bluuebunny/crossref_metadata_2025_split huggingface dataset:
A classification of drainage and macropore flow in an agricultural catchment
Authors: Heppell C. M. , Worrall F. , Burt T. P. , Williams R. J. 
Published: August 2002

AbstractThis paper uses a variety of multivariate statistical techniques in order to improve current understanding of the antecedent and rainfall controls on drainage characteristics for an agricultural underdrained clay site. Using the dataset obtained from a two‐year hillslope study at Wytham (Oxfordshire, UK) a number of patterns in the nature and style of drainage events were explored. First, using principal components analysis, a distinction was drawn between drainflow controlled by antecedent conditions and drainflow controlled by rainfall characteristics. Dimensional analysis then distinguished between two further types of drainflow event: antecedent limited events (ALE) and non‐antecedent limited events (NALE). These were drainflow events requiring a minimum antecedent hydraulic head to occur (ALE) and events that occurred in response to rainfall irrespective of the antecedent conditions, because the rainfall was either of high enough intensity or duration to prompt a response in drainflow (NALE). 2. The dataset also made possible a preliminary investigation into the controls on and types of macropore flow at the site. Principal components analysis identified that rainfall characteristics were more important than antecedent conditions in generating high proportions of macropore flow in drainflow. Of the rainfall characteristics studied, rainfall amount and intensity were the dominant controls on the amount of macropore flow, with duration as a secondary control. Two styles of macropore flow were identified: intensity‐driven and duration‐driven. Intensity‐driven events are characterized by rainfall of high intensity and short duration. During such events the amount of macropore flow is proportional to the rainfall intensity and the interaction between macropore and matrix flow is kinetically limited. The second style of macropore flow is characterized by long‐duration events. For these events the amount of macropore flow approaches a maximum value whatever the rainfall duration. This suggests that these events are characterized by an equilibrium interaction between macropores and matrix flow. Copyright © 2002 John Wiley & Sons, Ltd.
Practical applications of spectral analysis to hydrologic time series
Authors: Fleming Sean W. , Marsh Lavenue A. , Aly Alaa H. , Adams Alison 
Published: August 2002

AbstractAn Erratum has been published for this article in Hydrological Processes 17(4) 2003, 883.
Fourier‐transform‐based spectral analysis and filtering techniques, although potentially very useful, have seen little practical application in hydrology. We provide an overview of the Fourier transform and spectral analysis and present examples of how these methods may be applied to practical hydrologic problems: determination of the frequency content of a time series; inference of the physical mechanisms responsible for this frequency content; and evaluation of the performance of a process‐based simulation model used for water resource management. In all cases, the methods performed well and were reasonably straightforward to implement, highlighting their general utility. Copyright © 2002 John Wiley & Sons, Ltd.
Significance of processes in the near‐stream zone on stream water acidity in a small acidified forested catchment
Authors: Fölster Jens 
Published: August 2002

AbstractThe near‐stream zone has received increasing attention owing to its influence on stream water chemistry in general and acidity in particular. Possible processes in this zone include cation exchange, leaching of organic matter and redox reactions of sulphur compounds. In this study the influences of processes in the near‐stream zone on the acidity in runoff from a small, acidified catchment in central southern Sweden were investigated. The study included sampling of groundwater, soil water and stream water along with hydrological measurements. An input–output budget for the catchment was established based on data from the International Co‐operative Programme on Integrated Monitoring at this site.The catchment was heavily acidified by deposition of anthropogenic sulphur, with pH in stream water between 4·4 and 4·6. There was also no relationship between stream flow and pH, which is indicative of chronic acidification. Indications of microbial reduction of sulphate were found in some places near the stream, but the near‐stream zone did not have a general impact on the sulphate concentration in discharging groundwater. The near‐stream zone was a source of dissolved organic carbon (DOC) in the stream, which had a median DOC of 6·8 mg L1. The influence on stream acidity from organic anions was overshadowed by the effect of sulphate, however, except during a spring flow episode, when additional organic matter was flushed out and the sulphate‐rich ground water was mixed with more diluted event water. Ion exchange was not an important process in the near‐stream zone of the Kindla catchment. Different functions of the near‐stream zone relating to discharge acidity are reported in the literature. In this study there was even a variation within the site. There is therefore a need for more case studies to provide a more detailed understanding of the net effects that the near‐stream zone can have on stream chemistry under different circumstances. Copyright © 2001 John Wiley & Sons, Ltd.
Prevalence of the BRCA2 6174 del T mutation in Israeli uveal melanoma patients
Authors: Iscovich Jose , Abdulrazik Mohammed , Cour Carol , Fischbein Alf , Pe'er Jacob , Goldgar David E. 
Published: August 2002

