bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Arabidopsis Rab GTPase RabA4b Localizes to the Tips of Growing Root Hair Cells[W]
Authors: Preuss Mary L. , Serna Jannie , Falbel Tanya G. , Bednarek Sebastian Y. , Nielsen Erik 
Published: June 2004

AbstractSpatial and temporal control of cell wall deposition plays a unique and critical role during growth and development in plants. To characterize membrane trafficking pathways involved in these processes, we have examined the function of a plant Rab GTPase, RabA4b, during polarized expansion in developing root hair cells. Whereas a small fraction of RabA4b cofractionated with Golgi membrane marker proteins, the majority of this protein labeled a unique membrane compartment that did not cofractionate with the previously characterized trans-Golgi network syntaxin proteins SYP41 and SYP51. An enhanced yellow fluorescent protein (EYFP)-RabA4b fusion protein specifically localizes to the tips of growing root hair cells in Arabidopsis thaliana. Tip-localized EYFP-RabA4b disappears in mature root hair cells that have stopped expanding, and polar localization of the EYFP-RabA4b is disrupted by latrunculin B treatment. Loss of tip localization of EYFP-RabA4b was correlated with inhibition of expansion; upon washout of the inhibitor, root hair expansion recovered only after tip localization of the EYFP-RabA4b compartments was reestablished. Furthermore, in mutants with defective root hair morphology, EYFP-RabA4b was improperly localized or was absent from the tips of root hair cells. We propose that RabA4b regulates membrane trafficking through a compartment involved in the polarized secretion of cell wall components in plant cells.
Anti‐sickling effect of MX‐1520, a prodrug of vanillin: an in vivo study using rodents
Authors: Zhang Chaojie , Li Xiang , Lian Lurong , Chen Qiukan , Abdulmalik Osheiza , Vassilev Vasco , Lai Ching‐San , Asakura Toshio 
Published: June 2004

SummaryVanillin, a food additive, covalently binds with sickle haemoglobin (Hb S), inhibits cell sickling and shifts the oxygen equilibrium curve towards the left. These effects would potentially benefit patients with sickle cell disease (SCD). However, vanillin has no therapeutic effect if given orally because orally administered vanillin is rapidly decomposed in the upper digestive tract. To overcome this problem, a vanillin prodrug, MX‐1520, which is biotransformed to vanillin in vivo, was synthesized. Studies using transgenic sickle mice, which nearly exclusively develop pulmonary sequestration upon exposure to hypoxia, showed that oral administration of MX‐1520 prior to hypoxia exposure significantly reduced the percentage of sickled cells in the blood. The survival time under severe hypoxic conditions was prolonged from 6·6 ± 0·8 min in untreated animals to 28·8 ± 12 min (P < 0·05) and 31 ± 7·5 min (P < 0·05) for doses of 137·5 and 275 mg/kg respectively. Intraperitoneal injection of MX‐1520 to bypass possible degradation in the digestive tract showed that doses as low as 7 mg/kg prolonged the survival time and reduced the percentage of sickled cells during hypoxia exposure. These results demonstrate the potential for MX‐1520 to be a new and safe anti‐sickling agent for patients with SCD.
Adverse prognostic significance of CD20 positive Reed–Sternberg cells in classical Hodgkin's disease*
Authors: Portlock Carol S. , Donnelly Gerard B. , Qin Jing , Straus David , Yahalom Joachim , Zelenetz Andrew , Noy Ariela , O'Connor Owen , Horwitz Steven , Moskowitz Craig , Filippa Daniel A. 
Published: June 2004

SummaryThe prognostic significance of CD20 positive classical Hodgkin's disease (cHD) is uncertain. All cHD cases referred to the Memorial Sloan–Kettering Cancer Center (MSKCC) were retrospectively identified (5/92–11/00); the samples were immunostained, and clinical data ascertained. Cases were re‐reviewed without knowledge of clinical outcome. Univariate and multivariate analyses were performed 248 patients had cHD: 28 CD20+ (11%); 220 CD20−. All clinical characteristics were comparable except haemoglobin level at presentation. With a median follow‐up of 29·2 months, significant prognostic factors in multivariate analysis were: CD20 positivity, elevated white blood cell count (WBC) and low absolute lymphocyte count for time‐to treatment failure (TTF); and for overall survival (OS), CD20 positivity, elevated WBC count, bone marrow involvement and age ≥45 years. TTF was significantly poorer for ABVD‐treated patients with CD20+ cHD as compared with CD20− cHD. Among 167 patients treated at MSKCC, both TTF (P < 0·0001) and OS (P = 0·017) were significantly decreased in CD20+ patients as compared with CD20− cHD. CD20+ cHD is a poor prognostic factor for TTF and OS. All cHD cases should be immunophenotyped for CD20. A large prospective trial is needed to confirm these findings.
Four new cases of stomatin‐deficient hereditary stomatocytosis syndrome: association of the stomatin‐deficient cryohydrocytosis variant with neurological dysfunction
Authors: Fricke Britta , Jarvis Helen G. , Reid Cecil D. L. , Aguilar‐Martinez Patricia , Robert A. , Quittet P. , Chetty Margaret , Pizzey Arnold , Cynober Thérèse , Lande William F. , Mentzer William C. , von Düring Monika , Winter Stuart , Delaunay Jean , Stewart Gordon W. 
Published: June 2004

