bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing of depth‐dependent lithosphere stretching on the S. Lofoten rifted margin offshore mid‐Norway: pre‐breakup or post‐breakup?
Authors: Kusznir N. J. , Hunsdale R. , Roberts A. M. 
Published: December 2004

AbstractDepth‐dependent stretching, in which whole‐crustal and whole‐lithosphere extension is significantly greater than upper‐crustal extension, has been observed at both non‐volcanic and volcanic rifted continental margins. A key question is whether depth‐dependent stretching occurs during pre‐breakup rifting or during sea‐floor spreading initiation and early sea‐floor spreading. Analysis of post‐breakup thermal subsidence and upper‐crustal faulting show that depth‐dependent lithosphere stretching occurs on the outer part of the Norwegian volcanic rifted margin. For the southern Lofoten margin, large breakup lithosphere β stretching factors approaching infinity are required within 100 km of the continent–ocean boundary to restore Lower Eocene sediments and flood basalt surfaces (∼54 Ma) to interpreted sub‐aerial depositional environments at sea level as indicated by well data. For the same region, the upper crust shows no significant Palaeocene and Late Cretaceous faulting preceding breakup with upper‐crustal β stretching factors <1.05. Further north on the Lofoten margin, reverse modelling of post‐breakup subsidence with a β stretching factor of infinity predicts palaeo‐bathymetries of ∼1500 m to the west of the Utrøst Ridge and fails to restore Lower Eocene sediments and flood basalt tops to sea level at ∼54 Ma. If these horizons were deposited in a sub‐aerial depositional environment, as indicated by well data to the south, an additional subsidence event younger than 54 Ma is required compatible with lower‐crustal thinning during sea‐floor spreading initiation. For the northern Vøring margin, breakup lithosphere β stretching factors of ∼2.5 are required to restore Lower Eocene sediments and basalts to sea level at deposition, while Palaeocene and Late Cretaceous upper‐crustal β stretching factors for the same region are < 1.1. The absence of significant Palaeocene and late Cretaceous extension on the southern Lofoten and northern Vøring margins prior to continental breakup supports the hypothesis that depth‐dependent stretching of rifted margin lithosphere occurs during sea‐floor spreading initiation or early sea‐floor spreading rather than during pre‐breakup rifting.
Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature
Authors: Yomtovian Roslyn , Niklinski Waldemar , Silver Bernard , Sarode Ravindra , Tsai Han‐Mou 
Published: December 2004

SummaryDeficiency of von Willebrand factor (VWF) cleaving protease ADAMTS13 has been demonstrated to be the proximate cause of a subset of thrombotic microangiopathic haemolytic anaemias (MAHA) typical for thrombotic thrombocytopenic purpura (TTP). ADAMTS13 gene mutations cause the hereditary form; acquired deficiency has been attributed to presence of an autoantibody, which may represent a specific subset of MAHA best termed ‘autoimmune thrombotic thrombocytopenic purpura’. We describe a patient with relapsing TTP because of ADAMTS13 inhibitors, who failed to achieve sustained remission despite therapies with plasma exchange, steroids, vincristine, staphylococcal protein A and splenectomy. The ADAMTS13 inhibitor titre remained elevated and clinical stability was only maintained by plasma exchange every 2–3 d over a period of 268 d. The patient then received rituximab therapy (eight doses of 375 mg/m2 weekly), during which she required five plasma exchanges in the first 10 d, two exchanges in the next 3 weeks, and none thereafter for 450 d and ongoing. The ADAMTS13 inhibitor titre decreased and enzyme activity increased. We compared this case with that of seven previously reported TTP cases also treated with rituximab; experience suggests that rituximab therapy deserves further investigation for patients with either refractory or relapsing TTP caused by ADAMTS13 inhibitors.
Favourable results with a single autologous stem cell transplant following conditioning with busulphan and cyclophosphamide in patients with multiple myeloma
Authors: Toor Amir A. , Ayers John , Strupeck Joan , Parthasarathy Mala , Creech Steve , Rodriguez Tulio , Stiff Patrick J. 
Published: December 2004