AbstractSubstantial differences exist in the incidence rates of uveal melanoma (UM) among Israeli Jewish subpopulations: high in immigrants from North America and Europe (Ashkenazic) and low in immigrants from Africa and Asia (Sepharadic). This trend persists in Israeli‐born individuals when stratified by their ancestral place of birth. There have been several anecdotal reports of uveal melanoma occurring in breast cancer families with mutations in the BRCA2 gene as well as one systematic study reporting BRCA2 mutations in UM. A single BRCA2 mutation, 6174 del T, occurs in about 1% of the Ashkenazic population and rarely in non‐Ashkenazic. To assess the contribution of this germline mutation to uveal melanoma in Jewish Israeli patients, we tested this relationship through analysis of blood samples from a series of UM patients. A total of 153 cases (84 female, 69 male) were available for study, which represents 30% of all cases of UM diagnosed in Israel during the period 1984–1999 (82% for the period 1992–1999). Of the 143 UM patients for which a result could be obtained (4 due to refusals, 6 due to damage to the blood sample), 4 (2.8%, 95% confidence interval [CI] 0–5.6) carried the 6174 del T mutation. Assuming a population frequency of the mutation of 1% as estimated among Ashkenazic Jews in the United States, the probability of observing 4 or more carriers with the 6174 del T mutation, assuming no relationship between uveal melanoma and BRCA2, is 0.057. Although our study confirms the relationship between uveal melanoma and BRCA2, it is clear that the 6174 del T mutation accounts for only a small fraction of all Israeli UM cases. Therefore, BRCA2 mutations are likely to account for an even smaller proportion in populations with low frequencies of BRCA2 alterations. © 2001 Wiley‐Liss, Inc.
Inhibition of cell proliferation, invasion, tumor growth and metastasis by an oral non‐antimicrobial tetracycline analog (COL‐3) in a metastatic prostate cancer model
Authors: Lokeshwar Bal L. , Selzer Marie G. , Zhu Bao‐Qian , Block Norman L. , Golub Lorne M. 
Published: August 2002

AbstractAntibiotic forms of tetracycline exhibit antitumor activity in some tumor models. However, their low in vivo efficacy and associated morbidity limit their long‐term application in cancer therapy. This report appraises the efficacy of doxycycline (DC) and non‐antimicrobial, chemically modified tetracyclines (CMTs) against prostate cancer. Both DC and several CMTs inhibited prostate tumor cell proliferation in vitro. Some of the CMTs were significantly more potent than DC. One of the CMTs, 6‐deoxy, 6‐demethyl, 4‐de‐dimethylamino tetracycline (CMT‐3, COL‐3), was the most potent inhibitor (50% inhibition dose [GI50] ≤ 5.0 μg/ml). Exposure of tumor cells to CMT‐3 induced both apoptosis and necrosis. Mitochondrial depolarization and increased levels of reactive hydroxyl radicals were also observed in cells treated with CMT‐3. Cell cycle arrest at the G0/G1 compartment was observed in CMT‐3‐ and DC‐treated cells. DC and CMTs also inhibited the invasive potential of the tumor cells in vitro, from 10% (CMT‐6) to >90% (CMT‐3). CMT‐3 and DC decreased matrix metalloproteinase (MMP)‐2, tissue inhibitor of MMP (TIMP)‐1 and TIMP‐2 secretion in treated cultures and inhibited activity of secreted MMPs, CMT‐3 was a stronger inhibitor. Daily oral gavage of DC and CMT‐3 inhibited tumor growth and metastasis in the Dunning MAT LyLu rat prostate tumor. Decreases in tumor growth (27–35%) and lung metastases were observed (28.9 ± 15.4 sites/animal [CMT‐3‐treated] versus 43.6 ± 18.8 sites/animal [DC‐treated] versus 59.5 ± 13.9 [control]; p < 0.01]. A delay in tumor growth (27 ± 9.3%, p < 0.05), reduction in metastases (58 ± 8%) and decrease in tumor incidences (55 ± 9%, CMT‐3‐treated) were also observed, when rats were predosed for 7 days. No significant drug‐induced morbidity was observed in any of the animals. These results, along with a recently concluded clinical trial, suggest a potential use of CMT‐3 as an oral, nontoxic drug to treat metastatic prostate and other cancers. © 2001 Wiley‐Liss, Inc.
Immunotherapy with recombinant SFV‐replicons expressing the P815A tumor antigen or IL‐12 induces tumor regression
Authors: Colmenero Paula , Chen Margaret , Castaños‐Velez Esmeralda , Liljeström Peter , Jondal Mikael 
Published: August 2002

