bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical trial of deferiprone iron chelation therapy in β‐thalassaemia/haemoglobin E patients in Thailand
Authors: Pootrakul Pensri , Sirankapracha Pornpan , Sankote Jongkal , Kachintorn Udom , Maungsub Wanna , Sriphen Kosit , Thakernpol Kleonphan , Atisuk Kanit , Fucharoen Suthat , Chantraluksri Udom , Shalev Oded , Hoffbrand A. Victor
Published: July 2003

Summary. Nine patients with either β‐thalassaemia/haemoglobin E (7) or homozygous β‐thalassaemia (2) not requiring regular transfusions were treated with the oral iron chelator, deferiprone 25–50 mg/kg/d for between 17 and 86 weeks (mean 49 weeks). There were significant decreases in serum ferritin (initial mean ± standard deviation 2168 ± 1142, final 418 ± 247 µg/l; t‐test for paired samples, P = 0·005), hepatic iron (initial 20·3 ± 6·26, final 11·7 ± 4·83 mg/g/dry weight; P = < 0·02), red cell membrane iron (initial 76·2 ± 3·64, final 7·2 ± 0·56 mmol/mg protein; P = < 0·0005) and serum non‐transferrin bound iron (initial 9·0 ± 0·56, final 5·9 ± 0·89 µmol/l; P = < 0·0005). There was also a significant rise in serum erythropoietin (initial 240 ± 195·1, final 433·2 ± 269·2 U/l; P = 0·034). The haemoglobin level rose in three patients and transfusion requirements were reduced substantially in four patients. Serum thiobarbituric acid reactive substance (TBARS) also fell in six of eight patients. Patients generally improved clinically, with weight gain observed. Side‐effects were mild and included gastrointestinal symptoms (6) and arthralgia (1), not requiring withdrawal of the drug. One patient died at 17 weeks of therapy as a result of an intercurrent infection. His neutrophil count was normal. We conclude that deferiprone is an effective, well‐tolerated iron chelator for patients with thalassaemia intermedia. Further studies are needed to determine the optimum dose and length of treatment needed to reduce iron burden to a safe level in these patients.
Value of comparative genomic hybridization and fluorescence in situ hybridization for molecular diagnostics in multiple myeloma
Authors: Liebisch Peter , Viardot Andreas , Baßermann Nicole , Wendl Christiane , Roth Katrin , Goldschmidt Hartmut , Einsele Hermann , Straka Christian , Stilgenbauer Stephan , Döhner Hartmut , Bentz Martin
Published: July 2003

Summary. Chromosomal abnormalities, such as 13q deletions, are emerging as important prognostic factors in multiple myeloma. Fluorescence in situ hybridization (FISH) using specific DNA probes is the technique most widely used for the determination of genomic aberrations in this disease. The utility of comparative genomic hybridization (CGH) for molecular diagnostics in plasma cell malignancies has not been systematically analysed. We investigated tumour samples of patients with multiple myeloma (n = 43) or plasma cell leukaemia (n = 3) using CGH and FISH with five DNA probes localized to chromosome bands 1p22, 6q21, 11q22–q23, 13q14 and 17p13. By CGH, the most frequent genomic changes were gains on chromosomes 1q, 9q and 11q, as well as losses on chromosomes 13q, 6q, Xp and Xq. By FISH, trisomy 11q was identified at a similar frequency to the 13q deletion (42%). Compared with FISH data, the sensitivity of CGH was 80·7% and the specificity was 97·5%. Thirty‐two aberrations found by FISH were not identified by CGH, mostly as a result of the proportion of cells carrying the respective aberrations, or because of the limited spatial resolution of CGH. Our data indicate that, for clinical molecular diagnostics in multiple myeloma, FISH with a disease‐specific DNA probe set is superior to CGH analysis.
Treatment stratification based on initial in vivo response in acute myeloid leukaemia in children without Down's syndrome: results of NOPHO‐AML trials
Authors: Lie Sverre O. , Abrahamsson Jonas , Clausen Niels , Forestier Erik , Hasle Henrik , Hovi Liisa , Jonmundsson Gudmundur , Mellander Lotta , Gustafsson Göran
Published: July 2003

Summary. Three consecutive protocols for childhood acute myeloid leukaemia (AML) have been used in the Nordic countries since 1984: the Nordic Society for Paediatric Haematology and Oncology (NOPHO)‐AML84 was of moderate intensity, NOPHO‐AML88 of high intensity with upfront loading and aggressive consolidation. NOPHO‐AML93 utilized the same treatment blocks as NOPHO‐AML88, but after the first block those children with a hypoplastic non‐leukaemic bone marrow were allowed to recover from aplasia. Poor responders received intensified induction therapy. Between January 1993 and December 2000, 219 children without Down's syndrome were entered on NOPHO‐AML93. Compared with NOPHO‐AML88, the event‐free survival (EFS) at 7 years increased from 41% to 49% (P = 0·06) and 7‐year overall survival increased from 47% to 64% (P < 0·01). Toxic death during induction was reduced from 10% to 3%. Survival was similar in patients receiving stem cell transplantation or chemotherapy only in first remission. The major prognostic factors in NOPHO‐AML93 were response to therapy and cytogenetics. A total of 67% of patients achieved remission after the first induction course and showed an EFS of 56% compared with 35% in those not in remission (P < 0·01). Cytogenetic results were obtained in 95% of patients. Patients with t(9;11) (p22;q23) (n = 16) experienced a significantly better EFS (86%) than other cytogenetic groups. The overall outcome was improved by employing the previous toxic protocol with different timings, and through individualizing therapy according to the initial response of the patient.
The Rh complex exports ammonium from human red blood cells
Authors: Hemker Mirte B. , Cheroutre Goedele , Van Zwieten Rob , Maaskant‐van Wijk Petra A. , Roos Dirk , Loos Johannes A. , Van Der Schoot C. Ellen , Von Dem Borne Albert E. G. Kr.
Published: July 2003