SummaryBoth single and tandem cycles of high dose therapy and autologous peripheral blood stem cell transplantation (ASCT) have been shown to improve survival in multiple myeloma (MM) patients. We report outcomes in 104 MM patients undergoing a single transplant after conditioning with a conventional myeloablative regimen, busulphan and cyclophosphamide. The patients were either in a first (71%), or subsequent remission (29%). Peripheral blood stem cells were mobilized using cyclophosphamide and granulocyte colony stimulating factor. The conditioning regimen consisted of busulphan 0·85 mg/kg given orally every 6 h (16 doses) and cyclophosphamide 60 mg/kg/d given intravenously for 2 d. The entire conditioning, transplant and post‐transplant course were in the outpatient setting for 45% patients. At a median follow‐up of 26 months (range 2–98 months), the median overall and progression‐free survival were 57 months [95% confidence interval (CI) 47–68] and 26 months (95% CI 20–32) respectively. Younger age and higher CD34+cell dose infused were independently predictive of improved overall and progression‐free survival. Busulphan and cyclophosphamide is an effective and well‐tolerated preparative regimen for ASCT that can be given to MM patients in the outpatient setting.
Single nucleotide polymorphisms of the inflammatory cytokine genes in adults with chronic immune thrombocytopenic purpura
Authors: Satoh Takashi , Pandey Janardan P. , Okazaki Yuka , Yasuoka Hidekata , Kawakami Yutaka , Ikeda Yasuo , Kuwana Masataka 
Published: December 2004

SummarySingle nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were examined in 84 adult Japanese patients with chronic immune thrombocytopenic purpura (ITP) and 56 race‐matched healthy controls. The SNPs examined were within the genes encoding tumour necrosis factor (TNF)‐α (−238 G/A and −308 G/A), TNF‐β (+252 G/A), and interleukin (IL)‐1β (−511 C/T and +3953 T/C). Of these SNPs, the frequency of the TNF‐β (+252) G/G phenotype was significantly higher in ITP patients than in healthy controls (21% vs. 7%, P = 0·04, odds ratio = 3·6, 95% confidence interval 1·1–11·1), while no significant association was detected for the other SNPs. The distribution of the TNF‐β (+252) phenotype was not associated with human leucocyte antigen class II alleles or the therapeutic response in ITP patients. The frequency of circulating anti‐glycoprotein IIb/IIIa antibody‐producing B cells was significantly higher in ITP patients with the TNF‐β (+252) G/G phenotype than in those with the G/A or A/A phenotype (11·9 ± 4·9 vs. 6·8 ± 4·9 and 3·7 ± 2·8 per 105 peripheral blood mononuclear cells; P = 0·02 and P < 0·001, respectively). These findings suggest that the SNP located at TNF‐β (+252) contributes to susceptibility to chronic ITP by controlling the autoreactive B‐cell responses to platelet membrane glycoproteins.
Abnormal LTC4 synthase RNA degradation in neutrophils from CML patients
Authors: Roos Cecilia , Sjölinder Mikael , Stenke Leif , Tornhamre Susanne 
Published: December 2004

SummaryNeutrophils from patients with chronic myeloid leukaemia (CML) have an aberrant expression of leukotriene (LT)C4 synthase. In order to learn more about the regulation of this abnormality, LTC4 synthase mRNA expression was determined by reverse transcription polymerase chain reaction. A digoxigenin (DIG)‐labelled LTC4 synthase RNA was synthesized and incubated in cytsolic extracts from CML neutrophils, normal neutrophils and eosinophils. LTC4 synthase mRNA was detected in total but not cytoplasmic RNA from normal neutrophils. In contrast, LTC4 synthase mRNA was found in the cytoplasm of CML neutrophils and in normal eosinophils, which also express the enzyme. The DIG‐labelled LTC4 synthase RNA was, as opposed to normal neutrophils, degraded in cytosolic extracts from CML neutrophils. The degradation was time dependent and cell concentration dependent. Degradation was also seen in eosinophils, indicating that degradation of LTC4 synthase RNA was correlated to the expression of the protein. This study showed that the difference in expression of LTC4 synthase in normal and CML neutrophils was not because of a total lack of LTC4 synthase mRNA in normal neutrophils. However normal neutrophils lack, in contrast to CML neutrophils, LTC4 synthase mRNA in the cytoplasm. This discrepancy is not caused by a stabilized LTC4 synthase RNA in the cytosol of CML neutrophils. Instead an abnormal degradation of LTC4 synthase RNA was found in the cytosol of CML neutrophils.
Clinical follow‐up indicates differential accuracy of magnetic resonance imaging and immunocytology of the cerebral spinal fluid for the diagnosis of neoplastic meningitis – a single centre experience
Authors: Zeiser Robert , Burger Jan A. , Bley Thorsten A. , Windfuhr‐Blum Marissa , Schulte‐Mönting Jürgen , Behringer Dirk M. 
Published: December 2004

