bluuebunny/crossref_metadata_2025_split huggingface dataset:
A linkage between hereditary hyperferritinaemia not related to iron overload and autosomal dominant congenital cataract
Authors: GIRELLI DOMENTCO , OUVIERI OLIVIERO , FRANCESCHI LUCIA DE , CORROCHER ROBERTO , BERGAMASCHI GAETANO , CAZZOLA MARK 
Published: March 2008

Summary. The only genetic disorder with elevated serum ferritin levels so far described is hereditary HLA‐related haemochromatosis. On the other hand, hereditary cataract is both genotypically as well as phenotypically heterogenous, and no specific locus or any useful marker has been yet identified. We studied two Italian families in whom a combination of elevated serum ferritin not related to iron overload and congenital nuclear cataract is transmitted as an autosomal dominant trait. Affected individuals have normal serum iron and transferrin saturation, but high serum ferritin. Red cell counts are normal and venesection therapy rapidly produces iron‐deficiency anaemia.This genetic disorder, which is characterized by hyperferritinaemia, differs from hereditary HLA‐related haemochromatosis mostly for the absence of iron overload. A gene responsible for the congenital nuclear cataract likely maps on chromosome 19q close to the ferritin L‐subunit gene. Within families with autosomal dominant congenital cataract, serum ferritin might be an early marker of disease.
The prenatal identification of fetal compatibility in neonatal alloimmune thrombocytopenia using amniotic fluid and variable number of tandem repeat (VNTR) analysis
Authors: Denomme Gregory A. , Waye John S. , Borrows Robert F. , Hayward Catherine P. M. , Warkentin Theodore E. , Horsewood Peter , Smith James W. , Jelsema Russel D. , Zuidema Laura J. , Kelton John G. 
Published: March 2008

Summary. Most severe episodes of neonatal alloimmune thrombocytopenic purpura (NATP) are caused by antiplatelet alloantibodies against the HPA‐la (PlA1) antigen. However, half of subsequent fetuses produced from a HPA‐la/b father (genotypic frequency 28%) will result in a child who is not affected. Some investigators manage NATP by confirming the fetal platelet phenotype using percutaneous umbilical cord sampling, a procedure that carries a low but real risk of fetal morbidity and mortality. More recently, physicians determine the fetal platelet antigen genotype using DNA derived from amniotic fluid or chorionic villus samples. All therapy is withdrawn for a fetus who genotypes as HPA‐lb/b. However, since the fetus is the same genotype as the mother, there can be uncertainty about the origin of the genetic material and thus the validity of the fetal genotype. The inappropriate withdrawal of therapy for a erroneously genotyped fetus could be fatal, and consequently many physicians advocate fetal HPA‐1 phenotyping with confirmation using percutaneous umbilical blood sampling.In this report we describe the management of two pregnancies with previously affected infants due to anti‐HP A‐la alloantibodies. Both husbands were HPA‐la/b. For the current pregnancies, amniotic fluid was collected at 20 or 29 weeks of gestation, and the platelet genotype indicated that the fetuses were HPA‐lb/b. The fetal origin of the amniotic fluid derived DNA was confirmed by the forensic technique of DNA profiling using variable number of tandem repeat (VNTR) analysis. All therapy was withdrawn, percutaneous umbilical blood sampling was not performed, and both women vaginally delivered healthy non‐thrombocytopenic infants. The application of platelet alloantigen genotyping using DNA from amniotic fluid cells identified the HPA‐lb/b fetus, and VNTR analysis confirmed that the tissue was fetal derived, thus avoiding the necessity for percutaneous umbilical blood sampling. The use of this approach in patients at risk will avoid additional investigation and treatment in approximately one‐seventh of all NATP pregnancies involving the HPA‐la antigen.
Liver iron stores in patients with secondary haemosiderosis under iron chelation therapy with deferoxamine or deferiprone
Authors: Nielsen P. , Fischer R. , Engelhardt R. , Tondüry P. , Gabbe E. E. , Janka G. E. 
Published: March 2008