SummaryThis report concerns congenitally Na+–K+ leaky red cells of the ‘hereditary stomatocytosis’ class. Three new isolated cases and one new pedigree are described, and one previously reported case is expanded. In all cases, Western blotting of red cell membranes revealed a deficiency in the 32 kDa membrane protein, stomatin. All showed pronounced cation leaks at 37°C with markedly abnormal intracellular Na+ and K+ concentrations, like all other such stomatin‐deficient cases. Consistent with recent findings in two previously described British pedigrees, immunocytochemistry demonstrated that the deficiency of stomatin was not complete. On typical blood films, some red cells showed positive stomatin immunoreactivity, while most were negative, although in one case only a minority were negative. All platelets and neutrophils were stomatin positive. The cases differed markedly between themselves with regard to the temperature dependence of the passive leak to K+. Three showed a simple monotonic temperature dependence, while two showed a minimum at around 20–25°C, such that the cells were extremely leaky at 0°C, giving the phenotype known as ‘cryohydrocytosis’. These patients are the only two known cases of stomatin‐deficient cryohydrocytosis. Both showed a congenital syndrome of mental retardation, seizures, cataracts and massive hepatosplenomegaly, probably defining a new haemato‐neurological syndrome.
Novel loss‐of‐function mutations of the haematopoiesis‐related transcription factor, acute myeloid leukaemia 1/runt‐related transcription factor 1, detected in acute myeloblastic leukaemia and myelodysplastic syndrome
Authors: Nakao Mitsushige , Horiike Shigeo , Fukushima‐Nakase Yoko , Nishimura Motohiro , Yasuko Fujita  , Taniwaki Masafumi , Okuda Tsukasa 
Published: June 2004

Summary AML1/RUNX1, which encodes a transcription factor essential for definitive haematopoiesis, is a frequent target of leukaemia‐associated chromosome translocations. Point mutations of this gene have also recently been associated with leukaemia and myelodysplastic syndrome (MDS). To further define the frequency and biological characteristics of AML1 mutations, we have examined 170 cases of such diseases. Mutations within the runt‐domain were identified in five cases: one of de novo acute myeloid leukaemia (AML) and four of MDS. Where multiple time point samples were available, mutations were detected in the earliest samples, which persisted throughout the disease course. Of the five mutations, one was a silent mutation, two were apparent loss‐of‐function mutations caused by N‐terminal truncation, and two were insertions, I150ins and K168ins, which preserved most of the AML1 DNA‐binding domain. Both AML1 molecules with insertion mutations were non‐functional in that they were unable to rescue haematological defects in AML1‐deficient mouse embryonic stem cells. In addition, activating mutations of N‐ras, deletion of chromosome 12p, or inactivation of TP53 accompanied some of the AML1 mutations. Together, these observations strongly suggest that one‐allele inactivation of AML1 serves as an initial or early event that plays an important role in the eventual development of overt diseases with additional genetic alterations.
Interest of transjugular liver biopsy in adult patients with haemophilia or other congenital bleeding disorders infected with hepatitis C virus
Authors: Stieltjes Natalie , Ounnoughene Nadra , Sava Emilie , Paugy Patricia , Roussel‐Robert Valérie , Rosenberg Arielle R. , Terris Benoit , Salmon‐Céron Dominique , Sogni Philippe 
Published: June 2004