SummaryIn patients with neoplastic meningitis (NM), the rapid institution of intrathecal therapy may ameliorate the course of disease, indicating that a timely diagnosis is clinically relevant. As immunocytology (IC) of cerebrospinal fluid and magnetic resonance imaging (MRI), as diagnostic methods, have potential pitfalls, the present study assessed the results of both methods, to determine the predictive capability of the initial evaluations with respect to the risk that the patient would develop NM during the course of their disease. A total of 166 individuals with B‐cell non‐Hodgkin's lymphoma (B‐NHL; n = 95), B‐acute lymphocytic leukaemia (ALL; n = 18), acute myeloid leukaemia (n = 27) or solid tumours (n = 26), with at least one definitive IC and MRI result within 3 weeks, were evaluated at a median follow‐up of 29·5 months (range 6–53 months). IC and MRI results reached the highest concordance (98%) in B‐NHL patients and were most discordant in ALL patients (43%). In haematological malignancies, IC displayed considerable sensitivity, ranging from 89% to 95%, while MRI had very low sensitivity. Conversely, MRI showed high sensitivity (100%) and specificity (92%) in solid tumours. We conclude that IC is of particular value in the diagnosis of NM due to haematological malignancies while MRI is superior to IC in the diagnosis of NM due to solid tumours.
In vivo and in vitro effects of different anaesthetics on platelet function
Authors: Dordoni Pier Lorenza , Frassanito Luciano , Bruno Maria F. , Proietti Rodolfo , Cristofaro Raimondo De , Ciabattoni Giovanni , Ardito Guglielmo , Crocchiolo Roberto , Landolfi Raffaele , Rocca Bianca 
Published: December 2004

SummaryDifferent effects of thiopental, propofol and sevoflurane on platelets have been reported. Patients undergoing thyroid surgery were anaesthetized with thiopental–fentanyl–sevoflurane (n = 11) or propofol–fentanyl–sevoflurane (n = 9). Platelet aggregation and thromboxane A2 generation were studied at baseline, and at the end of anaesthesia induction and surgery. Dose–response experiments were also performed in vitro with single agents. Thiopental–fentanyl–sevoflurane significantly reduced collagen‐induced aggregation by the end of induction, while ADP‐induced aggregation and thromboxane generation were unaffected. Propofol–fentanyl–sevoflurane had no effect on platelets. Thiopental dose‐dependently inhibited platelets in vitro, while fentanyl or propofol did not. In conclusion, thiopental reduces platelet function both ex vivo and in vitro and propofol might be considered haemostatically safer.
T cell recognition of bcr/abl in healthy donors and in patients with chronic myeloid leukaemia
Authors: Westermann Jörg , Schlimper Claudia , Richter Günther , Mohm Johannes , Dörken Bernd , Pezzutto Antonio 
Published: December 2004

SummaryIn chronic myeloid leukaemia (CML), peptides from the fusion region of bcr3/abl2 are likely to play a role in anti‐leukaemic T cell immunity. We investigated whether T cells that recognize bcr/abl fusion peptides could be detected in healthy donors and CML patients. T cell responses against bcr3/abl2 fusion peptides were analysed by γ‐interferon enzyme‐linked immunospot assays after prestimulation of peripheral blood mononuclear cells in the presence of anti‐CD3‐antibodies and interleukin‐2. Our results suggest that the T cell repertoire contains bcr3/abl2‐reactive T cells in CML patients who are in cytogenetic remission, but also in some healthy individuals.
The role of matrix metalloproteinase 9 in the pathogenesis of chronic lymphocytic leukaemia
Authors: Kamiguti Aura S. , Lee Edwin S. , Till Kathleen J. , Harris Robert J. , Glenn Mark A. , Lin Ke , Chen Hai Juan , Zuzel Mirko , Cawley John C. 
Published: December 2004

