bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential constitutive activation between STAT‐related proteins and MAP kinase in primary acute myelogenous leukaemia
Authors: Hayakawa Fumihiko , Towatari Masayuki , Iida Hiroatsu , Wakao Hiroshi , Kiyoi Hitoshi , Naoe Tomoki , Saito Hidehiko 
Published: March 2003

Many cytokines and growth factors stimulate multiple signal transduction pathways essential for proliferation in human acute leukaemia cells, including a mitogen‐activated protein (MAP) kinase pathway and a Janus kinase (JAK)‐STAT (signal transducers and activators of transcription) pathway. We have previously shown constitutive activation of MAP kinase in approximately 50% of acute myelogenous leukaemia (AML) samples. Recently, STAT proteins have been reported to be constitutively activated in 10–20% of AML cases. STAT3 and STAT5 are the main STAT proteins activated in haemopoietic progenitors in response to cytokines such as IL‐3, GM‐CSF, erythropoietin and thrombopoietin. Although the possibility of STAT1 protein as a substrate for MAP kinase at a serine residue has been suggested, the cross‐talk between STATs and MAP kinase pathways in vivo, especially in leukaemia cells, remains unknown.We examined the phosphorylation of STAT3 and STAT5 at the tyrosine residues in AML samples in which MAP kinase activity had already been found. 40/50 primary AML cases (80%) exhibited constitutive tyrosine phosphorylation of STAT5. Electrophoretic mobility shift assay showed DNA binding activity of STAT5 correlated with tyrosine phosphorylation of STAT5. Similarly, with respect to STAT3, 17/23 cases examined (74%) showed constitutive tyrosine phosphorylation of STAT3. In addition, we examined the tyrosyl‐phosphorylation of STAT5 isoforms, STAT5A and STAT5B, in 20 AML cases, and found selective STAT5B phosphorylation in the absence of STAT5A phosphorylation in three cases. Furthermore, in certain AML cases, constitutive activation of MAP kinase and STAT proteins occurred independently. No significant correlation of MAP kinase activation was observed with either tyrosine phosphorylation of STAT3/STAT5 or positive DNA binding of STAT proteins. These results suggest that constitutive activation of STAT proteins occurs commonly and that the causes of constitutive activation of these two major cascades are heterogenous in AML.
Genomic typing of the Kidd blood group locus by a single‐tube allele‐specific primer PCR technique
Authors: Irshaid Nidal M. , Thuresson Britt , Olsson Martin L. 
Published: March 2003

The Kidd (JK) blood group system is clinically important in transfusion medicine. Alloantibodies to antigens in this system may be produced following blood transfusion or during pregnancy and can result in serious haemolytic transfusion reactions and haemolytic disease of the newborn (HDN).JK antigens on erythrocytes are carried by glycoproteins with the capacity to transport urea through cell membranes. cDNA complementary to mRNA transcribed at the JK locus was cloned in 1994. The molecular basis of the Jka/Jkb blood group polymorphism was recently shown to be a single nucleotide substitution predicting an amino acid change (Asp280Asn) in an extracellular loop of the JK glycoprotein.After confirmation of the JK gene polymorphism we developed a rapid and robust technique for JK genotyping with allele‐specific primers in a single‐tube PCR. In addition, a 217 bp intron located at nucleotides 811–812 in the JK gene was found and sequenced. The genotyping test was validated with samples from 106 Caucasian Swedish and 13 Black South African random blood donors. Complete phenotype–genotype correlations were obtained. However, four Jk(a−b−) samples of Polynesian and Finnish origin typed as JkbJkb.Potential use of the presented method can be predicted in clinical transfusion medicine including prenatal determination of the JK genotype in a fetus at risk for HDN caused by JK antibodies.
Detection of weak D and DVI red cells in D‐negative mixtures by flow cytometry: implications for feto‐maternal haemorrhage quantification and D typing policies for newborns
Authors: LLOYD‐EVANS P. , GUEST A. R. , VOAK D. , SCOTT M. L. 
Published: March 2003