Summary. Total body iron stores including liver and spleen iron were assessed by non‐invasive SQUID biomagnetometry. The liver iron concentration was measured in groups of patients with β‐thalassaemia major or other post‐transfusional siderosis under treatment with the oral iron chelator deferiprone (n = 19) and/or with parenteral deferoxamine (n = 33). An interquartile range for liver iron concentrations of 1680‐4470μg/g liver was found in these patients. In both groups a poor correlation between liver iron and serum ferritin values was observed.Repeated measurements of liver and spleen iron concentrations as well as determination of liver and spleen volume by sonography were performed in six patients under continuous deferiprone treatment for 3‐15 months. In this group detailed information was obtained on the whole body iron store (5‐36 g) and the iron excretion rates (14‐34mg/d) for each patient. As indicated by decreasing liver iron concentrations, five out of six subjects showed a negative iron balance (2‐13 mg/d). Conventional measurements of both serum ferritin and urine iron excretion gave fluctuating results, thus being only of limited use in the control of iron depletion therapy.The non‐invasive biomagnetic liver iron quantification is a precise and clinically verified technique which offers more direct information on the long‐term efficacy of an iron depletion therapy than the hitherto used methods. This technique may be of use in the clinical evaluation of new oral iron chelators.
Effects of homo‐aza‐steroids on acute non‐lymphocytic leukaemia cell proliferation in vitro
Authors: Trafalis Dimitrios T. P. , Sambani Constantina , Kapsimali Violeta , Economidou Joanna , Politis George , Catsoulacos Panayotis 
Published: March 2008

Summary. Homo‐aza‐steroids (modified steroid molecules) in their esterified forms have been used extensively as carrier molecules of alkylating agents against several neoplastic malignancies in vivo and in vitro. We studied the effects of two homo‐aza‐steroid carrier molecules alone, namely 3β‐hydroxy‐13α‐amino‐13,17‐seco‐5α‐androstan‐17‐oic‐13, 17‐lactam (compound 1) and 13α‐amino‐13,17‐seco‐1,3,5‐estratrien‐17‐oic‐13,17‐lactam (compound 2), on human acute non‐lymphocytic leukaemia cell proliferation in vitro.We used peripheral blood samples from 27 untreated ANLL patients (eight M1, four M2, two M3, six M4, three M5a, two M5b and two M6, according to FAB criteria). Proliferative activity was estimated by using thymidine uptake and the percentage of cells in metaphase in 24, 48 and 72 h of culture. Exposure of human leukaemic blasts with either of the two compounds resulted in enhanced cell proliferation in M1, M2, M4, M6 and M5a (only by compound 2) cases, whereas there was no significant effect in the M3 and M5b cases.Our results indicate that the two compounds tested exhibit stimulatory effect on cell proliferation, particularly in blast cells possessing a relatively smaller degree of differentiation (Ml and M6 cases exhibiting CD34 and CD7). Further research is needed to study the cell growth effect and the therapeutic potential of these steroid molecules in human blood malignancies in vitro and in vivo.
A prospective study to determine the frequency and clinical significance of alloimmunization post‐transfusion
Authors: Heddle Nancy M. , Soutar Richard L. , O'Hoski Pamela L. , Singer Joel , McBride John A. , Ali Mohamed A. M. , Kelton John G. 
Published: March 2008