AbstractReplicons based on alphaviruses are emerging as candidate vectors for vaccination and gene therapy purposes. We have reported previously that mice vaccinated with a recombinant Semliki Forest virus (a member of the alphavirus genus) carrying the gene encoding the P815A tumor antigen (rSFV/E‐P1A) were protected against a lethal challenge with the P815 tumor. In this study we investigated the anti‐tumor therapeutic efficacy of rSFV/E‐P1A or rSFV expressing the cytokine interleukin 12 (rSFV/IL12) on Day 5‐established tumors. The results show that both antigen‐specific and cytokine‐mediated rSFV treatments exhibited a significant effect on P815 tumor growth, by delaying tumor progression and even inducing complete tumor regressions in several mice. The therapeutic potency of these vectors was dependent on the size of the treated tumor, as treatment of mice bearing larger tumors showed lower efficacy. In addition, rSFV treatment resulted in long‐term immunity as observed by the lack of tumor recurrence in the majority of tumor‐regressing mice after rechallenge with the tumor. Furthermore, the anti‐tumor therapeutic effect was only achieved by local intratumoral injection of rSFV, as treatment by injection in the contralateral site resulted in tumor progression comparable to control‐untreated mice. Accordingly, expression of a rSFV‐RNA was localized to the tumor and draining lymph node. These results further demonstrate the potential of rSFV replicons as tumor therapeutic agents. © 2002 Wiley‐Liss, Inc.
Novel monoclonal antibody specific for the de2‐7 epidermal growth factor receptor (EGFR) that also recognizes the EGFR expressed in cells containing amplification of the EGFR gene
Authors: Johns Terrance G. , Stockert Elisabeth , Ritter Gerd , Jungbluth Achim A. , Huang H‐J. Su , Cavenee Webster K. , Smyth Fiona E. , Hall Cathrine M. , Watson Nadine , Nice Edouard C. , Gullick William J. , Old Lloyd J. , Burgess Antony W. , Scott Andrew M. 
Published: August 2002

AbstractIn some respects, the EGFR appears to be an attractive target for tumor‐targeted antibody therapy: it is overexpressed in many types of epithelial tumor and inhibition of signaling often induces an anti‐tumor effect. The use of EGFR specific antibodies, however, may be limited by uptake in organs that have high endogenous levels of the wild type EGFR such as the liver. The de2‐7 EGFR (or EGFRvIII) is a naturally occurring extracellular truncation of the EGFR found in a number of tumor types including glioma, breast, lung and prostate. Antibodies directed to this tumor specific variant of the EGFR provide an alternative targeting strategy, although the lower proportion of tumors that express the de2‐7 EGFR restricts this approach. We describe a novel monoclonal antibody (MAb 806) that potentially overcomes the difficulties associated with targeting the EGFR expressed on the surface of tumor cells. MAb 806 bound to de2‐7 EGFR transfected U87MG glioma cells (U87MG.Δ2‐7) with high affinity (∼1 × 109 M−1), but did not bind parental cells that express the wild type EGFR. Consistent with this observation, MAb 806 was unable to bind a soluble version of the wild type EGFR containing the extracellular domain. In contrast, immobilization of this extracellular domain to ELISA plates induced saturating and dose response binding of MAb 806, suggesting that MAb 806 can bind the wild type EGFR under certain conditions. MAb 806 also bound to the surface of A431 cells, which due to an amplification of the EGFR gene express large amounts of the EGFR. Interestingly, MAb 806 only recognized 10% of the total EGFR molecules expressed by A431 cells and the binding affinity was lower than that determined for the de2‐7 EGFR. MAb 806 specifically targeted U87MG.Δ2‐7 and A431 xenografts grown in nude mice with peak levels in U87MG.Δ2‐7 xenografts detected 8 h after injection. No specific targeting of parental U87MG xenografts was observed. Following binding to U87MG.Δ2‐7 cells, MAb 806 was rapidly internalized by macropinocytosis and subsequently transported to lysosomes, a process that probably contributes to the early targeting peak observed in the xenografts. Thus, MAb 806 can be used to target tumor cells containing amplification of the EGFR gene or de2‐7 EGFR but does not bind to the wild type EGFR when expressed on the cell surface. © 2002 Wiley‐Liss, Inc.
Infiltration of Th1 and Th2 lymphocytes around Hodgkin and Reed‐Sternberg (H&RS) cells in Hodgkin disease: Relation with expression of CXC and CC chemokines on H&RS cells
Authors: Ohshima Koichi , Tutiya Takeshi , Yamaguchi Takahiro , Suzuki Keiko , Suzumiya Junji , Kawasaki Chika , Haraoka Seiji , Kikuchi Masahiro 
Published: August 2002