Quantitation of feto‐maternal haemorrhage (FMH) by flow cytometry (FC) has been shown to be more accurate than the Kleihauer‐Bekte test. Fetal cells will be predominately of R1r or R2r phenotype, with antigen site numbers per cell (SPC) of between 9900 and 16 000. If the fetus is of weak D or partial DVI phenotype, fewer SPC will be present.Red cells from 20 adult weak D samples were mixed with rr red cells to give 1% mixes. Mixtures were stained and analysed by FC, using two different monoclonal reagents. The SPC of each sample was measured using SOL‐ELISA with Scatchard plot analysis. 18 samples could not be distinguished and had <1000 SPC. Two samples that could be distinguished had 1350 and 3000 SPC.Red cells from seven samples of DVI were also analysed. None of these samples could be distinguished; SPC were all <1000. Although one of the reagents used reacts with DVI cells, quantitation of a DVI FMH would not be possible due to low SPC.The ability of fetal red cells with low Rh D SPC to cause immunization is questionable; failure to measure FMH in these cases is unlikely to cause clinical problems, as long as suitably sensitive serological reagents and techniques are used to type all weak D and D variant babies as Rh D positive, and thus ensure that the mother is given the appropriate dose of anti‐D.
A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies
Authors: Morgenstern Godfrey R. , Prentice Archibald G. , Grant Prentice H. , Ropner Janet E. , Schey Stephen A. , Warnock David W. ,   on behalf of the U.K. Multicentre Antifungal Prophylaxis Study Group
Published: March 2003

Fluconazole is widely used as antifungal prophylaxis but it is ineffective against Aspergillus. Itraconazole has a broader spectrum of activity but the capsules give erratic bioavailability in neutropenic patients. We compared itraconazole oral solution (which has an improved pharmacokinetic profile) with fluconazole for antifungal prophylaxis.Adults with haematological malignancies receiving chemotherapy or bone marrow transplants were randomly allocated 5 mg/kg/d itraconazole (itra) solution (288 episodes) or 100 mg fluconazole suspension (flu) (293 episodes) from before the onset of neutropenia until neutrophil recovery or suspected fungal infection. Outcomes were assessed by independent reviewers unaware of the prophylaxis allocation.More proven systemic fungal infections occurred in flu (Aspergillus four, Candida tropicalis one, C. krusei one) than itra (C. albicans one) and more of these were fatal (four versus nil). This difference reached statistical significance when first study episodes were considered separately (six flu versus nil itra, P = 0.03). Significantly more deaths of presumed fungal origin occurred in flu than itra (seven versus nil, P = 0.024). There were significantly more cases of proven aspergillosis in flu than itra (six versus nil, P = 0.038, 5/6 cases were fatal) if those occurring outside the study period are included. Significantly more patients receiving flu required amphotericin B (58 v 39, P = 0.043) but this may have been affected by the fact that the study was not blinded. There were 11 proven mucosal candidal infections in flu and four in itra.Itraconazole solution and fluconazole provide effective prophylaxis against Candida but itraconazole affords greater protection against fatal aspergillosis.
Human osteoclasts derive from CD14‐positive monocytes
Authors: Massey  , Flanagan  
Published: March 2003

Osteoclasts have been defined as calcitonin (CT) and vitronectin (VN) receptor (R) positive, and CD14‐, CD11b‐ and CD11c‐negative cells which resorb bone. The aim of this study was to identify the phenotype of the osteoclast precursor. Osteoclasts were generated by co‐culturing peripheral blood mononuclear cells (PBMNCS) with the rat osteoblastic UMR 106 cell line. On days 2–4 at least 80% of CTR‐positive cells co‐expressed CD14, CD11b and CD11c (monocyte markers), but by day 14 < 3.3% expressed these markers. Selection of CD14‐positive monocytes from PBMNCS enhanced osteoclastic bone resorption 2–4‐fold compared to unfractionated PBMNCS.This study demonstrates that osteoclasts derive largely from CD14‐positive monocytes.
Defective functional activity and accelerated apoptosis in neutrophils from children with cancer are differentially corrected by granulocyte and granulocyte‐macrophage colony stimulating factors in vitro
Authors: Lejeune Marylène , Cantinieaux Brigitte , Harag Saadia , Ferster Alina , Devalck Christine , Sariban Eric 
Published: March 2003