Summary. The Rh blood group system represents a major immunodominant protein complex on red blood cells (RBC). Recently, the Rh homologues RhAG and RhCG were shown to promote ammonium ion transport in yeast. In this study, we showed that also in RBC the human Rh complex functions as an exporter of ammonium ions. We measured ammonium import during the incubation of RBC in a solution containing a radiolabelled analogue of NH4Cl (14C‐methyl‐NH3Cl). Rhnull cells of the regulator type (expressing no Rh complex proteins) accumulated significantly higher levels (P = 0·05) of radiolabelled methyl‐ammonium ions than normal RBC, at room temperature. Rhnull cells of the amorph type (expressing limited amounts of Rh complex proteins) accumulated an intermediate amount of methyl‐ammonium ions. To show that decreased ammonium export contributes to its accumulation, the release of intracellular methyl‐ammonium from the cells was measured over time. In 30 s, normal RBC released 87% of the intracellular methyl‐ammonium ions, whereas Rhnull cells of the regulator type released only 46%. We conclude that the Rh complex is involved in the export of ammonium from RBC.
Expression and structural analysis of glucocorticoid receptor isoform gamma in human leukaemia cells using an isoform‐specific real‐time polymerase chain reaction approach
Authors: Beger Carmela , Gerdes Katrin , Lauten Melchior , Tissing Wim J. E. , Fernandez‐Munoz Ivonne , Schrappe Martin , Welte Karl
Published: July 2003

Summary. Glucocorticoids are broadly used for chemotherapy in childhood acute lymphoblastic leukaemia (ALL). The intracellular effects of glucocorticoids are mediated through the glucocorticoid receptor. The human glucocorticoid receptor gamma isoform (hGR‐gamma) differs from the main isoform (hGR‐alpha) by an additional amino acid within the DNA binding domain of the receptor protein. This may decrease hGR‐alpha‐mediated transcriptional activation. The importance of hGR‐gamma expression in childhood ALL is unknown. To evaluate hGR‐gamma mRNA expression levels, a real‐time polymerase chain reaction (PCR)‐based approach, allowing the selective amplification of hGR‐gamma, was developed and optimized. We were able to demonstrate target selectivity of hGR‐gamma amplification using sequence‐specific primers. Studying the structure of the 3′ end of hGR‐gamma, a combination of this isoform with other hGR isoforms could be demonstrated. Using analysis of hGR‐gamma‐specific amplification in comparison with the expression of hGR‐total (all isoforms) in leukaemic blasts from patients with either a good response to prednisone (PGR) or poor‐prednisone response (PPR) in vivo, relative hGR‐gamma expression was observed to be lower in cells from patients with PGR compared with PPR, in particular after 10 h of dexamethasone stimulation. These data were correlated with cell survival, demonstrating a more pronounced induction of apoptosis in cells from patients with PGR as compared with PPR.
Bone marrow angiogenesis and circulating plasma cells in multiple myeloma
Authors: Kumar Shaji , Witzig Thomas E. , Greipp Philip R. , Rajkumar S. Vincent
Published: July 2003

Summary. Bone marrow (BM) angiogenesis is increased in multiple myeloma (MM) and has prognostic significance. The presence of circulating plasma cells (PCs) in MM is associated with a poorer prognosis. We examined BM biopsies obtained at diagnosis of MM for angiogenesis, and correlated the microvessel density (MVD) with the presence of circulating PCs. There was a positive correlation between the absolute number of circulating PCs and the mean MVD. This relationship was independent of the disease activity and of the PC burden in the marrow. The increased angiogenesis may promote plasma cell proliferation and enable PC migration into the circulation.
Vα24+ natural killer T‐cell responses against T‐acute lymphoblastic leukaemia cells: implications for immunotherapy
Authors: Takahashi Tsuyoshi , Haraguchi Kyoko , Chiba Shigeru , Yasukawa Masaki , Shibata Yoichi , Hirai Hisamaru
Published: July 2003

Summary. Human Vα24+ natural killer T (NKT) cells correspond to mouse Vα14+ NKT cells, both cell types use an invariant T‐cell receptor‐α chain and are activated by glycolipids in a CD1d‐dependent manner. Mouse Vα14+ NKT cells have been reported to have an antitumour effect in vivo. Human Vα24+ NKT cells can kill a proportion of tumour cells in a CD1d‐dependent manner in vitro. We report here that many human leukaemic T‐cell lines express CD1d and can be directly killed by Vα24+ NKT cells. This killing activity was enhanced in the presence of α‐galactosylceramide (α‐GalCer), a ligand of Vα24+ NKT cells. Moreover, primary leukaemic T cells from five of eight T‐cell acute lymphoblastic leukaemia (T‐ALL) patients expressed CD1d and were good targets of Vα24+ NKT cells. This cytotoxicity was increased in the presence of α‐GalCer. Our results suggest that T‐ALL is a good candidate for Vα24+ NKT‐cell‐based immuno‐cell therapy.
CYP3A genotypes and treatment response in paediatric acute lymphoblastic leukaemia
Authors: Aplenc Richard , Glatfelter Wendy , Han Peggy , Rappaport Eric , La Mei , Cnaan Avital , Blackwood M. Anne , Lange Beverly , Rebbeck Timothy
Published: July 2003