AbstractHodgkin disease (HD) is characterized by the presence of Hodgkin and Reed‐Sternberg cells (H&RS) and a prominent lymphocytic infiltration. Various CXC and CC chemokines [e.g., interferon‐γ‐inducible protein‐10 (IP10), monokine induced by interferon‐γ (MIG) and TARC] are expressed on H&RS cells. Our study was designed to investigate the expression of MIG, IP10 and TARC on H&RS cells and their relations on lymphocyte infiltration. Immunohistochemical staining was performed using antibodies for CXCR3 (a specific receptor for IP10 and MIG), which is characteristic of Th1 helper phenotype and CCR3, CCR4 and ST2, which are features of Th2 cells. We studied 15 cases of HD [lymphocyte predominance (LP) type, 2; mixed cellularity (MC) type, 6; and nodular sclerosis (NS) type, 7]. All 6 MC cases contained TARC‐, IP10‐ and MIG‐expressing H&RS cells, however only 2 of 5 NS cases contained TARC‐expressing H&RS cells, 3 of 7 NS contained MIG‐expressing H&RS cells and only 1 of 7 NS contained IP10‐expressing H&RS cells. Neither of the 2 LP cases contained HR&S cells that expressed these chemokines. The chemokines were more frequently expressed by MC than by NS and LP types. IP10‐, MIG‐ and TARC‐positive HD cases contained higher numbers of Th2 lymphocytes (ST2‐ CCR3‐ or CCR4‐positive lymphocytes), compared to IP10‐, MIG‐ and TARC‐negative HD cases (p < 0.05 or <0.5). The number of CXCR3 (MIG and IP10 receptor)‐positive lymphocytes (Th1 lymphocytes) was not different between MIG‐ and IP10‐positive and ‐negative HD. Lymphocytes surrounding MIG‐ and IP10‐positive H&RS cells were more frequently CXCR3‐positive, however, compared to MIG‐ and IP10‐negative cases. The CCR4 (TARC receptor)‐positive lymphocytes, surrounding H&RS cells, were minority and the surrounding lymphocytes were not different between TARC‐positive and negative cases. Our results indicate that MIG, IP10 and TARC chemokines influenced the response of Th2 cells in HD. It is possible, however, that IP10 and MIG may locally influence Th1 cells via cell migration. © 2002 Wiley‐Liss, Inc.
Increased expression of CHK2 in human gastric carcinomas harboring p53 mutations
Authors: Shigeishi Hideo , Yokozaki Hiroshi , Oue Naohide , Kuniyasu Hiroki , Kondo Tomohiro , Ishikawa Takenori , Yasui Wataru 
Published: August 2002

