bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro metabolism of mirtazapine enantiomers by human cytochrome P450 enzymes
Authors: Dodd Seetal , Boulton David W. , Burrows Graham D. , De Vane C. Lindsay , Norman Trevor R. 
Published: August 2002

AbstractThe metabolism of mirtazapine enantiomers was investigated in vitro using human lymphoblast microsomes transfected with human cDNA to overexpress either CYP1A2, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 and assayed for mirtazapine enantiomers using a validated chiral method of high‐performance liquid chromatography. (+)‐Mirtazapine was extensively metabolised by CYP2D6 (Km = 9.3 ± 3.3 μmol/l, Vmax = 40.9 ± 7.9 μmol/h/mg, intrinsic clearance = 4.41 l/h/mg). CYP1A2 and CYP3A4 showed low metabolic activity towards (+)‐mirtazapine and (−)‐mirtazapine respectively. Neither CYP2C9 nor CYP2C19 appeared to be involved in the metabolism of the enantiomers of mirtazapine. Copyright © 2001 John Wiley & Sons, Ltd.
The altitudinal distribution of snow algae on an Alaska glacier (Gulkana Glacier in the Alaska Range)
Authors: Takeuchi Nozomu 
Published: August 2002

AbstractThe altitudinal distribution of a snow algal community was investigated on an Alaska glacier (Gulkana Glacier in the Alaska Range) from 1270 to 1770 m a.s.l.. Seven species of snow and ice algae (Chlorophyta and cyanobacteria) were observed on the glacier surface. These species wereChlamydomonas nivalis,Mesotaenium berggrenii,Ancylonema nordenskioldii,Cylindrocystis brébissonii,Raphidonemasp., and two Oscillatoriaceae cyanobacteria. The altitudinal distribution of snow algae was different among the species:Cd. nivaliswas distributed on the middle to upper area,M. berggrenii;A. nordenskioldii, and one Oscillatoriaceae cyanobacterium on the middle to lower area;Raphidonemasp. on the middle area; andCyl. brébissoniiand one Oscillatoriaceae cyanobacterium on the lower area. The total cell concentration and the cell volume biomass of the snow algae ranged from 4·4 × 103to 9·9 × 105cells ml−1and from 33 to 2211 µl m−2respectively. The cell volume biomass changed with altitude; the biomass increased with altitude below 1600 m a.s.l., and decreased above 1600 m a.s.l. The community structure showed thatA. nordenskioldiidominated on the lower part of the glacier, and thatCd. nivalisdominated on the upper part. The species diversity was relatively high at the lowest and middle sites. The pH was 4·7 to 5·3 for snow and 4·9 to 5·7 for ice on the glacier. The altitudinal distribution of snow algae is discussed in terms of the physical and chemical condition of the glacier surface, and is compared with that on a Himalayan glacier. A larger biomass in the snow area on the Alaska glacier than that of the Himalayan glacier is likely due to less frequent snow cover in summer in Alaska. Small amounts of filamentous cyanobacteria on the Alaska glacier may allow washouts of unicellular green algae by running melt water and may cause a different pattern of altitudinal distribution of algal biomass on the ice area from the Himalayan glacier. Copyright © 2001 John Wiley & Sons, Ltd.
The potential role of freshwater luminescence measurements in exploring runoff pathways in upland catchments
Authors: Newson M. , Baker A. , Mounsey S. 
Published: August 2002

AbstractThe forested Coalburn catchment (1·5 km2) in northern England experiences episodic stream acidification. To plan for sustainable management of the plantation forest cycle, an understanding is required of the flow pathways and hydrochemical routing signatures of the organic and mineral soils that make up the source areas for runoff. A tentative mixing model, based on simple water chemistry exists for the major (terrestrial) sources and buffers of acidification; it is being expanded and consolidated by a detailed approach to the organic components of runoff, via sampling and analysis of the luminescence of surface waters at the catchment outlet and in two distinctive feeder streams. Luminescence measurements are presented that permit a simple apportionment of source areas. However, the technique also appears to have potential for identifying differential flow sourcing between the acrotelm and catotelm of intact peat deposits and for clarifying the influence of forest root systems in altering the organic chemistry of infiltrating waters. Applications may include the monitoring and prediction of coloured water events for the water supply industry. Copyright © 2001 John Wiley & Sons, Ltd.
Effect of drought on hydrology and sulphate dynamics in a temperate swamp
Authors: Warren F. J. , Waddington J. M. , Bourbonniere R. A. , Day S. M. 
Published: August 2002