Summary. There is debate in the literature about the frequency and importance of delayed transfusion reactions. This uncertainty could reflect the endpoints used (clinical or serological) and the type of study (typically retrospective or case series). In this report we describe a prospective investigation to determine the frequency of alloimmunization post transfusion and whether the alloantibody production is a laboratory event or has clinical relevance.A total of 2490 patients were transfused 11218 red cell concentrates. One or more blood samples were collected within 7 d post transfusion and screened for serological evidence of alloimmunization. If any antibody was detected the patient's post‐transfusion sample was screened for biochemical evidence of haemolysis and the patient's chart reviewed for documentation of clinical signs of a transfusion reaction. Post transfusion alloimmunization occurred in 2.6% of the patients (95% CI 2.1–3.6%), who had no detectable alloantibody in pre‐transfusion testing. For those 86 patients (3.5%) with alloantibodies detectable pretransfusion, 8.9% (95% CI 3.6–17.4%) developed additional aloantibodies. The most common alloantibodies detected were anti‐Jka, anti‐E and anti‐K. Despite the high frequency of serological evidence of delayed transfusion reactions, only one patient (005%) had clinical evidence of a delayed haemolytic transfusion reaction (95% CI 0.0–0.27%). Serological evidence of a delayed transfusion reaction is common; however, these reactions rarely cause clinical symptoms.
Increased expression of the PRAD‐1/CCND1 gene in hairy cell leukaemia
Authors: Bosch Francesc , Campo Elias , Jares Pedro , Pittaluga Stefania , Muñoz Josep , Nayach Iracema , Piris Migdel Angel , Dewolf‐Peeters Chris , Jaffe Elaine S. , Rozman Ciril , Montserrat Emilio , Cardesa Antonio 
Published: March 2008

Summary. The PRAD‐1/CCND1 gene encodes Cyclin Dl, a cyclin involved in cell cycle regulation at the Gi‐S transition. Over‐expression of this gene is a highly specific molecular marker of mantle cell lymphomas (MCLs), but it may also be up‐regulated in some chronic lymphoprolifera‐tive disorders, mainly chronic lymphocytic leukaemia.We have examined PRAD‐1/CCND1 gene expression by Northern blot and Western blot analysis in a series of 18 hairy cell leukaemias (HCLs), nine other splenic malignant lymphoproliferative disorders, and three normal/reactive spleens. Over‐expression of the mRNA PRAD‐1/CCND1 gene was observed in 16/18 HCLs, including one case of hairy cell leukaemia variant, whereas this molecular alteration was not found in other cases examined. mRNA levels varied from case to case, but they were lower than those observed in MCLs. At the protein level, Western blotting analysis showed Cyclin D1 protein expression in the 11 HCLs analysed. No bcl‐1 rearrangements were seen with the MTC, p94PS and PRAD‐1 (Δ‐P1‐4) probes used, and no PRAD‐1/CCND1 gene amplification was detected in any case. These findings indicate that PRAD‐1/CCND1 is over‐expressed at mRNA and protein levels in a high number of HCLs. However, the levels of expression are much lower than in MCLs, and this expression is not associated with bcl‐1 rearrangements or PRAD‐1/CCND1 gene amplification.
Chronic active Epstein‐Barr virus disease in a case of persistent polyclonal B‐cell lymphocytosis
Authors: MITTERER MANFRED , PESCOSTA NORBERT , FEND FALKO , LARCHER CLARA , PRANG NADJA , SCHWARZMANN FRITZ , COSER PAOLO , HUEMER HARTWIG P. 
Published: March 2008

Summary. Persistent polyclonal B‐cell lymphocytosis (PPBL) is a rare haematological disorder. It is characterized by activated and morphologically atypical B lymphocytes and polyclonal IgM production and has been associated with female sex, cigarette smoking, and HLA‐DR7 expression.We report a case of PPBL with intermitting symptoms compatible with a chronic fatigue syndrome, recurrent erythema nodosum and multiforme. Serological findings suggested a chronic active Epstein‐Barr virus (EBV) infection. Messenger RNA of EBV immediate early gene transactivation BZLF1 was detected in peripheral blood lymphocytes by reverse transcriptase PCR indicating a persistent replication of the virus. Over 2 years of observation we detected varying numbers of atypical lymphocytes. These cells hybridized with a probe specific for the EBV internal repeat region (BamHI W) which indicates a productive infection. Of interest, no reaction was observed with a probe specific for the latency‐associated small RNAs (EBERs). The immunological phenotype of the polyclonal B cells was similar to B‐cell lines immortalized by EBV in vitro, expressing a number of activation molecules (CD23, CD25, CD54) and the bcl‐2 protein. In summary, our findings suggest that persistent EBV replication might be crucial in the development of lymphoproliferative disorders such as PPBL.
Ethnic distribution of allele aLELY, a low‐expression allele of red‐cell spectrin a‐gene
Authors: MARECHAL J. , WILMOTTE R. , KANZAKI A. , DHERMY D. , GARBARZ M. , GALAND C. , TANG T. K. , YAWATA Y. , DELAONAY J. 
Published: March 2008