Summary. Acute lymphoblastic leukaemia (ALL) is the most common paediatric cancer with a cure rate of approximately 80%. Relapse occurs despite treatment stratification based on clinical criteria. Relapse risk in ALL may be related to simple nucleotide polymorphisms (SNPs) of enzymes that metabolize chemotherapeutic agents. We evaluated whether SNPs in the cytochrome P450 3A family (CYP3A4*1B, CYP3A5*3 and CYP3A5*6) were associated with relapse risk on a national Children's Cancer Group (CCG) paediatric ALL trial (CCG‐1891). CCG‐1891 enrolled 1204 patients, and obtained both relapse and toxicity data prospectively. One hundred and twenty‐four relapsed patients and 409 non‐relapsed patients were assayed for each SNP. CYP3A variants were not associated with an increased risk of relapse. However, patients with the CYP3A4*1B and CYP3A5*3 genotypes had a decreased risk of peripheral neuropathy that was statistically significant on univariate analysis. After correction for multiple comparisons, the association between CYP3A*1B and CYP3A5*3 genotypes approached, but did not reach, statistical significance. CYP3 genotypes may not significantly modify the risk of relapse in childhood ALL, but may modify the risk of toxicity.
Rapid, accurate genotyping of β‐thalassaemia mutations using a novel multiplex primer extension/denaturing high‐performance liquid chromatography assay
Authors: Wu Grant , Hua Liang , Zhu Jim , Mo Qiu‐Hua , Xu Xiang‐Min
Published: July 2003

Summary. β‐thalassaemia is a common inherited disorder of haemoglobin synthesis worldwide, with an estimated 3–10% frequency in certain regions. Rapid, accurate genotyping methodologies for specific, causative mutations of the β‐globin gene are needed for pre‐ and postnatal screening and diagnosis of this disease in different ethnic populations. In this study, we performed a novel multiplex primer extension (PE) reaction in combination with denaturing high‐performance liquid chromatography (DHPLC) for simultaneously detecting and genotyping the five most common molecular lesions in the β‐globin gene [codons (CDs) 41–42 (–TCTT), IVS‐2‐654 (C→T), − 28 (A→G), CD17 (A→T) and CD71–72 (+ A)] in Chinese populations. This method involved the amplification of β‐globin target sequence followed by a purification step, a multiplex PE reaction that did not require labelled oligonucleotides, and a fully‐denaturing DHPLC analysis on the Transgenomic Wave DNA fragment analysis system. In a blinded study, this technique accurately genotyped 100% (120/120) of samples previously characterized by reverse‐dot blot and direct sequencing, and was used successfully for prenatal diagnosis of β‐globin mutations in six Chinese families. This study validated the combined PE/DHPLC approach as simple, rapid, highly accurate and cost‐effective for use in genotyping common disease‐causing mutations, including substitutions, insertions and deletions in β‐thalassaemia, and strongly suggests that this technique can be used successfully in other genetic diseases.
β7E–β132K salt bridge and sickle haemoglobin stability and conformation
Authors: Fablet Christophe , Chen Qiuying , Baudin‐Creuza Véronique , Marden Michael C. , Nagel Ronald L. , Pagnier Josée , Hirsch Rhoda Elison
Published: July 2003

Summary. The liganded (R‐state) form of sickle cell haemoglobin (HbS) is of particular relevance at non‐polymerizing concentrations as oxy HbS exhibits unusual properties compared with oxy HbA: mechanical precipitability (resulting from surface denaturation), greater unfolding at an air–water interface and a tendency to oxidize more readily. In human haemoglobins, the β7 (A4) Glu residue forms an intrachain salt bridge with β132 (H10) Lys in both liganded and deoxy structures. In the present study, recombinant haemoglobins with substitutions in the β7 and β132 sites were studied in order to determine the role of the β7–β132 salt bridge on Hb conformational integrity and stability. The elimination of this interhelix bridge correlates with enhanced surface denaturation and conformational alterations in the central cavity 2,3‐diphosphoglycerate (DPG) cleft and α1β2 interface. The A‐helix β7 Ala substitution generates a class of conformational change at the DPG pocket and α1β2 interface that is distinct from that dictated by the H‐helix β132 Ala substitution. These results are significant with regard to the communication pathway between the α1β1 and α1β2 interfaces, and the new understanding of Hb allostery dependent upon tertiary structural constraints caused by effector binding to the R‐state.
Progression of myelodysplastic syndrome: allelic loss on chromosomal arm 1p
Authors: Mori Naoki , Morosetti Roberta , Mizoguchi Hideaki , Koeffler H. Phillip
Published: July 2003

