasts derived from rabbit bone marrow
Authors: Cornet François , Anselme Karine , Grard Thierry , Rouahi Myriam , Noël Benoit , Hardouin Pierre , Jeanfils Joseph
Published: September 2002

The influence of culture conditions on the extracellular matrix (ECM) protein expressions of rabbit bone marrow stromal cells has been studied. The focus was on the effects of two kinds of sera, fetal calf serum (FCS) and Ultroser®, on cells treated with dexamethasone. The induction of osteoblastic differentiation by dexamethasone addition is confirmed, particularly when cells are cultured in FCS. Bone marrow stromal cells produce alkaline phosphatase positive CFU‐F and produce ECM with some mineralized nodules. Analysis by means of two‐dimensional gel electrophoresis showed important changes in the composition of ECM proteins after dexamethasone treatment. Overexpression, underexpression, and new synthesized proteins were observed. The most significant modification was linked to the synthesis of four new proteins visible in the acidic area with a low molecular weight of around 17 kDa. These proteins did not correspond to those ECM proteins known to be induced by dexamethasone. Moreover, the effect of dexamethasone on osteoblastic differentiation induction appears very limited when cells are cultured in Ultroser® compared to FCS. The protein pattern with Ultroser® is different to that obtained with FCS. Cells cultured in Ultroser® synthesized no new protein. The different behavior of cells according to the type of medium used is discussed in terms of the osteogenic factors present in the two different sera. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 400–407, 2002
Surface structure study of biological calcium phosphate apatite crystals from human tooth enamel
Authors: Brès E. F. , Hutchison J. L.
Published: September 2002

A surface‐structure study of human tooth enamel crystals has been carried out by high‐resolution electron microscopy (HREM). The surfaces of several crystals have been examined and the surfaces of a single crystal are described here. The observations made on this crystal are similar to the observations made on the other crystals, although the difference of morphology in the crystals observed indicates that the growth control by matrix proteins takes only place on the {011¯0} surfaces of the crystals. The crystal described here is oriented along the [112¯0] direction, and the following surfaces have been analyzed: (11¯00), (011¯1), (01¯11) and (0001). A subsurface reconstruction is observed just below the surface of the crystal not bonded to the matrix and lying above the supporting film. Observation of the matrix surrounding the crystal shows the existence of poorly crystalline phases with a structure close to that of hydroxyapatite (OHAP). Finally, a comparison of the images of the (011¯0) surface with computer‐simulated images calculated for several models of the OHAP surface structure shows that the surface itself is stoichiometric and contains both calcium and phosphate groups. The knowledge of the binding sites of proteins on biomineral crystals such as the ones found in human tooth enamel is of prime importance for the understanding of their growth process. In this study, the first structure determination of the surface of human tooth enamel crystals is presented. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 433–440, 2002
Model of the mechanism of Ca loss by bones under microgravity and earth conditions
Authors: Suvorova Elena I. , Buffat Philippe A.
Published: September 2002

A comparative characterization of crystal structure, morphology, sizes, and orientation in Ca phosphate precipitation from aqueous solutions, the mineral phase in bones, and mineral deposits on cardiac valves has been performed by high‐resolution transmission electron microscopy to model possible mechanisms of Ca loss by bones. Physiological changes occurring in organisms can lead to deep perturbations of the natural calcium phosphate supersaturation and its local distribution, which in turn influences the phase composition, morphology, and organization of the mineral phase. Formation of crystals with larger size or of two distinct phases instead of the single hydroxyapatite one can result in the deterioration of the Ca balance in bone and tissue destruction as well as the possible misorientation (or spread of orientation) between HAP crystals newly formed in the bone. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 424–432, 2002
The effect of the monomer‐to‐powder ratio on the material properties of acrylic bone cement
Authors: Belkoff Stephen M. , Sanders Janis C. , Jasper Louis E.
Published: September 2002

The procedure percutaneous vertebroplasty consists of injecting polymethylmethacrylate cement into vertebral bodies for the treatment of osteoporotic compression fractures and tumors of the spine. Clinicians practicing vertebroplasty commonly alter the mixture of monomer‐to‐powder recommended by the manufacturer in an effort to decrease viscosity and increase the working time. The purpose of the current study was to measure the effect of varying the monomer‐to‐powder ratio on the compressive material properties (compressive modulus, yield stress, and ultimate compressive strength) of the cement Simplex P (Stryker‐Howmedica‐Osteonics, Rutherford, NJ). Cylindrical specimens were prepared using monomer‐to‐powder ratios of 0.45 to 1.00 mL/g and tested in compression. Peak compressive material properties occurred at the mixture ratio recommended by the manufacturer (0.5 mL/g) but decreased as the ratio of monomer to powder was increased. The material properties of specimens cured for 1 hour were significantly less than those for specimens cured for 24 hours. The monomer‐to‐powder ratio affects the compressive material properties of cement. The clinical significance of these results with respect to vertebroplasty is yet to be determined. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 396–399, 2002
Molecular mechanical models for organic and biological systems going beyond the atom centered two body additive approximation: aqueous solution free energies of methanol and N‐methyl acetamide, nucleic acid base, and amide hydrogen bonding and chloroform/water partition coefficients of the nucleic acid bases
Authors: Cieplak Piotr , Caldwell James , Kollman Peter
Published: September 2002