AbstractTemperate wetlands are generally net retainers of sulphate (SO4−2). However, recent research indicates that some wetlands may export SO4−2 during drought conditions. In temperate wetlands, the susceptibility to drought will depend on wetland–stream and groundwater–surface water interactions. Here we present results of summer SO4−2 dynamics in a confined and unconfined stream within a temperate swamp.At the confined transect, the water table levels dropped greatly (−55 cm) and groundwater flow patterns reversed in response to summer drought. Although high porewater SO4−2 concentrations (36·4 mg l−1) were measured, no downstream export of SO4−2 was observed. A SO4−2 mass balance analysis on this stream reach indicated near zero retention. At the unconfined transect, water flowed from the stream to the wetland throughout most of the summer, maintaining relatively high water table levels (−25 cm). Sulphate porewater concentrations were significantly lower (9·2 mg l−1) than in the confined transect. Downstream discharge decreased to zero within this reach during extreme drought conditions, resulting in 100% SO4−2 retention for a three‐week period. Upon rewetting stream SO4−2 levels increased to 161·7 mg l−1 resulting in a large net export of SO4−2. This study demonstrates that while water table position was an important control on SO4−2 dynamics within the wetland, the degree of hydrologic connectivity between the wetland and the stream was the main control on episodic SO4−2 release following summer drought. Copyright © 2001 John Wiley & Sons, Ltd.
Impact on Sahelian runoff of stochastic and elevation‐induced spatial distributions of soil parameters
Authors: Séguis Luc , Cappelaere Bernard , Peugeot Christophe , Vieux Baxter 
Published: August 2002

AbstractTopography controls surface flows, and thereby exerts a significant action on soil formation. At the hillslope scale, infiltrability of the surface horizon varies gradually along the slope. In semi‐arid zones, and especially in the Sahel, runoff is Hortonian and depends mainly on the hydraulic properties of the soil surface horizon (saturated hydraulic conductivity Ks and hydraulic roughness of the soil surface n). Using the fully distributed hydrologic model r.water.fea as an experimentation tool, this paper investigates the effects of various spatial distributions of Ks (deterministic, stochastic or a combination of both, all with an invariant global mean) and related n (taken as fully correlated to Ks) on the outflow of a small catchment representative of Sahelian conditions. In addition to a uniform distribution used as reference, deterministic distributions here consist of linear variations of Ks with elevation. A stochastic component is then added by drawing from a log‐normal distribution with different variation coefficients Cv. Both hypothetical and real rainstorm events are tested.All Ks distributions studied produce hydrographs that are very close to the uniform Ks case when rainfall is long and intense. For most other rain events, runoff increases with Ks variability. Whatever the rainfall event and Cv, outflow is greater when the less infiltrative surfaces are located downhill. The ratio of deterministic to purely stochastic variation is a good indication of the relative importance of the two Ks variation sources for catchment runoff. Given the high local‐scale (stochastic) soil variability typically encountered, only strong catchment‐scale contrasts really deserve to be included in the Ks distribution for runoff modelling of all but insignificant events. Spatial Ks representation can be further simplified down to a uniform distribution, when only a seasonal water yield is the required result. Copyright © 2002 John Wiley & Sons, Ltd.
Consumer insolvency in Australia
Authors: Duns John , Mason Rosalind 
Published: August 2002