Summary. Myelodysplastic syndrome (MDS) is a common neoplasm of haematopoietic pluripotent stem cells. Although one third of MDS patients evolve to acute myeloid leukaemia (AML), little is understood about the mechanisms responsible for this progression. We have previously detected the frequent loss of heterozygosity (LOH) on the short arm of chromosome 1 in blast crisis of chronic myelocytic leukaemia. In this study, we examined the chromosomal arm 1p for allelic loss in the progression of MDS to AML, using 17 microsatellite markers spanning chromosome 1 in 20 patients who progressed from MDS to AML. DNA was extracted from slides of bone marrow smears. In each patient, DNA from MDS was analysed alongside DNA from AML. Allelic loss on 1p was observed in six of the 20 individuals (30%). Serial cytogenetic information was available in five of the six patients with LOH on 1p; no deletions in this region were detected. Three samples showed LOH at all informative loci on 1p. The other three samples showed LOH on at least one but not all loci on 1p with consensus regions of LOH located distal to D1S253 (1p36.3) and probably proximal to D1S496 (1p32−). Our results suggest that tumour suppressor genes that play an important role in the progression of MDS to AML may reside in at least two different regions on 1p.
Efficacy of a single, weekly dose of recombinant erythropoietin in myelodysplastic syndromes
Authors: Musto Pellegrino , Falcone Antonietta , Sanpaolo Grazia , Bodenizza Carlo , La Sala Antonio , Perla Gianni , Carella Angelo Michele
Published: July 2003

Summary. Thirteen patients with low‐to‐intermediate risk myelodysplastic syndrome (MDS) received recombinant erythropoietin (r‐EPO) at the single, weekly dose of 40·000 U for at least 8 weeks. Five patients (38·4%) achieved a major erythroid response (increased haemoglobin levels > 2 g/dl and/or transfusion independence), which is currently maintained after 3–11 months, without modification of r‐EPO dose. This study suggests that 40·000 U r‐EPO given once a week may be at least as effective as the more frequent (daily or three times a week) administrations of the drug usually employed in MDS patients.
Haptoglobin type neither influences iron accumulation in normal subjects nor predicts clinical presentation in HFE C282Y haemochromatosis: phenotype and genotype analysis
Authors: Carter Kymberley , Bowen Derrick J. , McCune C. Anne , Worwood Mark
Published: July 2003

Summary. In the UK, 90% of patients with hereditary haemochromatosis (HH) are homozygous for HFE C282Y, as are one in 150 people in the general population. However, only a minority of these will develop clinical haemochromatosis. Iron loss modifies iron accumulation but so may other genetic factors. Haptoglobin (Hp) exists as three major types (Hp 1‐1, Hp 2‐1 or Hp 2‐2) and binds free plasma haemoglobin. In men, Hp 2‐2 has been shown to be associated with increased macrophage iron accumulation and serum ferritin concentration. Furthermore, the frequency of Hp 2‐2 was shown to be increased in patients with HH. We determined Hp types by phenotyping and genotyping 265 blood donor control subjects and 173 subjects who were homozygous for HFE C282Y. The latter group included 66 blood donors lacking clinical features suggestive of haemochromatosis and without a known family history, and 68 patients presenting clinically with haemochromatosis. Hp 2‐2 frequencies did not differ in control subjects and C282Y homozygotes. Hp 2‐2 was not a risk factor for disease development in HH. To investigate the relationship between iron accumulation and haptoglobin type, we determined transferrin saturation and serum ferritin concentration in 192 male, first‐time blood donors aged 20–40 years who lacked both HFE C282Y and H63D. Transferrin saturation and serum ferritin concentrations did not vary with Hp type.
How myeloma cells escape bisphosphonate‐mediated killing: development of specific resistance with preserved sensitivity to conventional chemotherapeutics
Authors: Salomo Morten , Jurlander Jesper , Nielsen Lars Bo , Gimsing Peter
Published: July 2003

Summary. Although amino‐bisphosphonates (N‐BPs) induce apoptosis of myeloma cells in vitro, most in‐vivo studies fail to demonstrate a corresponding antitumour effect. This discrepancy might reflect the development of resistance to the antitumour effects of N‐BP in myeloma cells when they are exposed to N‐BP for a prolonged time. To test this hypothesis, two N‐BP‐sensitive human myeloma cell lines were continuously exposed to increasing concentrations of the N‐BP alendronate for 6 weeks. During this treatment period, 10 out of 10 sublines developed reduced apoptotic and antiproliferative responses to alendronate treatment. This de novo alendronate resistance was accompanied by resistance to another N‐BP (zoledronate) but not to an inhibitor of 3‐hydroxy‐3‐methylglutaryl CoA reductase or Fas ligand. Importantly, N‐BP‐resistant myeloma cells also remained sensitive to conventional myeloma chemotherapeutics (melphalan, doxorubicin and vincristine). Further analysis of the N‐BP‐resistant cells revealed an increased activity of the N‐BP‐specific target enzyme farnesyl pyrophosphate synthase, without upregulation of its gene transcription. Our results suggest that continuous exposure of myeloma cells to alendronate leads to the development of N‐BP resistance. This is associated with an increased activity of farnesyl pyrophosphate synthase and does not evolve from defective apoptotic pathways. Importantly, the antitumour effects of conventional myeloma chemotherapeutics are preserved in the N‐BP‐resistant myeloma cells.
Inhibition of the proteasome induces cell cycle arrest and apoptosis in mantle cell lymphoma cells
Authors: Bogner Christian , Ringshausen Ingo , Schneller Folker , Fend Falko , Quintanilla‐Martinez Leticia , Häcker Georg , Goetze Katharina , Oostendorp Robert , Peschel Christian , Decker Thomas
Published: July 2003