We have previously shown that polymorphonuclear leucocytes (PMN) harvested from children with cancer and exposed to chemotherapy exhibit defective bactericidal activities against both Gram‐positive and Gram‐negative microorganisms as well as accelerated apoptosis. In this study, PMN from children with cancer were evaluated to compare in vitro the corrective effects of the two myeloid colony stimulating factors G‐CSF and GM‐CSF on these defective pathways. Both G‐CSF and GM‐CSF were able to increase the defective bactericidal activities against S. aureus and E. coli. However, GM‐CSF was consistently superior to G‐CSF in correcting PMN microbicidal activity; this correction was incomplete since it did not reach the level observed in normal PMN exposed to GM‐CSF.The accelerated apoptosis of PMN was not affected by G‐CSF. In contrast, GM‐CSF significantly prolonged the survival of the PMN although it did not reach the level of survival observed with normal PMN exposed to GM‐CSF.These observations were consistent with other studies indicating that in PMN, microbicidal activities and apoptosis are differentially sensitive to the myeloid growth factors G‐CSF and GM‐CSF.
Essential role for T cells in human B‐cell lymphoproliferative disease development in severe combined immunodeficient mice
Authors: Johannessen I. , Asghar M. , Crawford D. H. 
Published: March 2003

Epstein–Barr virus (EBV)‐positive B‐cell lymphoproliferative disease (BLPD)‐like lesions develop in severe combined immunodeficient (SCID) mice inoculated with peripheral blood mononuclear cells (PBMCs) from EBV‐seropositive donors. We used this model to investigate the pathogenesis of EBV‐associated BLPD. Tumour incidence fell from 81% to 11% when only B cells were inoculated, suggesting a key role for T cells in tumour formation. This was further underlined by the reduction in tumour incidence from 76% to 7% when PBMCs were depleted of CD4 positive (+ve) helper T cells. Tumour outgrowth was also reduced when PBMC were depleted of CD8 +ve, CD45RA +ve or CD45RO +ve T cells. The majority of PBMC‐derived tumours analysed by reverse transcriptase–polymerase chain reaction (RT–PCR) expressed mRNA for interleukin (IL) 2, 4, 6, 10 and interferon (IFN) γ. This is the cytokine pattern seen in activated T cells and includes B‐cell growth factors. In situ hybridization studies confirmed that the tumour cells themselves express the growth factors, which is consistent with autocrine‐stimulated tumour growth.Our results suggest the following sequence of events: (1) T cells are essential for the initial outgrowth of tumorigenic EBV +ve B cells in vivo; (2) the neoplasm sustains its growth in an autocrine, cytokine‐stimulated manner; and (3) established tumours become independent of T‐cell help.
Detection of diagnostically critical, often hidden, anomalies in complex karyotypes of haematological disorders using multicolour fluorescence in situ hybridization
Authors: Jalal S. M. , Law M. E. , Stamberg J. , Fonseca R. , Seely J. R. , Myers W. H. , Hanson C. A. 
Published: March 2003

Multicolour fluorescence in situ hybridization (M‐FISH) simultaneously detects all 24 human chromosomes in unique fluorescent colours. The identification of diagnostically critical gene rearrangement(s) in complex karyotypes of haematological disorders continues to be a challenge. We present five cases in which t(9;11), complex t(8;22), t(12;21) and t(11;14) were detected primarily using M‐FISH and were confirmed using locus‐specific probes. We conclude that M‐FISH can be effective in complete characterization of critical gene rearrangements in haematological disorders.
Two further British families with the ‘cryohydrocytosis’ form of hereditary stomatocytosis
Authors: Haines Philip G. , Jarvis Helen G. , King Simon , Noormohamed Faruq H. , Chetty Margaret C. , Fisher Julie , Hill P. , Nicolaou Anna , Stewart Gordon W. 
Published: March 2003

We describe two families with the ‘cryohydrocytosis’ form of stomatocytosis. Both show a mild stomatocytic anaemia with Hb levels of 12–16 g/dl and reticulocyte counts of 4·3–24%, with very marked autohaemolysis at refrigerator temperatures and pseudohyperkalaemia as a result of loss of K from red cells on storage at room temperature. The ouabain + bumetanide‐insensitive ‘passive leak’ K influx showed a ‘U’‐shaped temperature dependence, with a minimum at 23°C. In one family, there was consistent variation in haematological severity within the pedigree. In the other, the parents of the proposita were normal, but all three of her children were affected, consistent with a new mutation of a dominant condition. Cold storage of the red cells led to a very marked increase in osmotic fragility and macrospherocytosis, explaining why a diagnosis of ‘hereditary spherocytosis’ can easily be reached in these pedigrees.
Identification of both myeloid CD11c+ and lymphoid CD11c− dendritic cell subsets in cord blood
Authors: Borràs Francesc E. , Matthews Nick C. , Lowdell Mark W. , Navarrete Cristina V. 
Published: March 2003