AbstractThis paper seeks to identify and assess the features of Australian bankruptcy regulation as they apply to consumer insolvency. Although Australian bankruptcy law makes no explicit recognition of ‘consumer bankruptcy’ as a regulatory target in itself, the Australian legislation nevertheless has a number of features that impact on what would generally be seen to be consumer bankrupts. After providing an outline of the legislative framework within which consumer bankruptcy operates, the paper examines the consumer insolvency aspects of this legislation, together with an assessment of proposed reforms. Some brief comparisons of the ‘consumer’ features of Australian regulation with that of the more fully developed consumer provisions of the Canadian and the United States bankruptcy legislation, are made in order to highlight the Australian position.The Australian Act has historically drawn heavily on English bankruptcy legislation but inevitably Australia has to some extent developed along its own path. Notable is the reasonably vigorous approach to discharge from bankruptcy. The proposed reforms to the Bankruptcy Act, which have followed a detailed consultative process, are largely directed to consumer debtors. Some of these reforms are directed against a perceived debtor abuse of the bankruptcy system. Other reforms, such as increasing the availability of debt agreements, are more generous to insolvent debtors. On the whole the reforms appear to be based more on political than empirical grounds.
Prediction of chemotherapeutic response by collagen gel droplet embedded culture‐drug sensitivity test in human breast cancers
Authors: Takamura Yuuki , Kobayashi Hisayuki , Taguchi Tetsuya , Motomura Kazuyoshi , Inaji Hideo , Noguchi Shinzaburo 
Published: August 2002

AbstractCollagen gel droplet embedded culture‐drug sensitivity test (CD‐DST) is the newly developed in vitro chemosensitivity test that has several advantages over the conventional ones. The aim of the present study is to examine the clinical usefulness of this test in the prediction of response to chemotherapy in breast cancer patients. Seventy patients with primary (n = 45) or locally recurrent (n = 25) breast cancers were recruited, and each patient underwent tumor biopsy before chemotherapy. The biopsy specimens were used for CD‐DST and immunohistological examination of 6 biological markers (P‐gp, erbB2, p53, BCL2, MIB1 and ER‐α). As chemotherapy, cyclophosphamide 600 mg/m2 plus epirubicin 60 mg/m2 q3w (CE, n = 28) or docetaxel 60 mg/m2 q3w (DOC, n = 42) was given. Interpretable results using the CD‐DST assay were obtained from 84.3% (59/70) of tumor specimens studied. Of the 18 tumors diagnosed as CE sensitive by CD‐DST, 15 (83.3%) exhibited a response to CE therapy and none of the 5 tumors diagnosed as CE resistant by CD‐DST exhibited a response to CE therapy. Of the 14 tumors diagnosed as DOC sensitive by CD‐DST, 13 (92.9%) exhibited a response to DOC therapy and only one of the 22 tumors diagnosed as DOC resistant by CD‐DST exhibited a response to DOC therapy. P‐gp expression was found to exhibit a significant (p < 0.05) association with the resistance to CE therapy but not to DOC therapy. Diagnostic accuracy (72.7%) achieved by P‐gp was lower than that (87.0%) achieved by CD‐DST in CE therapy. Expressions of other biological markers (erbB2, p53, BCL2, MIB1 and ER‐α) were not significantly associated with response to CE or DOC therapy. These results demonstrate that CD‐DST can predict the response to CE and DOC therapy with a high accuracy in breast cancer patients and seems to be superior to the conventional predictors. © 2002 Wiley‐Liss, Inc.
Identification of BRCA1 and BRCA2 carriers by allele‐specific gene expression (AGE) analysis
Authors: Montagna Marco , Agata Simona , De Nicolo Arcangela , Menin Chiara , Sordi Gianni , Chieco‐Bianchi Luigi , D'Andrea Emma 
Published: August 2002