Summary. Mantle cell lymphoma (MCL) is a distinctive non‐Hodgkin's lymphoma subtype, characterized by overexpression of cyclin D1 as a consequence of the chromosomal translocation t(11;14)(q13;q32). MCL remains an incurable disease, combining the unfavourable clinical features of aggressive and indolent lymphomas. The blastic variant of MCL, which is often associated with additional cytogenetic alterations, has an even worse prognosis and new treatment options are clearly needed. The present study investigated the effect of a specific proteasome inhibitor, lactacystin, on cell cycle progression and apoptosis in two lymphoma cell lines harbouring the t(11;14)(q13;q32) and additional cytogenetic alterations, including p53 mutation (NCEB) and p16 deletion (Granta 519). Granta cells were more susceptible to inhibition of the proteasome with respect to inhibition of proliferation and apoptosis induction. No changes were observed in the expression levels of the G1 regulatory molecules cyclin D1 and cdk4, but cell cycle arrest and apoptosis induction was accompanied by accumulation of the cdk inhibitor p21 in both cell lines. Increased p53 expression was only observed in Granta cells with wild‐type p53. Cleavage of procaspase‐3 and ‐9 was observed but cleavage of procaspase‐8 was not involved in apoptosis induction. The proapoptotic effect of lactacystin was reversed by pretreatment with the pancaspase inhibitor zVAD.fmk. Lactacystin was also effective in inducing apoptosis in lymphoma cells from MCL patients. We conclude that inhibition of the proteasome might be a promising therapeutic approach for this incurable disease.
Effect of harvest date on the chemical composition and nutritive value of Cerastium holosteoides
Authors: Kramberger B. , Klemenčič S.
Published: July 2003

Abstract Cerastium holosteoides is a short‐lived plant often found in small proportions on dry and mesotropic semi‐natural, species‐rich grassland communities. To obtain more information about its nutritive value, two experiments on Arrhenatheretum elatioris grassland were carried out to examine the effect of harvest date on in vitro organic matter digestibility (IVOMD), neutral‐detergent fibre (NDF), acid‐detergent fibre (ADF), acid‐detergent lignin (ADL), estimated net energy for lactation (NEL) and crude protein (CP) concentrations of C. holosteoides, and selection of this plant by dairy cows grazing on semi‐natural grassland. C. holosteoides starts flowering in spring and continuously develops new flowers on new branches throughout the summer. Harvests were made in relation to particular growth stages of Dactylis glomerata present in the sward: (A) tillering; (B) stem elongation; (C) ear emergence; (D) flowering; and (E) ripening.

Chemical composition and nutritive value were evaluated in 1998 and 1999. With advancing maturity, IVOMD of C. holosteoides decreased from 0·771 at growth stage A to 0·485 at growth stage E. At the same time, CP concentration decreased from 153 to 69 g kg−1 dry matter (DM) and estimated NEL concentration from 6·00 to 4·07 MJ kg−1 DM. With advancing maturity, there was a significant increase in NDF, ADF and ADL concentrations. In the summer harvest season, C. holosteoides contained significantly higher NDF, ADF and ADL concentrations, lower NEL concentration and had a lower IVOMD value than in the spring. Differences between years were also found for IVOMD and for NDF, ADF, ADL and NEL concentrations.

In a grazing experiment in the year 1999, at growth stage B, Simmental cows grazed an A. elatioris sward in which the main species was D. glomerata (0·092), and the proportion of C. holosteoides was 0·034. C. holosteoides was, on average, grazed by cows to the same relative extent as other species in the sward.
The effect of concentrate feed level on the response of lactating dairy cows to a constant proportion of fodder beet inclusion in a grass silage‐based diet
Authors: Ferris C. P. , Patterson D. C. , Gordon F. J. , Kilpatrick D. J.
Published: July 2003

Abstract The effects of level of concentrate supplementation on the response of dairy cows to grass silage‐based diets containing a constant proportion of fodder beet were examined. Forty Holstein‐Friesian dairy cows of mixed parity were used in a 2 × 5 factorial design experiment. Two basal diet types [grass silage alone or grass silage mixed with fodder beet in a 70:30 dry matter (DM) ratio] were offered ad libitum, and the effects of five levels of concentrate supplementation (mean = 3·0, 5·3, 7·5, 9·8 and 12·0 kg DM per cow d−1) were examined. Concentrate supplements were offered via an out‐of‐parlour feeding system. These treatments were examined in a three‐period (period length = 4 weeks) partially balanced changeover design experiment.

Fodder beet inclusion had no significant effect on the estimated metabolizable energy (ME) concentration of the ration (P > 0·001). Total DM intake, estimated ME intake, milk yield, milk protein content and milk energy output all showed significant linear increases with increasing level of concentrate inclusion (P < 0·001) while, in addition, milk yield and milk energy output exhibited a significant quadratic increase (P < 0·01). The inclusion of fodder beet in the diet reduced silage DM intake (P < 0·01) but resulted in an increase in total DM intake and estimated ME intake (P < 0·001). However, inclusion of fodder beet had no significant effect on milk yield (P > 0·05), while increasing milk protein content and milk energy output (P ≤ 0·05). Milk energy output, as a proportion of estimated ME intake, was significantly (P < 0·001) reduced by fodder beet inclusion (0·44 vs. 0·38).