AbstractHuman Chk1 and Chk2 are DNA damage–activated protein kinases that function as downstream mediators of ataxia‐telangiectasia mutated (ATM), which is involved in G2/M cell cycle arrest. To clarify the relation between the expression of Chk1/Chk2 and p53 gene status in human gastric carcinomas, we examined expression of Chk1, Chk2 and p53 proteins in 87 gastric carcinomas by Western blotting and immunohistochemistry. We found a significant correlation between the expression levels of Chk1 and p53 proteins in gastric carcinomas (p = 0.016). Significant statistical association was also observed between levels of Chk2 and p53 proteins (p = 0.00024). To clarify the genetic alterations of p53 in gastric carcinomas, we performed PCR‐SSCP analysis on 47 gastric carcinomas. Although we found that 5 of 7 (71%) gastric cancers expressed elevated levels of Chk1 had p53 mutation, there was not a statistically significant correlation between expression of Chk1 and genetic status of p53. We also found that 7 of 11 (78%) gastric carcinomas expressed elevated levels of Chk2 had p53 mutation, and this correlation was significant (p = 0.0157). We used a highly quantitative 5′ nuclease fluorogenic RT‐PCR method (TaqMan) to analyze the expression of Chk2 mRNA in 22 gastric carcinomas. Chk2 mRNA expression was higher in gastric carcinomas with p53 mutations compared to those harboring wild‐type p53. A significant association was recognized between the expression of Chk2 mRNA and p53 mutational status (p = 0.031). Our findings support the hypothesis that expression of Chk2 protein is increased in gastric carcinomas with mutant p53. Chk1 and Chk2 may play important roles in the checkpoint function in human gastric carcinomas harboring p53 mutation when their functions are preserved to prevent cell cycle progression. © 2002 Wiley‐Liss, Inc.
Loss of single HLA Class I allospecificities in melanoma cells due to selective genomic abbreviations
Authors: Geertsen Ralf , Böni Roland , Blasczyk Rainer , Romero Pedro , Betts David , Rimoldi Donata , Hong Xin , Laine Elisabeth , Willers Jörg , Dummer Reinhard 
Published: August 2002

AbstractExpression of human leucocyte antigen (HLA) Class I molecules is essential for the recognition of malignant melanoma (MM) cells by CD8+ T lymphocytes. A complete or partial loss of HLA Class I molecules is a potent strategy for MM cells to escape from immunosurveillance. In 2 out of 55 melanoma cell cultures we identified a complete phenotypic loss of HLA allospecificities. Both patients have been treated unsuccessfully with HLA‐A2 peptides. To identify the reasons underlying the loss of single HLA‐A allospecificities, we searched for genomic alterations at the locus for HLA Class I α‐chain on chromosome 6 in melanoma cell cultures established from 2 selected patients with MM in advanced stage. This deficiency was associated with alterations of HLA‐A2 gene sequences as determined by polymerase chain reaction‐sequence specific primers (PCR‐SSP). Karyotyping revealed a chromosomal loss in Patient 1, whereas melanoma cell cultures established from Patient 2 displayed 2 copies of chromosome 6. Loss of heterozygosity (LOH) using markers located around position 6p21 was detected in both cases. By applying group‐specific primer‐mixes spanning the 5′‐flanking region of the HLA‐A2 gene locus the relevant region was amplified by PCR and subsequent sequencing allowed alignment with the known HLA Class I reference sequences. Functional assays using HLA‐A2‐restricted cytotoxic T‐cell clones were performed in HLA‐A2 deficient MM cultures and revealed a drastically reduced susceptibility to CTL lysis in HLA‐A2 negative cells. We could document the occurrence of selective HLA‐A2 deficiencies in cultured advanced‐stage melanoma metastases and identify their molecular causes as genomic alterations within the HLA‐A gene locus. © 2002 Wiley‐Liss, Inc.
Genetic analysis of RET, GFRα1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2A
Authors: Gil Laura , Azañedo Marta , Pollán Marina , Cristobal Eva , Arribas Begoña , García‐Albert Luis , García‐Sáiz Alfredo , Maestro María Luisa , Torres Antonio , Menárguez Javier , Rojas José M. 
Published: August 2002

AbstractMultiple endocrine neoplasia type 2A (MEN 2A) is associated with specific germline missense mutations in the RET proto‐oncogene. This locus encodes a receptor tyrosine kinase whose activation requires the formation of a multimeric receptor complex including GDNF as a ligand and GFRα1 as a coreceptor. In order to explore the role of RET, GFRα1 and GDNF genes in the variation of phenotypes observed in MEN2A families, we analysed germline mutations of these genes in 4 unrelated Spanish MEN2A families (23 cases studied). We found 2 novel variants corresponding to a single change in position + 47 (intron 12) of RET and position +22 (intron 7) of GFRα1. Furthermore, we observed strong co‐segregation between 2 polymorphisms of RET [G691S (exon 11) and S904S (TCC‐TCG, exon 15) (100%, Fisher's exact test, p< 0.001)]. More interestingly, we found that these polymorphisms occurred at a significantly high frequency in patients with age at onset < 20 years old (Kruskal‐Wallis's and Fisher's exact test, p = 0.007). These findings suggest that the G691S and S904S variants of RET may somehow play a role on the age of onset of MEN 2A. © 2002 Wiley‐Liss, Inc.