AbstractMutations in BRCA1 and BRCA2 genes confer a high risk of breast and ovarian cancer. As such, their identification is essential to reduce the risk of disease in healthy carriers, as well as in carriers who have already developed the disease because they are at increased risk for a second malignancy; moreover, noncarriers of BRCA1 and BRCA2 mutated families can be spared anxiety and unnecessary medical interventions. A number of problems, including large gene size, complex mutational spectra and genetic heterogeneity of the disease, however, make genetic testing labor intensive and often inconclusive. We devised a new mutation detection strategy called AGE (allele‐specific gene expression) analysis that relies on the detection of a “functional effect” of the mutation at the RNA level known as “nonsense‐mediated RNA decay,” thus avoiding several of the problems of BRCA1 and BRCA2 genetic testing. In particular, (i) AGE analysis discriminates among the predisposing genes and identifies mutation carriers with a single RT‐PCR reaction; (ii) it relies on the effect of truncating mutations, which represent the large majority of cases and thus identifies mutation carriers regardless of the specific genomic alteration; and (iii) it is specific for cis‐regulatory mutations that are missed at present by most of the methods. As AGE analysis has the potential to identify most of the BRCA1 and BRCA2 mutation carriers, it can be used as a preliminary screening method, thereby accelerating and increasing the sensitivity of the genetic testing process. Notably, other hereditary diseases whose genetic analysis is hampered by similar problems could benefit from this kind of approach. © 2002 Wiley‐Liss, Inc.
Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer
Authors: Kudoh Kazuya , Ichikawa Yoshihito , Yoshida Sadao , Hirai Misako , Kikuchi Yoshihiro , Nagata Ichiro , Miwa Masanao , Uchida Kazuhiko 
Published: August 2002

AbstractTo define the involvement of p16/CDKN2 and p15/MTS2 tumor‐suppressor genes for response to chemotherapy in primary epithelial ovarian cancer, we analyzed alterations of the gene in 45 patients who were treated with primary cytoreductive surgery followed by 6 courses of cis‐diamminedichloroplatinum (II) (cisplatin)‐based combination chemotherapy. Homozygous deletion of p16/CDKN2 and p15/MTS2 genes was found in 8 (18%) and 15 (33%) cases, respectively. Response to the chemotherapy was confirmed by finding at second surgery after the chemotherapy in 26 patients, resulting in 17 responders and 9 nonresponders. The abundance of gene deletion in nonresponders (56%) was significantly higher (p = 0.0463) when compared to that in responders (18%). Moreover, the deletion of genes was a significant poor prognostic factor (p = 0.0441) in advanced ovarian cancer. These results suggest that deletion of p16/CDKN2 and/or p15/MTS2 is a potential indicator for poor chemotherapy response and adverse prognosis in ovarian cancer patients. © 2002 Wiley‐Liss, Inc.
Transforming growth factor‐β and Ras regulate the VEGF/VEGF‐receptor system during tumor angiogenesis
Authors: Breier Georg , Blum Sabine , Peli Janos , Groot Marcel , Wild Carola , Risau Werner , Reichmann Ernst 
Published: August 2002

AbstractThe formation of new microvasculature by capillary sprouting, or angiogenesis, is a prerequisite for solid tumor growth. The genetic alterations required to activate the angiogenic program in tumor angiogenesis are still only vaguely known, but dominantly acting oncoproteins may have a much greater impact than previously realized. Here we have studied the consequences of oncogenic transformation on tumor angiogenesis in a mouse mammary carcinoma model. We provide evidence that the expression of vascular endothelial growth factor (VEGF) and of the VEGF receptor‐2 (Flk‐1), a signaling system centrally involved in tumor angiogenesis, occurs efficiently in tumors formed by Ras‐transformed mammary epithelial cells and that both TGF‐β1 and hypoxia are potent inducers of VEGF expression in these cells. VEGF induction in the tumor periphery is mainly triggered by TGF‐β1, whereas VEGF expression in perinecrotic areas is regulated by both hypoxia and TGF‐β1. As the Ras‐transformed tumor cells convert into migrating, fibroblastoid cells that start to produce TGF‐β during tumor progression, the TGF‐β effect on VEGF expression becomes propagated throughout the tumor tissue. Thus, in progressed tumors, areas of TGF‐β1 activation and hypoxia may overlap and hence cooperate to induce VEGF expression and angiogenesis. Nevertheless, the overexpression of VEGF in non‐Ras‐transformed mouse mammary epithelial cells was not sufficient to promote vascularization in vivo. Based on these findings, we conclude that amongst the multiple mutations that render a normal cell tumorigenic, oncogenic Ras is a major player that in conjunction with the tumor's micro‐environment sets the stage for tumor cell invasion and angiogenesis. © 2002 Wiley‐Liss, Inc.
Aberrant methylation and histone deacetylation of cyclooxygenase 2 in gastric cancer
Authors: Kikuchi Takefumi , Itoh Fumio , Toyota Minoru , Suzuki Hiromu , Yamamoto Hiroyuki , Fujita Masahiro , Hosokawa Masao , Imai Kohzoh 
Published: August 2002