Despite large increases in estimated ME intake with the inclusion of fodder beet at all levels of concentrate supplementation, milk energy output responses were small, resulting in an overall reduction in the efficiency of conversion of ME intake into milk energy output. An increased partitioning of dietary ME intake to tissue gain is suggested as the most likely explanation for the observations made.
Intercropped wheat (Triticum aestivum L.) and bean (Vicia faba L.) as a whole‐crop forage: effect of harvest time on forage yield and quality
Authors: Ghanbari‐Bonjar A. , Lee H. C.
Published: July 2003

Abstract Sole crops and intercrops of wheat (Triticum aestivum L.) and bean (Vicia faba L.), at three harvest dates, representing successive growth stages, were evaluated for biomass production of whole‐crop forage and quality characteristics of crude protein (CP), neutral‐detergent fibre (NDF), acid‐detergent fibre (ADF), water‐soluble carbohydrate (WSC) concentrations and ash content. These tests were carried out for two field experiments, respectively, drilled during the spring of 1997 and autumn of 1997 on Imperial College Farm, Wye, UK. Results indicated that optimum forage yield and quality were obtained from the second to third harvest dates for the spring‐drilled experiment and the second harvest for the autumn‐drilled experiment. Wheat and bean intercrops were higher in total forage dry matter (DM) yield than either wheat or bean grown as sole crops. Field bean intercropped with wheat led to increased forage quality (CP and NDF concentrations) compared with sole wheat, and higher WSC concentrations compared with sole bean. Intercrops also enhanced weed suppression compared with sole bean. It is suggested that winter wheat–bean intercrops may have considerable potential as a moderate‐yielding, relatively high‐quality, low‐input and environmentally benign forage crop with considerable potential with regard to yield and quality and warrant further study.
Performance of white clover varieties combined in blends and alone when grown with perennial ryegrass under sheep and cattle grazing
Authors: Williams T. A. , Abberton M. T. , Rhodes I.
Published: July 2003

Abstract Two experiments were carried out to evaluate the performance of blends of three white clover (Trifolium repens L.) varieties in comparison with the component varieties and three other varieties sown individually in a mixture with perennial ryegrass (Lolium perenne L.). The plots were grazed rotationally in Experiment 1 by cattle and sheep and in Experiment 2 by sheep alone. In both experiments, the blend was composed of three medium‐leaved varieties (AberDai, AberVantage and AberHerald), but with different relative contributions of the three varieties in the two experiments. Dry matter (DM) yields of white clover and perennial ryegrass were assessed in replicate plots for two years (1999 and 2000) after the establishment year. In Experiment 1, there was no significant difference between the DM yields of white clover or perennial ryegrass in either year. The decline in DM yield of white clover between years that was observed for some varieties was not found for the blend. In Experiment 2, significant differences were found in DM yields of white clover in both years. In 1999, AberDai had the highest DM yield. In 2000, AberHerald and AberVantage had the highest DM yields, and AberDai showed a decline in DM yield that was mirrored by the mean for all the white clover varieties. In both experiments, the blend did not show significantly higher DM yield than one or more of its components; indeed, in Experiment 2, it was significantly lower yielding than AberDai in 1999. However, where one component of the blend declined in DM yield between years, this was compensated for by an increase in the yield of another component. These preliminary findings suggest that the yield stability of blends may give them a potential role in agricultural practice.
Changes in species composition of abandoned sown swards after imposing seasonal cutting treatments
Authors: Marriott C. A. , Bolton G. R. , Fisher J. M.
Published: July 2003

Abstract Seasonal cutting treatments were imposed on abandoned perennial ryegrass/white clover swards at three sites in the UK to determine the impact on species diversity and the contribution of different species to biomass. Before the cutting experiment, the abandoned swards had received no fertilizer applications and had been neither grazed nor cut for 3 years. The original sown species, Lolium perenne and Trifolium repens, had virtually disappeared during this period. Self‐sown grasses, including Agrostis capillaris, Dactylis glomerata, Festuca rubra, Holcus mollis, Poa pratensis and P. trivialis, had become dominant at two sites. Ranunculus repens was the dominant species at the third site, and self‐sown grasses, such as Holcus lanatus and P. trivialis, and Juncus and Carex species were also present. The standing herbage in 2·5 m × 2·5 m subplots was cut to 2·5 cm above ground level and removed annually in either June or October for 7 years at two sites and 6 years at the third site. Total biomass removed was generally < 4 t dry matter (DM) ha−1, and both total and live biomass decreased over time in the June cutting treatment at two sites. There were large changes in species composition after initiating the two cutting treatments. The numbers of grass and dicot species increased, although many new species had a low frequency of occurrence. The contribution of species to biomass changed over time, with species showing a vegetative regenerative strategy decreasing over time at one site. At this site, annual cutting in June was slightly more effective than cutting in October in reducing the dominance of R. repens; cutting in early October effectively reduced Juncus spp. At two sites, there was a decrease in the contribution of the species group showing seasonal regeneration by seed, and differences between cutting dates for two species within this group at one site. L. perenne and T. repens remained at much lower levels than in adjacent unfertilized, grazed swards. Reseeding may be necessary to create species assemblages for ecological and agricultural objectives.
The effects of high‐concentrate diets and pasture on the concentration of conjugated linoleic acid in beef muscle and subcutaneous fat
Authors: Steen R. W. J. , Porter M. G.
Published: July 2003