SummaryMatrix metalloproteinases (MMPs) are important for the pathogenesis and progression of different tumours. MMPs‐2 and ‐9 are the principal MMPs produced by lymphocytes; these enzymes can degrade a number of matrix proteins but are the two main MMPs that digest type IV collagen, the major component of basement membranes. Therefore, these enzymes are potentially important for tissue invasion and remodelling by malignant lymphocytes. This study showed that chronic lymphocytic leukaemia (CLL) cells produce and secrete variable amounts of pro‐MMP‐9, but no MMP‐2 or tissue inhibitor of metalloproteinase 1 (TIMP‐1). The pro‐enzyme was found in monomeric and dimeric forms and also complexed with lipocalin. Moreover, a small fraction of secreted monomer became associated with the cell surface and activated upon cell adhesion to insolubilized type IV collagen. High levels of intracellular MMP‐9 were associated with advanced (stage C) disease and with poor patient survival. Immunohistochemical studies demonstrated that MMP‐9 was associated with areas of tissue invasion and remodelling. The relatively specific MMP‐9 inhibitors, Ro31‐9790 (3 μmol/l) and TIMP‐1, reduced CLL‐cell migration through type IV collagen and through endothelial monolayers suggesting that the enzyme may also be important in malignant cell entry and egress to and from involved tissue. Our data raise the possibility that MMP‐9 modulation may have therapeutic potential in advanced CLL.
Early response predicts thalidomide efficiency in patients with advanced multiple myeloma*
Authors: Waage Anders , Gimsing Peter , Juliusson Gunnar , Turesson Ingemar , Gulbrandsen Nina , Eriksson Tommy , Hjorth Martin , Nielsen Johan Lanng , Lenhoff Stig , Westin Jan , Wislöff Finn ,   for the Nordic Myeloma Study Group
Published: December 2004

SummarySixty‐five patients who were primary or secondary refractory to melphalan/prednisone or other type of chemotherapy, or relapsed within 6 months after high dose chemotherapy with stem cell support, were given thalidomide at a dose of 200 mg/d escalating to 800 mg. The patients were followed for a median of 2 years and 22 weeks. Response was evaluated according to M‐protein reduction combined with improvement of haemoglobin (Hb) concentration, renal function and pain. Altogether, 14% of patients had a minor response, 14% partial response and 6% complete response. Median survival was 12 months and 29% were alive at last contact. Decline of M protein started early and a minimum 25% reduction of M protein was detected in 14 of 20 responders (70%) after 3 weeks, and in 20 of 22 responders (91%) after 5 weeks of treatment. Reduction of M protein continued for 3 months and further decline was observed in only four patients. The Hb concentration showed a different time course, with a significant increase after 3 months and further increases continued for up to 12 months. Blood concentration levels of thalidomide from 40 patients were used to evaluate the pharmacokinetics of the drug. Rate of absorption, rate of elimination, volume of distribution, clearance and elimination half‐life were calculated to be 0·200/h, 0·140/h, 0·886 l/kg, 0·126 l/h/kg and 4·98 h respectively. We found no relationship between thalidomide concentration and effect after 12 weeks.
Diamond Blackfan anaemia in the UK: clinical and genetic heterogeneity
Authors: Orfali Karen A. , Ohene‐Abuakwa Yaw , Ball Sarah E. 
Published: December 2004

SummaryA detailed family study was undertaken of patients notified to the UK Diamond Blackfan Anaemia (DBA) Registry. RPS19 mutations were detected in 16 of 104 families, including two patients with deletions detected by intragenic loss of heterozygosity of tightly linked polymorphisms. In two further cases, polymorphisms were used to determine the parental allele of origin of RPS19 point mutations. A review of clinical details of patients with mutations and patients in the literature having identical or equivalent mutations revealed evidence for a genotype:phenotype correlation with respect to the prevalence of physical anomalies, and the occurrence of mild or variable haematological severity. Nine of 60 patients had a known family history of DBA. Haematological abnormalities, including raised red cell adenosine deaminase activity, were found in first‐degree relatives of 16 of 51 (31%) of patients not previously considered to have familial DBA. Results of both parents and any siblings were normal in only 35 of 60 (58%) of cases, who were therefore assumed to have sporadic de novo DBA. The classical inheritance pattern for DBA is autosomal dominant; however, 12 of 60 families (20%) had more than one affected child despite normal results in both parents. These results have important implications for genetic counselling, and for the selection of potential sibling bone marrow donors.
α‐Galactosylceramide‐driven expansion of human natural killer T cells is inhibited by prednisolone treatment
Authors: Johansson Ulrika , Macey Marion G. , Kenny Deborah , Provan Drew , Newland Adrian C 
Published: December 2004