Summary. AlleleαLELY	low‐expression allele of erythroid spectrin a‐chain. It carries mutations both in exon 40 and intron 45 and is associated with partial skipping of exon 46. Allele αLELY remains asymptomatic by itself. In contrast, it enhances the expression level of deleterious α‐alleles occurring in trans, and as such has clinical importance. The aim of this study was to evaluate the incidence of allele QLBLY mvarjous ethnic groups, i.e. Caucasians, African Blacks, Japanese and Chinese. Allele QLELY occurred in all groups investigated with a fairly uniform frequency: 31%, 21%, 20% and 22%, respectively. Mutations in exon 40 and intron 45 appeared linked to one another without exception. Partial skipping of exon 46 or the low‐expression feature, whenever they could be assessed, were invariably observed. Allele αLELY appears to be an ancient and stable allele.
The myelodysplastic syndromes: an analysis of prognostic factors in 226 cases from a single institution
Authors: CUNNINGHAM I. , MACCALLUM S. J. , NICHOLLS M. D. , BYTH K. , HEWSON J. W. , ARNOLD B. , MOTUM P. I. , MULLIGAN S. P. , CRANE G. G. 
Published: March 2008

Summary. Two hundred and twenty‐six patients were diagnosed with myelodysplastic syndrome (MDS), according to the French‐American‐British (FAB) criteria, over a 13‐year period, and studied retrospectively in a single institution in order to study indicators which were prognostically significant.Analysis of clinical and laboratory data indicated that the FAB classification, the Bournemouth, Dusseldorf, Goasguen, Sanz and FAB Scoring Systems were all good predictors of survival.We found advancing age, haemoglobin (Hb) ≤ 9g/dl, platelet count ≤ 50 × 109/1, increased peripheral total white cell count (WCC) and monocytosis, increased bone marrow blasts, dysgranulopoiesis, and bone marrow fibrosis were significant adverse prognostic variables.The commonest complication and cause of death was infection; however, infective episodes were not significantly associated with low neutrophil counts (either ≤ 1‐5 × 109/1 or ≤ 08 × 109/1) and there was also no significant association between neutropenia and survival. These findings indicate that neutrophil dysfunction plays an important role in the clinical progression of patients with MDS. The effect of new therapeutic modalities, such as the haemopoietic growth factors, on reducing infective episodes may be as significant as their effect on increasing neutrophil counts.
CD3‐induced T‐cell activation in the bone marrow of myeloma patients: major role of CD4+ cells
Authors: BIANCHI ALBERTO , MONTACCHINI LAURA , BARRAL PAOLA , BORRIONE PAOLO , ATTLSANO CARMELA , ORSINI ENRICA , BOCCADORO MARIO , PILERI ALESSANDRO , MASSAIA MASSIMO 
Published: March 2008