Abstract In view of the evidence indicating several potential benefits of high intakes of conjugated linoleic acid (CLA) on human health, an experiment was conducted to examine the effects of the diet of beef cattle on the total CLA concentration in muscle and subcutaneous fat. High‐concentrate [steers consumed 515 g concentrates and 485 g grass silage kg−1 dry matter (DM) for 8 weeks followed by 887 g concentrates and 113 g grass silage kg−1 DM for 14 weeks until slaughter] and high‐forage (steers consumed 803 g grass silage and 197 g concentrates kg−1 for 8 weeks followed by grass silage only for 10 weeks and then grazed perennial ryegrass‐based pasture for 23 weeks until slaughter) treatments were imposed on 48 steers, which were crosses of continental beef breeds (initially 414 kg live weight) The concentrates were based on barley, extracted soyabean meal, molassed sugarbeet pulp and maize meal. The silages were of medium to low digestibility and contained 117–137 g crude protein kg−1 DM and 83–158 g ammonia‐N kg−1 total N. The pasture was of high quality and contained 168 g crude protein, 234 g acid‐detergent fibre and 222 g water‐soluble carbohydrate kg−1 DM. Samples of muscle were taken post slaughter from the m. semimembranosus, m. gluteobiceps, m. longissimus and m. deltoideous muscles, and subcutaneous fat was taken from over the m. longissimus. Concentrations of total CLA in the tissues were for the high‐concentrate and high‐forage treatments, respectively (mg 100 g−1 fresh tissue), m. gluteobiceps 18 and 47 (s.e. 3·5); m. semimembranosus 9 and 20 (s.e. 1·6); m. longissimus 15 and 35 (s.e. 3·2), m. deltoideous 20 and 59 (s.e. 4·3); subcutaneous fat 584 and 1975 (s.e. 138·7). It is concluded that muscle and subcutaneous fat tissue from grass‐fed cattle contained three times as much CLA as those from concentrate‐fed cattle, and that the consumption of beef from grass‐fed cattle should be effective in increasing the intake of CLA by humans.
Fungal endophytes in grasses from semi‐arid permanent grasslands of western Spain
Authors: Zabalgogeazcoa I. , De Aldana B. R. Vázquez , Ciudad A. García , Criado B. García
Published: July 2003

Abstract A survey of grass species associated with Epichloë and Neotyphodium fungal endophytes was made in permanent semi‐arid grasslands of western Spain. Endophytes were isolated from 11 of 49 grass species analysed. Infected plants of Festuca arundinacea, Festuca rubra, Dactylis glomerata and Lolium perenne were detected at most locations studied. The grasses, Agrostis castellana, Brachypodium phoenicoides and Festuca ampla, are previously unknown endophyte hosts. The results obtained show that endophyte–grass interactions are present in the grasslands where this study was conducted.
Incidence of microdochium patch disease in golf putting greens and a relationship with arbuscular mycorrhizal fungi
Authors: Gange A. C. , Case S. J.
Published: July 2003

Abstract A survey of pesticide records of golf courses was conducted to ascertain the incidence of microdochium patch disease, the most important turf grass pathogen in the UK. Disease incidence has remained steady over the last 10 years, but a wide variation was found in the incidence between courses. On average, golf courses suffered more than seven separate attacks of the disease per annum, with two distinct patterns being found. In one, disease was confined to spring and autumn, while in the other, outbreaks occurred with a similar frequency throughout the year. A negative correlation was found to exist between arbuscular mycorrhizal (AM) fungal abundance and disease incidence, while addition of AM fungi to a putting green produced some evidence that this resulted in a reduction in pathogen attack. It is concluded that AM fungi may have potential for use in a biocontrol programme against microdochium patch in fine turf.
Dry matter production of white clover (Trifolium repens L.), Caucasian clover (T. ambiguum M. Bieb.) and their associated hybrids when grown with a grass companion over 3 harvest years
Authors: Marshall A. H. , Williams A. , Abberton M. T. , Michaelson‐Yeates T. P. T. , Powell H. G.
Published: July 2003

Abstract The dry matter (DM) production of Trifolium repens, T. ambiguum and the backcross 1 (BC1) and backcross 2 (BC2) hybrids with T. repens as the recurrent parent were compared in mixtures with an intermediate heading variety of perennial ryegrass (Lolium perenne L.) under a cutting‐only management over 3 harvest years. Plots of parental legume species and backcross hybrids were established from small plantlets and oversown with the companion grass. In the first harvest year, the DM yield of clover in T. repens plots was greater than that in the BC2 plots and both greater than in the BC1 plots, whilst in the second and third harvest years differences between the DM yield of clover in the T. repens and the BC1 and BC2 hybrid plots were small. Similar results were obtained for the DM yield of total herbage. There were also differences in seasonal growth in the first harvest year, when yield of clover in T. repens plots was greater than in the BC1 and BC2 hybrid plots at early cuts but not at later cuts. Few differences in seasonal growth were observed between parental species and hybrids in subsequent harvest years. Comparison of above‐ and below‐ground biomass showed more DM in roots and rhizome of clover in the backcrosses than in the T. repens plots in the second harvest year but differences were less evident in the third harvest year. The clover in the backcross hybrid plots also had fewer stolon growing points per quadrat than the T. repens plots, but the BC2 had more than the BC1 plots. The exploitation of these hybrids in breeding programmes as a strategy to improve the persistence and drought tolerance of white clover is discussed and implications for forage production considered.
Sward height, structure and leaf extension rate of Lolium perenne pastures when grazed by overwintering barnacle geese
Authors: Cope D. R. , Rowcliffe J. M. , Pettifor R. A.
Published: July 2003