We have developed a methodology to derive RESP charges for molecular mechanical models that include “lone pairs” on lone‐pair donor sites and atom‐centered polarizabilities. This approach uses a very high level ab initio cc‐pVTZ basis set,1 where the multipole moments of the molecules are as accurate as possible. The partial charges are derived self‐consistently so that the model, whose electrostatic potential comes from both partial charges and induced dipoles, reproduces the quantum mechanical electrostatic potential. We then study the ability of such models to reproduce the aqueous solvation free energy of methanol and N‐methyl acetamide (NMA), the base pair hydrogen bonding of the 26 base pairs analyzed by Hobza et al. and the chloroform/water partition coefficients of the five N‐methyl substituted nucleic acid bases. The base pair H‐bond energies are described as well as the atom centered additive model, after modifying the van der Waals parameter on the NH to give reasonable base pair H‐bond distances. The experimental solvation free energies (gas→water) of methanol and NMA are well described, and the water/CHCl3 partition coefficients are improved over the additive model, without any parameter changes. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1048–1057, 2001
A hybrid QM/MM method employing real space grids for QM water in the TIP4P water solvents
Authors: Takahashi H. , Hori T. , Hashimoto H. , Nitta T.
Published: September 2002

A novel hybrid quantum mechanical (QM)/molecular mechanical (MM) approach that employs the real‐space grids for the QM subsystem is proposed for investigating chemical reactions in an aqueous condensed phase. All of the Hamiltonian matrix elements including electric fields formed by the point charges on MM waters is represented in the real space. Details of the practical implementations are presented. The solute polarization, solvation structure, and the solvation energy of a water are computed, and the results are compared with those obtained by experiments and other QM/MM approaches that used the LCAO basis. It is shown that the real‐space grid QM/MM method is adequate and superior for the description of the polarization of QM water in a water solution as well as in the gas phase. Solvation structures of classical water solvents are also properly reproduced by this method. Further, parallelization of the code is implemented on a distributed memory architecture, and it is demonstrated that the real‐space grid approach is suitable for the high‐performance parallel computing due to the localization of Hamiltonian operations in the real space. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1252–1261, 2001
Multicanonical parallel simulations of proteins with continuous potentials
Authors: Hayryan Shura , Hu Chin‐Kun , Hu Shun‐Yun , Shang Rung‐Ji
Published: September 2002

The determination of the three‐dimensional (3D) structure of a protein or peptide is a very important research problem in biological and medical sciences. Anfinsen's experiments (Science 1973, 181, 223) on renaturation of denatured proteins have shown that the native 3D structure of a (small) protein at low (room) temperatures is uniquely determined by its amino acid sequence, which suggests that it might be possible to determine the 3D structure of a protein from its amino acid sequence by pure computations. As a step toward that goal, in this article we present a simple approach for parallelization of multicanonical Monte Carlo simulations of proteins with continuous potentials. Our method is based on the parallel calculation of the protein energy function. The algorithm is tested by simulated annealing and multicanonical simulations of two small peptides, and known results are reproduced accurately. An acceptable degree of parallelization can be achieved in the simulation of Protein L using up to 30 PCs. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1287–1296, 2001
p21 gene codon 31 arginine/serine polymorphism: Non‐association with endometriosis
Authors: Hsieh Yao‐Yuan , Tsai Fuu‐Jen , Chang Chi‐Chen , Chen Wen‐Chi , Tsai Chang‐Hai , Tsai Horng‐Der , Lin Cheng‐Chieh
Published: September 2002

p21, an important regulator of the cell cycle, acts as a mediator of the growth‐suppressing and ‐promoting functions of p53. We aimed to investigate the association between codon 31 polymorphisms of p21 gene and endometriosis. Women were divided into two groups: endometriosis (n = 102) and nonendometriosis (n = 119). The gene polymorphism for p21 codon 31 involved a base change from AGC to AGA and amino acid changes from serine (Ser) to arginine (Arg). Polymorphisms (Ser homozygotes, heterozygotes, Arg homozygotes) between both groups were detected and compared. Associations between the endometriosis and polymorphisms were evaluated. The results revealed that the distributions of different p21 polymorphisms in both groups were nonsignificantly different. The proportions of Ser homozygote/heterozygote/Arg homozygote in endometriosis and nonendometriois populations were 26.5/48.0/25.5% and 17.6/50.4/31.9%, respectively. We concluded the noncorrelation between the endometriosis and the p21 codon 31 polymorphism. p21 gene codon 31 arginine/serine polymorphism is not a useful marker for prediction of endometriosis susceptibility. J. Clin. Lab. Anal. 15:184–187, 2001. © 2001 Wiley‐Liss, Inc.
Semi‐quantitative analysis of cytokine mRNA expression induced by the herbal medicine Sho‐saiko‐to (TJ‐9) using a Gel Doc system
Authors: Huang Xian‐Xi , Yamashiki Masayoshi , Nakatani Kaname , Nobori Tsutomu , Mase Akihito
Published: September 2002