SummaryThe mechanisms of action of most treatments in the autoimmune disorders are unclear and steroids remain the first‐line therapy in these diseases. Natural killer T (NKT) cell activity has been implicated in the autoimmune process but whether steroids act via an affect on NKT cell function, such as antigen‐specific proliferative capacity, is unknown. Immune thrombocytopenia (ITP) patients were studied ex vivo for NKT cell expansion in response to the specific NKT cell antigen, α‐galactosylceramide, before, during or after prednisolone treatment. Prednisolone inhibited antigen‐specific NKT cell expansion in ITP patients in remission. Untreated ITP patients also showed reduced NKT cell proliferative capacity, although this was less marked than in treated patients. These results support a role for NKT cells in ITP and aid understanding of the immunosuppressive activities of prednisolone in autoimmune disease.
Haematopoietic stem cell transplantation with non‐myeloablative conditioning in the outpatient setting: results, complications and admission requirements in a single institution
Authors: Petersen Søren L. , Madsen Hans O. , Ryder Lars P. , Svejgaard Arne , Jakobsen Bodil K. , Sengeløv Henrik , Heilmann Carsten , Dickmeiss Ebbe , Vindeløv Lars L. 
Published: December 2004

SummaryThirty patients with haematological malignancies received peripheral blood stem cells from human leucocyte antigen (HLA)‐identical sibling donors after non‐myeloablative conditioning with fludarabine and total body irradiation. Twenty‐seven patients received the transplant as an outpatient procedure. All patients engrafted. The probability of acute graft‐versus‐host disease (GVHD) grades II–IV and extensive chronic GVHD was 57% and 80%, respectively. Patients alive on day +365 experienced a median of 44 d (range 4–151) of hospitalization during the first year. In the entire cohort, GVHD accounted for 22%, infections for 18%, thrombotic thrombocytopenic purpura (TTP) for 16% and engraftment syndrome for 14% of the time in hospital. The 1‐year risk of TTP was 26%. Acute GVHD was a risk factor for the development of TTP (P = 0·008). With a median follow‐up of 602 d, the 2‐year estimates for overall survival, progression‐free survival, non‐relapse mortality and relapse related mortality were 68%, 43%, 22% and 13%, respectively. This transplantation regimen is feasible and induces long‐term remissions in heavily pretreated patients. The procedure can be performed in the outpatient setting, but complications could result in a substantial number of admissions during the first year.
No deterioration after 13 years in a stability study of a rabbit brain, plain, thromboplastin, RBT 1010, in rubber‐stoppered ampoules
Authors: Stevenson K. J. , Craig S. , Goodman L. , Kanyike F. B. 
Published: December 2004

SummaryRBT 1010, a rabbit brain thromboplastin, plain, was prepared at the Thrombosis Reference Centre, Withington Hospital, Manchester, in 1989. The batch has been stored at −20°C, in rubber‐stoppered ampoules, for 13 years. The material was unchanged after this time. This was confirmed in a stability study, in which the reagent was used to test the prothrombin times of a panel of plasmas stored in liquid nitrogen, one from a normal volunteer and two from stable anticoagulated patients. RBT 1010 was also tested in calibrations, according to World Health Organization recommendations, against the reference thromboplastin preparations CRM 149S and RBT 90.
The Bcl‐2 family member Bfl‐1/A1 is strongly repressed in normal and malignant plasma cells but is a potent anti‐apoptotic factor for myeloma cells
Authors: Tarte Karin , Jourdan Michel , Veyrune Jean Luc , Berberich Ingolf , Fiol Geneviève , Redal Nicole , Shaughnessy John , Klein Bernard 
Published: December 2004

SummaryTerminal B‐cell differentiation is a multi‐step process, from short‐lived plasmablasts to mature long‐lived plasma cells (PC). The anti‐apoptotic Bcl‐2 family member Bfl‐1/A1 plays a critical role in the survival of mature B cells. However, its potential involvement at the later stages of B‐cell development remains highly controversial. Our aim was thus to clarify the place of Bfl‐1/A1 in the biology of normal PC and in the pathogenesis of multiple myeloma (MM), the major PC dyscrasia. Using gene expression profiling and quantifiable reverse transcription polymerase chain reaction experiments, we found a similar down‐regulation of Bfl‐1/A1 in both normal immature plasmablasts and mature PC when compared with B cells. In myeloma cells, the level of Bfl‐1/A1 was low and Bfl‐1/A1 was not a nuclear factor κB‐inducible gene. Collectively, these data demonstrate that Bfl‐1/A1 is not involved in the prolonged survival of normal mature PC, and that Bfl‐1/A1 deregulation is not a common oncogenic event in MM. However, overexpression of Bfl‐1/A1 by retroviral transduction promoted autonomous survival of an interleukin‐6‐dependent myeloma cell line and rendered it less sensitive to dexamethasone. Thus, Bfl‐1/A1 transduction could be an interesting tool to obtain myeloma cell lines from primary samples and to favour the in vitro generation of antibody‐secreting, long‐lived normal PC.