Abstract The grazing of agricultural pastures during winter and spring by geese is considered an important agricultural problem in parts of the U.K. This study describes the sward structure, leaf extension and senescence rates of Lolium perenne‐dominated pastures that are frequently grazed by barnacle geese (Branta leucopsis) during winter in South‐west Scotland, as well as the conducting of a field experiment that simulated grazing to investigate the effects of defoliation. Gross leaf extension and senescence rates were strongly related to temperature, daylength and average tiller size, resulting in positive values of net leaf extension rate per tiller for most of the winter. Total tiller length declined from November to January but increased from January to April. Sward height, however, declined consistently from October to April, suggesting that swards were becoming trampled by repeated visits by flocks of geese over this time. The structure of individual tillers was found to vary slightly over the winter, with tillers becoming more dominated by younger leaves towards the end of the winter. Experimental defoliation of tillers suggested that absolute leaf extension rates did not respond in an under‐ or over‐compensatory manner, even when tillers were nearly completely defoliated. The results suggested that sward structure and leaf extension rates are not unduly affected by repeated grazing by overwintering geese and that short‐term depletion and trampling are the main impacts.
The implications of controlling grazed sward height for the operation and productivity of upland sheep systems in the UK: 6. The effect of reducing stocking rate and application of fertilizer nitrogen in Wales
Authors: Sibbald A. R. , Jones J. R. , Maxwell T. J. , Munro J. M. M. , Davies D. A. , Rees M. E. , Fothergill M. , Dalziel A. J. I.
Published: July 2003

Abstract The implications for the agricultural productivity of the UK upland sheep systems of reducing nitrogen fertilizer application and lowering stocking rates on perennial ryegrass/white clover swards were studied over 4 years at a site in Wales. The system involved grazing ewes and lambs from birth to weaning on swards maintained at a constant height with surplus herbage made into silage, thereafter ewes and weaned lambs grazed on separate areas until the onset of winter with adjustments to the size of the areas grazed and utilizing surplus pasture areas for silage. Four stocking rates [SR 18, 15, 12 and 9 ewes ha−1 on the total area (grazed and ensiled)] and two levels of annual nitrogen fertilizer application (N 200 and 50 kg ha−1) were studied in five treatments (N200/SR18, N200/SR15, N50/SR15, N50/SR12 and N50/SR9). Average white clover content was negatively correlated with the level of annual nitrogen fertilizer application. White clover content of the swards was maintained over the duration of the experiment with an increasing proportion of clover in the swards receiving 50 kg N ha−1. Control of sward height and the contribution from white clover resulted in similar levels of lamb liveweight gain from birth to weaning in all treatments but fewer lambs reached the slaughter live weight by September at the higher stocking rates and with the lower level of fertilizer application. Three of the five treatments provided adequate winter fodder as silage (N200/SR15, N50/SR12 and N50/SR9). Because of the failure to make adequate winter fodder and the failure of white clover to fully compensate for reduction in nitrogen fertilizer application, it is concluded that nitrogen fertilizer can only be reduced on upland sheep pastures if accompanied by reduced stocking rates.
Behavioural responses to habitat patch boundaries restrict dispersal and generate emigration–patch area relationships in fragmented landscapes
Authors: Schtickzelle Nicolas , Baguette Michel
Published: July 2003

We studied the consequences of behaviour at habitat patch boundaries on dispersal for the bog fritillary butterflyProclossiana eunomiaEsper in two networks of habitat differing in fragmentation and matrix quality. We tested for differences in responses to patch boundaries according to the fragmentation level of the network by analysing movement paths of adult butterflies.

Butterflies systematically engaged in U‐turns when they reached a boundary in the fragmented network while they crossed over boundaries in more than 40% of boundary encounters in the continuous one.

We applied the Virtual Migration model (Hanski, Alho & Moilanen 2000) to capture–mark–recapture data collected in both networks. The model indicated (i) a lower dispersal rate and (ii) a lower survival during dispersal in the fragmented network. This latter difference is likely to be the key biological process leading to behavioural avoidance of patch boundary crossings.

On the basis of this behavioural difference, we designed an individual‐based simulation model to explore the relationship between patch area, boundary permeability and emigration rate.

Predictions of the model fitted observed results of the effect of patch area on emigration rate according to fragmentation: butterflies are more likely to leave small patches than large ones in fragmented landscapes (where patch boundary permeability is low), while this relationship disappears in more continuous landscapes (where patch boundary permeability is high).
Density‐dependent mortality is mediated by foraging activity for prey fish in whole‐lake experiments
Authors: Biro Peter A. , Post John R. , Parkinson Eric A.
Published: July 2003

Whereas the effects of density‐dependent growth and survival on population dynamics are well‐known, mechanisms that give rise to density dependence in animal populations are not well understood. We tested the hypothesis that the trade‐off between growth and mortality rates is mediated by foraging activity and habitat use. Thus, if depletion of food by prey is density‐dependent, and leads to greater foraging activity and risky habitat use, then visibility and encounter rates with predators must also increase.

We tested this hypothesis by experimentally manipulating the density of young rainbow trout (Oncorhynchus mykiss) at risk of cannibalism, in a replicated single‐factor experiment using eight small lakes, during an entire growing season.

We found no evidence for density‐dependent depletion of daphnid food in the nearshore refuge where most age‐0 trout resided. Nonetheless, the proportion of time spent moving by individual age‐0 trout, the proportion of individuals continuously active, and use of deeper habitats was greater in high density populations than in low density populations. Differences in food abundance among lakes had no effect on measures of activity or habitat use.

Mortality of age‐0 trout over the growing season was higher in high density populations, and in lakes with lower daphnid food abundance. Therefore, population‐level mortality of age‐0 trout is linked to greater activity and use of risky habitats by individuals at high densities. We suspect that food resources were depleted at small spatial and temporal scales not detected by our plankton sampling in the high density treatment, because food‐dependent activity and habitat use by age‐0 trout occurs in our lakes when food abundance is experimentally manipulated (Biro, Post & Parkinson, in press).