SummaryLiver histology is important for prognosis and treatment strategy in patients with hepatitis C. We report a 10‐year experience of transjugular liver biopsy (TJLB) in patients with haemophilia and other congenital bleeding disorders (CBD) in terms of safety, efficiency and therapeutic consequences. TJLB was proposed to patients who were regularly followed for CBD, and were hepatitis C virus (HCV) positive by polymerase chain reaction. Patients with inhibitors or who were human immunodeficiency virus (HIV) positive with CD4 cells <0·2 × 109/l or with evidence of liver failure were excluded. TJLB was performed during a short hospitalization with factor replacement. Between 1992 and 2002, 88 TJLB were performed in 69 of 151 adult HCV patients (39% HIV positive). CBD was haemophilia A in 68% and haemophilia B in 24%. Few mild adverse events were recorded. Histology was assessable in 78 of 88 procedures (89%). Twenty‐nine (37%) cases demonstrated minimal change (METAVIR A ≤ 1 and F ≤ 1). Extended fibrosis or cirrhosis was recorded in 23 procedures (26%), all in patients whose infection period was longer than 20 years. No relationship between liver histology, HIV status or HCV genotype was found. TJLB appears to be safe and useful in HCV patients with CBD. One‐third of patients had minimal histological changes and could avoid systematic anti‐HCV treatment.
Phenotypic and functional characterization of monocyte‐derived dendritic cells in chronic lymphocytic leukaemia patients: influence of neoplastic CD19+ cells in vivo and in vitro
Authors: Orsini Enrica , Pasquale Alessia , Maggio Roberta , Calabrese Elisabetta , Mauro Francesca Romana , Giammartini Elena , Guarini Anna , Foa Robin 
Published: June 2004

SummaryDendritic cells (DCs) are the most potent antigen‐presenting cells and are therefore an attractive option as antigen carriers in vaccination protocols. Chronic lymphocytic leukaemia (CLL) represents a potential good target for these approaches. The present study was designed to investigate the feasibility of generating in vitro fully functional DCs from peripheral blood (PB) monocytes of CLL patients at different phases of the disease. Although functional DCs could be obtained from CLL samples, in patients with active disease the expression of some co‐stimulatory molecules appeared to be reduced. In contrast, DCs from CLL patients in remission showed no difference from those of normal controls. Moreover, patients with active disease produced DCs with reduced allostimulatory ability when compared with normal ones, whereas the functional capacities appeared to be restored in CLL DCs from remission patients. To more precisely assess the possible inhibitory effect of CLL cells on DC development, the influence of autologous leukaemic CD19+ cells on the generation of monocyte‐derived CLL DCs in vitro was investigated. The addition of CLL neoplastic cells markedly affected monocyte‐derived DC maturation. In conclusion, monocytes from CLL patients with active disease give rise to DCs, which show phenotypic and functional defects that are not observed in remission CLL patients. These results need to be taken into account in the design of DC‐based immunotherapeutic approaches in CLL.
Elevated circulating endothelial membrane microparticles in paroxysmal nocturnal haemoglobinuria
Authors: Simak Jan , Holada Karel , Risitano Antonio M. , Zivny Jan H. , Young Neal S. , Vostal Jaroslav G. 
Published: June 2004

SummaryWe analysed endothelial cell membrane microparticles (ECMP) in the peripheral blood of patients with paroxysmal nocturnal haemoglobinuria (PNH) (n = 9), aplastic anaemia (AA) (n = 10), sickle cell disease (SCD) (n = 8), and healthy donors (HD) (n = 11). There was no clinically manifested thrombosis in the PNH or AA group, except one cured thrombophlebitis (PNH), while all SCD patients had a history of vaso‐occlusive crises. We used three‐colour flow cytometry with blood cell‐specific antibodies and antibodies to endothelial antigens CD105 and CD144. Phosphatidylserine‐positive microparticles were detected using the annexin V‐binding (AVB) assay. The population of CD105+AVB+ ECMP was significantly (P < 0·05) higher in SCD (median: 0·568 × 109/l; 25–75th percentile range: 0·351–0·976 × 109/l) and PNH (0·401 × 109/l ; 0·19–0·441 × 109/l) patients when compared with AA (0·122 × 109/l; 0·061–0·172 × 109/l) or HD (0·180 × 109/l; 0·137–0·217 × 109/l) group. Even more pronounced differences were observed in ECMP exhibiting a marker of inflammatory stimulation CD54 (CD105+CD54+). Similarly, ECMP that exhibited endothelial specific and proteolysis‐sensitive antigen CD144 were increased in SCD and PNH, but not in AA. Elevated CD54+ ECMP may reflect the inflammatory status of endothelial cells in SCD and PNH, while CD144+ ECMP could indicate continuous endothelial stimulation and/or injury. Analysis of circulating ECMP appears promising to provide useful information on the status of the vascular endothelium in PNH and SCD.
Etoposide, methylprednisolone, cytarabine and cisplatin successfully cytoreduces resistant myeloma patients and mobilizes them for transplant without adverse effects
Authors: D'Sa Shirley , Yong Kwee , Kyriakou Chara , Bhattacharya Soumo , Peggs Karl S. , Foulkes Barbara , Watts Michael J. , Ings Stuart J. , Ardeshna Kirit M. , Goldstone Anthony H. , Williams Catherine D. 
Published: June 2004