AbstractCyclooxygenase 2 plays a critical role in the development of gastrointestinal cancers in both human and animal models. About 80% of the gastric cancer showed a high level of expression of cyclooxygenase 2, but a subset of cases do not express without unknown reason. Aberrant methylation of CpG island of COX‐2 was examined by using a series of gastric cancer cell lines and primary gastric cancers. Two out of 8 cell lines (25%) and 11 out of 93 (12%) primary cancers showed aberrant methylation of the 5′ region of COX‐2. Methylation of COX‐2 was closely associated with loss of expression and treatment of methylation inhibitor, 5‐deoxy‐2′‐azacytidine restored the expression of COX‐2. A combined treatment of 5‐deoxy‐2′‐azacytidine and a histone deacetylese inhibitor, trichostatin A, restored re‐expression of the gene synergistically and chromatin immunoprecipitation analysis revealed that histone of methylated COX‐2 promoter is deacetylated, indicating the role of cytosine methylation and histone deacetylation in the silencing of the gene. These results indicate that a subset of gastric cancer with COX‐2 methylation evolves through the pathway that is independent of COX‐2 expression and that COX‐2 inhibitor may not be useful to induce apoptosis in these cases. © 2001 Wiley‐Liss, Inc.
A reexamination of corporate risks under shadow costs of incomplete information
Authors: Bellalah Mondher 
Published: August 2002

AbstractThe valuation of the firm and its assets has been done for a long time in the classic context of complete information. Several empirical tests of the main valuation methods reveal a divergence between theoretical prices and observed prices. These deviations might be explained by the standard assumptions of complete information. It is possible to introduce information uncertainty as done by Merton and by Bellalah in the reexamination of corporate risks in the presence of information costs. The concept of risk is useful in modelling the value of the firm and its business risk and in the definition of the required rates of return and the cost of capital of corporations. However, the main well‐known results ignore information uncertainty as defined by Merton. Using the main results from the study of Modigliani and Miller and the implications of Merton's model, we give expressions for the cost of capital and the value of the firm's equity and debt in the presence of information costs. We reexamine the relationships between interrelated risks in the same context. We introduce information costs in the computation of the cost of capital and in the pricing of equity in an option framework. When there are no information costs, the main relationships reduce to the classic results in the literature. Copyright © 2001 John Wiley & Sons, Ltd.
The Helsinki Arrangement: its impact on the provision of tied aid
Authors: Lammersen F. , Owen A.D. 
Published: August 2002

AbstractThe use of ‘tied’ loans with concessionary interest rates as an incentive for developing countries to procure capital goods from industrialized countries has been an on‐going subject of dispute amongst the latter in regard to their trade distorting impact. A major initiative by the OECD in 1992 was designed to minimize this problem, by prohibiting the use of such loans for projects that were deemed to be commercially viable. This paper assesses the impact of the change in ‘rules’ on the disbursement of concessionary loans and discusses issues that remain unresolved. Copyright © 2001 John Wiley & Sons, Ltd.
The efffects of migration and work on marriage of female garment workers in Bangladesh
Authors: Naved Ruchira T. , Newby Margaret , Amin Sajeda 
Published: August 2002

AbstractThis paper examines the effects of migration and entry into garment work on marriage for young women in Bangladesh. The data comes from a study of female garment workers and their non‐working peers conducted in
1996–97 in Bangladesh. In a country where women traditionally do not work in formal employment, and enter arranged marriages soon after puberty, the rapidly expanding garment industry offers scope for social change. The industry employs mainly young women migrating from rural areas. Previous research in Bangladesh and other countries suggests that female migrants maintain financial ties with their families in rural areas for reasons of economic and emotional security. This paper shows that many workers contribute financially to their natal families in order to maintain social networks and maximise security in marriage. Concerns regarding security lead workers to express traditional aspirations for marriage. However, weak social networks and changes in living arrangements and household structure associated with migration often dictate that migrants adopt non‐traditional and less secure marriage arrangements. Copyright © 2001 John Wiley & Sons, Ltd.