Dendritic cells (DCs) are the most potent antigen‐presenting cells described to date. In human peripheral blood, both myeloid and lymphoid subsets of DCs have been identified. In contrast, cord blood (CB) DCs have recently been described as being exclusively of the immature CD11c− lymphoid DC subset. Using an alternative method of enrichment, based on a negative selection system, both lymphoid (HLA‐DR+ CD123+++ CD11c− CD33−) and myeloid (HLA‐DR++ CD123+ CD11c+ CD33+) DCs were identified in CB. Although the majority of CB DCs showed a lymphoid phenotype, a significant number of CD11c+ myeloid DCs (25·6% ± 14·5%, n = 13) were also present. Other markers, such as CD80 and CD83, were negative in both subsets. Analyses of the allostimulatory capacity of both subsets showed that freshly isolated CB lymphoid DCs failed to induce a potent allostimulation of naive CB T cells. These features are therefore consistent with previous work reporting an immature phenotype for lymphoid DCs in adult blood. The significance of the inverted CD11c+/CD11c− ratio observed in CB DCs (1:3) with respect to adult blood DCs (3:1) remains to be explained.
Dose‐reduced conditioning for allografting in 44 patients with chronic myeloid leukaemia: a retrospective analysis
Authors: Bornhäuser Martin , Kiehl Michael , Siegert Wolfgang , Schetelig Johannes , Hertenstein Bernd , Martin Hans , Schwerdtfeger Rainer , Sayer Herbert G. , Runde Volker , Kröger Nikolaus , Theuser Catrin , Ehninger Gerhard ,   the Cooperative German Transplant Study Group
Published: March 2003

This retrospective study describes the outcome of patients with chronic myeloid leukaemia after allografting using dose‐reduced conditioning with fludarabine and busulphan. Forty‐four Philadelphia chromosome (Ph)‐positive patients were transplanted in nine German centres; 26 patients were in chronic phase, 11 in accelerated phase and seven in blast crisis. Thirty‐four patients achieved complete remission, with 18 alive and disease‐free at a median follow‐up of 562 d (range 244–922 d). Grade II–IV acute graft‐versus‐host disease (GVHD) incidence was 43%. Twenty patients died, 15 of causes unrelated to relapse. Risk factors predisposing to graft failure by univariate analysis were an unrelated donor (8/23 compared with a related donor 2/21, P = 0·07) and interferon therapy within 90 d of transplant (4/6 versus 3/17, P = 0·025). At the last follow‐up, of 31 patients for whom molecular or cytogenetic data were available, 16 (52%) were polymerase chain reaction‐negative, and seven (23%) were Ph‐negative by fluorescent in situ hybridization. These findings demonstrate that dose‐reduced conditioning with fludarabine and busulphan provides durable engraftment and a low rate of relapse. However, in this population, many of whom were not eligible for high‐dose conditioning due to age, reduced performance status, previous complications or extensive pre‐treatment, these data highlight the need for effective anti‐infectious and GVHD prophylaxis. In addition, this study supports the discontinuation of interferon therapy at least 90 d before transplant
Abdominal infections in patients with acute leukaemia: a prospective study applying ultrasonography and microbiology
Authors: Gorschlüter Marcus , Marklein Günter , Höfling Katja , Clarenbach Ricarda , Baumgartner Stefanie , Hahn Corinna , Ziske Carsten , Mey Ulrich , Heller Ricarda , Eis‐Hübinger Anna Maria , Sauerbruch Tilman , Schmidt‐Wolf Ingo G. H. , Glasmacher Axel 
Published: March 2003