SummaryMyeloma remains incurable with a median survival of 4 years, but outcome can be improved by the use of high‐dose therapy. We used the etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) regimen as second‐line therapy in 42 newly diagnosed myeloma patients who had failed vincristine, adriamycin and dexamethasone (VAD)‐ type therapy (n = 36), responded to first‐line treatment but persisted in having significant residual marrow plasmacytosis (n = 5) or failed prior stem cell harvesting (n = 1), with the dual aim of improving disease response and mobilizing peripheral blood stem cells. Fourteen of 21 (67%) patients with no change or progressive disease after VAD responded to ESHAP; seven of 12 (58%) patients with minor response converted to partial response. Marrow plasmacytosis fell from a median of 52% at diagnosis to 23·5% after primary therapy and to15% after ESHAP. ESHAP chemotherapy was well‐tolerated. There were 11 admissions due to febrile neutropenia (n = 7), nausea and vomiting (n = 2), pneumonia (n = 1) and perforated bowel (n = 1). Renal function deteriorated in 13 of 42 patients after ESHAP, but none required renal support. ESHAP mobilization was performed in 32 patients of whom 87% achieved a CD34+ yield >2 × 106/kg. In all, 38 patients proceeded to high‐dose therapy. The overall survival for all patients was 62% at 4 years following ESHAP. We conclude that ESHAP has acceptable toxicity and efficient stem cell mobilizing capability, effectively cytoreduced this chemoresistant group of patients, and did not appear to adversely affect transplant outcome.
Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down's syndrome, revealing PRAME as a specific discriminating marker
Authors: McElwaine Suzanne , Mulligan Claire , Groet Jürgen , Spinelli Monica , Rinaldi Andrea , Denyer Gareth , Mensah Afua , Cavani Simona , Baldo Chiara , Dagna‐Bricarelli Franca , Hann Ian , Basso Giuseppe , Cotter Finbarr E. , Nizetic Dean 
Published: June 2004

SummaryTransient myeloproliferative disorder (TMD) is a unique, spontaneously regressing neoplasia specific to Down's syndrome (DS), affecting up to 10% of DS neonates. In 20–30% of cases, it reoccurs as progressive acute megakaryoblastic leukaemia (AMKL) at 2–4 years of age. The TMD and AMKL blasts are morphologically and immuno‐phenotypically identical, and have the same acquired mutations in GATA1. We performed transcript profiling of nine TMD patients comparing them with seven AMKL patients using Affymetrix HG‐U133A microarrays. Similar overall transcript profiles were observed between the two conditions, which were only separable by supervised clustering. Taqman analysis on 10 TMD and 10 AMKL RNA samples verified the expression of selected differing genes, with statistical significance (P < 0·05) by Student's t‐test. The Taqman differences were also reproduced on TMD and AMKL blasts sorted by a fluorescence‐activated cell sorter. Among the significant differences, CDKN2C, the effector of GATA1‐mediated cell cycle arrest, was increased in AMKL but not TMD, despite the similar level of GATA1. In contrast, MYCN (neuroblastoma‐derived oncogene) was expressed in TMD at a significantly greater level than in AMKL. MYCN has not previously been described in leukaemogenesis. Finally, the tumour antigen PRAME was identified as a specific marker for AMKL blasts, with no expression in TMD. This study provides markers discriminating TMD from AMKL‐M7 in DS. These markers have the potential as predictive, diagnostic and therapeutic targets. In addition, the study provides further clues into the pathomechanisms discerning self‐regressive from the progressive phenotype.
Either interleukin‐12 or interferon‐γ can correct the dendritic cell defect induced by transforming growth factor β1 in patients with myeloma
Authors: Brown Ross , Murray Allan , Pope Belinda , Sze Daniel M. , Gibson John , Joy Ho P. , Hart Derek , Joshua Doug 
Published: June 2004