The RT‐PCR method was employed to determine the cytokine mRNA expression of human peripheral lymphocytes induced by the Japanese herbal medicine Sho‐saiko‐to (TJ‐9). The results showed that the mRNA expression of IL‐12, IL‐1β, IL‐10, TNF‐α, G‐CSF, and IFN‐γ increased after 6 hr in culture. This is the first reported finding that TJ‐9 is an IFN‐γ inducer. Next, cytokine mRNA expression was semi‐quantitatively measured using the Gel Doc system with a CCD camera and then statistically analyzed in order to determine which component of TJ‐9 was the true cytokine inducer. The results showed that the scutellaria root is the main component inducing the cytokines, while the glycyrrhiza root is the secondary component. When the cytokine concentrations in the supernatants of cell cultures were measured by ELISA, the levels of IL‐12, IL‐1β, IL‐10, TNF‐α, and G‐CSF reflected mRNA expression levels in the cell fraction. However, the level of IFN‐γ was below the detectable limit. The effects of various reagents on many different kinds of cytokine mRNA expression could be analyzed objectively in a short time using the Gel Doc system. Many important findings could be demonstrated by this simple, easy, sensitive, and cheap method. After the clinical significance of cytokine analysis is confirmed, this method may become a useful clinical examination tool. J. Clin. Lab. Anal. 15:199–209, 2001. © 2001 Wiley‐Liss, Inc.
Eye movement desensitization and reprocessing (EMDR): Information processing in the treatment of trauma
Authors: Shapiro Francine , Maxfield Louise
Published: September 2002

Eye Movement Desensitization and Reprocessing (EMDR) is an efficacious and efficient treatment for posttraumatic stress disorder (PTSD). This article provides a brief overview of the findings of 20 controlled‐outcome studies and describes Shapiro's Adaptive Information Processing model. This model posits that pathology results when distressing experiences are processed inadequately and hypothesizes that EMDR accelerates information processing, resulting in the adaptive resolution of traumatic memories. A detailed description of the eight phases of treatment highlights the procedures, assumptions, and clinical observations that currently guide EMDR clinical practice. A case study, with an in‐session transcript, illustrates the application of EMDR to address the past events that have laid the groundwork for dysfunction, the present circumstances that elicit distress, and skills acquisition needed for adaptive functioning. © 2002 Wiley Periodicals, Inc. J Clin Psychol/In Session 58: 933–946, 2002.
Psychosocial aspects of the organ transplant experience: What has been established and what we need for the future
Authors: Engle David
Published: September 2002

This article briefly describes the current status and limitations of the organ transplant process that has now become a routine medical procedure. The article discusses how transplantation is not a cure for end‐stage organ disease but an alternative form of treatment with both potential medical and psychosocial problems. Both transplant candidates and recipients encounter psychosocial problems. The article examines how these psychosocial problems affect transplant patients prior to transplant, immediately following surgery, and posttransplant. The psychosocial problems include psychiatric diagnoses, individual and family adjustment and relationship problems, sexual dysfunction, return‐to‐work (RTW) difficulties, and compliance problems and variables related to noncompliance. The article also reviews the special problems of pediatric and adolescent transplant recipients. The need for empirically supported interventions is noted in each of the problem areas. The author outlines problems with previous research studies that hamper solid interpretations of the data, and discusses literature suggesting that the psychosocial problems of transplant candidates and recipients are likely to be underreported. The article concludes with recommendations about the need to switch research efforts toward intervention studies in the problem areas already solidly identified by the literature. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 521–549, 2001
Pain and emotion: New research directions
Authors: Keefe Francis J. , Lumley Mark , Anderson Timothy , Lynch Thomas , Carson Kimi L.
Published: September 2002

Recently, there has been growing interest in the relation between pain and emotion. Numerous recent studies have been conducted in this area. This article provides an introduction to this interesting area by highlighting selected research topics including studies on: stress and pain, negative emotional states and pain, catastrophizing and pain, the fear of pain, emotional regulation processes and pain, the effects of enhancing emotional regulation on pain, and the relation of emotional distress to treatment seeking in persons having pain. The article concludes with a discussion of important directions for future research in this area. © 2001 John Wiley & Sons, Inc. J Clin Psychol 57: 587–607, 2001.