Summary.  A prospective study of 62 chemotherapy‐	induced neutropenic episodes in patients with acute leukaemia was conducted to determine the incidence and causes of abdominal infections, and to assess the diagnostic value of the combined use of ultrasonography (US) and microbiology. Each patient underwent US of liver, gallbladder and complete bowel before chemotherapy, on days 2–4 after the end of chemotherapy and in cases of fever, diarrhoea or abdominal pain. US was combined with a standardized clinical examination and a broad spectrum of microbiological investigations. From January to August 2001, 243 US examinations were performed. The overall incidence of abdominal infectious diseases was 17·7% (11 out of 62, 95% confidence interval (CI): 9–29%). Four patients (6·5%) developed neutropenic enterocolitis; two of them died, two survived. Bowel wall thickening (BWT) > 4 mm in these four patients ranged from 5·8 to 23·6 mm and was detected only in one patient with mucositis. In three other patients (4·8%) Clostridium difficile, and in one patient (1·6%) Campylobacter jejuni, caused enterocolitis without BWT. Cholecystitis was diagnosed in three patients (4·8%) and hepatic candidiasis was strongly suspected in one patient. Abdominal infections caused by gastroenteritis viruses, cytomegalovirus (CMV) or Cryptosporidium were not observed. We conclude that in neutropenic patients with acute leukaemia receiving chemotherapy: (i) BWT is not a feature of chemotherapy‐induced mucositis and should therefore be considered as sign of infectious enterocolitis; (ii) viruses, classic bacterial enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Aeromonas, Vibrio subsp., enterohaemorrhagic Escherichia coli) and Cryptosporidium have a very low incidence; and (iii) abdominal infections may be underestimated when US is not used in every patient with abdominal pain.
Continued change in the distribution of colorectal carcinoma
Authors: Obrand D I , Gordon P H 
Published: March 2003

Abstract

Background
The aim of this study was to determine whether the previously reported shift in carcinoma from the left colon to the right colon has progressed.

Methods
The charts of 2169 patients admitted to one institution between 1979 and 1994 with a diagnosis of colorectal carcinoma were reviewed retrospectively. The study was divided into four equal intervals. The large bowel was divided into five regions: right, transverse, left, sigmoid and rectum.

Results
Right-sided lesions increased from 20·6 to 29·9 per cent (P = 0·001) and rectal lesions decreased from 22·0 to 11·3 per cent (P = 0·0002) from the first to the fourth study interval. The frequency of transverse, left and sigmoid colon lesions remained relatively constant.

Conclusion
The continuing trend of increased incidence of right-sided lesions and decreased incidence of rectal lesions was documented. Any screening examination for carcinoma requires total examination of the colon.
International differences in survival from colon cancer: more effective care versus less complete cancer registration
Authors: Prior P , Woodman C B J , Collins S 
Published: March 2003

Abstract

Background
Reporting of a recent international comparison of cancer survival rates has left an impression of inadequate treatment of patients in the UK but failed to address adequately the extent to which differences in survival may reflect variation in the completeness and accuracy of cancer registration. The aim of this study was to quantify the extent to which differences in registration practice may confound comparisons of survival from cancer of the colon.

Methods
A cohort of incident cases of colon cancer identified from records held by the North Western Regional Cancer Registry was used to simulate the effects on survival of changes in clinical and registration factors. The survival curve produced after each simulation was compared with that for aggregated data from 21 European registries.

Results
The observed survival differences were not explained by more effective primary treatment or by misclassification of in situ cases as malignant disease, whereas the exclusion of cases with only a clinical diagnosis produced estimates close to those of the European cohort.

Conclusion
The observed survival differentials may not be due to differences in the quality of care but may reflect the failure of some European registries to register all patients with advanced disease.
Temporary decompression after colorectal surgery: randomized comparison of loop ileostomy and loop colostomy
Authors: Gooszen A W , Geelkerken R H , Hermans J , Lagaay M B , Gooszen H G 
Published: March 2003

Abstract

Background
Loop ileostomy or loop transverse colostomy for temporary decompression of a left colonic anastomosis represents an important issue in abdominal surgery.

Methods
A randomized study, comparing loop ileostomy (n = 37; group 1) or loop transverse colostomy (n = 39; group 2), was conducted. Patients were followed from construction to closure of the stoma.

Results
Age, weight, sex and indication for surgery were similar in both groups. After stoma construction complications were reported in nine of 37 patients in group 1 and in one of 39 in group 2 (P &lt; 0·01), leading to postoperative death in five of 37 in group 1 and one of 39 in group 2. In the period between stoma construction and closure significant differences were observed only in prolapse rate (one of 32 group 1, 16 of 38 group 2; P &lt; 0·01), need for temporary adaptation of clothing (eight of 32 group 1, 22 of 38 group 2; P &lt; 0·01) and dietary guidelines (23 of 32 group 1, four of 38 group 2; P &lt; 0·01). One patient died in group 1 and four in group 2; the deaths were not stoma related. After stoma closure eight of 29 patients in group 1 had complications and there were two deaths compared with three of 32 and no deaths in group 2.

Conclusion
Both types of stoma carry a high complication rate with a considerable associated mortality rate. The interval between stoma construction and closure has substantial impact on social and economic status. Based on all three phases studied, routine use of transverse colostomy is advised if decompression of the left colon is indicated.