SummaryThe poor response to immunotherapy in patients with multiple myeloma (MM) indicates that a better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed. Recently we reported that high potency (CMRF44+) dendritic cells (DC) in the peripheral blood of patients with MM failed to significantly up‐regulate the expression of the B7 co‐stimulatory molecules, CD80 and CD86, in response to an appropriate signal from soluble trimeric human CD40 ligand. This defect was caused by transforming growth factor β1 (TGFβ1) and interleukin (IL)‐10, produced by malignant plasma cells, and the defect was neutralized in vitro with anti‐TGFβ1. As this defect could impact on immunotherapeutic strategies and may be a major cause of the failure of recent trials, it was important to identify a more clinically useful agent that could correct the defect in vivo. In this study of 59 MM patients, the relative and absolute numbers of blood DC were only significantly decreased in patients with stage III disease and CD80 up‐regulation was reduced in both stage I and stage III. It was demonstrated that both IL‐12 and interferon‐γ neutralized the failure to stimulate CD80 up‐regulation by huCD40LT in vitro. IL‐12 did not cause a change in the distribution of DC subsets that were predominantly myeloid (CD11c+ and CDw123−) suggesting that there would be a predominantly T‐helper cell type response. The addition of IL‐12 or interferon‐γ to future immunotherapy trials involving these patients should be considered.
Low and high circulating cortisol levels predict mortality and cognitive dysfunction early after stroke
Authors: Marklund N. , Peltonen M. , Nilsson T. K. , Olsson T. 
Published: June 2004

Abstract.Objective.  Elevated cortisol levels are associated with confusion and poor outcome after stroke. Dehydroepiandrosterone sulphate (DS), the most abundant adrenal androgen may act as an anti‐glucocorticoid. An altered regulation of these steroids may affect numerous brain functions, including neuronal survival. The purpose of this study was to investigate serum cortisol and DS levels and the cortisol/DS ratio early after stroke and relate our findings to the presence of disorientation and mortality.Design.  Patients with acute ischaemic stroke (n = 88, 56 men and 32 women) admitted to a stroke unit were investigated with repeated clinical assessments and scores for degree of confusion, extent of paresis and level of functioning. Serum cortisol (C) and DS were measured on day 1 and/or day 4. Data for 28‐day and 1‐year mortality are presented. A control group of 65 age‐matched healthy individuals was used. Multivariate analyses of mortality rates in the different tertiles or sixtiles of serum cortisol were performed with logistic regression, adjusting for age, sex, diabetes and level of consciousness.Results.  There was no difference in serum cortisol levels on day 1 for stroke patients when compared with control group values. Initial cortisol levels were significantly higher in the patients with acute disorientation versus orientated patients (P < 0.05). Cortisol levels on day 1 were an independent predictor of 28‐day mortality, and patients with low cortisol levels (<270 nmol L−1) and increased levels (>550 nmol L−1) both had an increased 1‐year mortality. DS levels on day 1 were significantly elevated in stroke patients.Conclusion.  Hypercortisolism is associated with cognitive dysfunction early after ischaemic stroke. High and low circulating cortisol levels are associated with increased mortality after stroke. DS levels were not associated with clinical outcome.
High incidence of type 2 diabetes and increasing conversion rates from impaired fasting glucose and impaired glucose tolerance to diabetes in Mauritius
Authors: Söderberg S. , Zimmet P. , Tuomilehto J. , de Courten M. , Dowse G. K. , Chitson P. , Stenlund H. , Gareeboo H. , Alberti K. G. M. M. , Shaw J. 
Published: June 2004

Abstract.Objective.  To describe the incidence of different stages of glucose intolerance in a population from Mauritius followed over 11 years.Research design, methods and subjects.  Population‐based surveys were undertaken in the multi‐ethnic nation of Mauritius in 1987, 1992 and 1998 with 5083, 6616 and 6291 participants, respectively. Questionnaires, anthropometric measurements, and a 2‐h 75‐g oral glucose tolerance test were included. Three cohorts aged between 25 and 79 years with classifiable glucose tolerance data were identified; 3680 between 1987 and 1992, 4178 between 1992 and 1998, and 2631 between 1987 and 1998. Glucose tolerance was classified according to WHO 1999 criteria.Results.  The incidence rate of type 2 diabetes was higher between 1992 and 1998 than between 1987 and 1992. In men, the incidence was similar between cohorts (24.5 and 25.4 per 1000 person‐years) whereas the incidence increased in women (23.3 and 16.4 per 1000 person‐years). The incidence of diabetes peaked in the 45–54 year age group and then plateaud or fell. The incidences of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) decreased in both men and women. Of normoglycaemic subjects at baseline, more women than men developed IGT and more men than women developed IFG. Of those labelled as IFG in 1987, 38% developed diabetes after 11 years. The corresponding figure for IGT was 46%.Conclusions.  In this study, we report changes in incidence rates of glucose intolerance over a 11‐year period. In particular, differences between men and women were observed. The increased incidence of IGT in women compared with men, and increased incidence of IFG in men compared with women was consistent with, and explains the sex biases seen in the prevalences of these states.