Summary. A large expansion of activated T cells (CD3+CD25+) with the potential to act as anti‐tumour effector cells is inducible in multiple myeloma (MM) patients by culturing bone marrow mononuclear cells (BMMCs) with the anti‐CD3 monoclonal antibody (mAb) OKT3. The aim of this study was to provide a greater characterization of CD3‐activated T cells. On day 6, most T cells coexpressed the CD1 la, CD18, CD54, CD45R0 antigens and consisted of activated (CD25+) CD4+ and CD8+ cells in nearly equal proportions. Kinetics studies showed that CD4+CD25+ cells proliferated more rapidly and peaked earlier than CD8+CD25+ cells. When experiments were performed with purified subpopulations by removing CD4+ cells (resulting in CD8+ BMMCs) or by removing CD8+ cells (resulting in CD4+ BMMCs), T‐cell activation and autologous plasma cell decrease were observed in CD4+ BMMCs only. Transwell cultures showed that CD4 help was necessary to make CD8+ BMMCs susceptible to CD3 stimulation. Relevant amounts of IL‐2 were found in the supernatants of CD4+ BMMCs cultures, whereas no secretion of IL‐4 was detected, indicating a Thl‐like profile of CD3‐activated CD4+ cells.These data indicate that CD4+ cells proliferate earlier and provide optimal help to induce the subsequent expansion of CD8+ cells after CD3 stimulation of MM BMMCs. Adequate stimulation of CD4+ cells is therefore essential in any strategy aiming to recover T‐cell‐mediated immunity in MM.
Fatal haemoptysis in pulmonary filamentous mycosis: an underevaluated cause of death in patients with acute leukaemia in haematological complete remission. A retrospective study and review of the literature
Authors: PAGANO LIVIO , Ricci Paolo , Nosari Annamaria , Tonso Anna , Buelli Massimo , Montillo Marco , Cudillo Laura , Cenacchi Annarita , Savignana Chiara , Melillo Lorella , Chierichini Anna , Marra Roberto , Bucaneve Giampaolo , Leone Giuseppe , Favero Albano Del ,   The Gimema Infection Program(Gruppo Italiano Malattie Ematologiche dell'Adulto)
Published: March 2008

A retrospective study on a consecutive series of 116 patients affected by acute leukaemia with documented pulmonary filamentous mycosis (FM) admitted between 1987 and 1992 to 14 tertiary‐care hospitals in Italy was made in order to evaluate the characteristics of those patients who developed fatal massive haemoptysis.In 59/116 cases of pulmonary FM the infection was the principal cause of death and in 12 of these patients a massive haemoptysis was responsible for death. The diagnosis of FM infection was made ante‐mortem in only four out of these 12 patients. The autopsy was performed in 11/12 patients and documented a FM infection. The mycetes isolated were: Hyphomycetes spp. (three patients), Mucorales spp. (two patients), Aspergillus spp. (seven patients).At the time of the massive haemoptysis the mean neutrophil count was 7.2x109/1, and no patient had relevant thrombocytopenia (mean 184x109/1, range 28‐350) or coagulative abnormalities. The mean time which elapsed between resolution of chemotherapy‐induced neutropenia (WBC <109/1) and occurrence of haemoptysis was 7 d. No signs or symptoms predictive of this fatal complication were identified.Massive haemoptysis can be the cause of death in patients with acute leukaemia and pulmonary FM which in the majority of patients was not diagnosed in vivo. This complication occurs most frequently shortly after the recovery from chemotherapy‐induced aplasia. The mechanism of lesion is unknown, but it may involve the vascular tropism of FM and the release of leucocyte enzymes. Better preventive and therapeutic antifungal treatments are needed to avoid this serious, albeit rare, complication.
Heterogeneity of t(1;19)(q23;p13) acute leukaemias
Authors: Troussard Xavier , Rimokh Ruth , Valensi Francoise , Leboeuf Daniel , Fennbtbau Odile , Guitard Anne‐Marie , Manel Anne‐Marie , Schillinger Franćloise , Leglise Chantal , Brizard André , Gardais Jacques , Lessard Michel , Flandrin Georges , Macintyre Elizabeth ,   For the French Haematological Cytology Group
Published: March 2008

The t(1; 19)(q23;p13) translocation occurs commonly in B‐lineage ALL. Previous reports have demonstrated a predominance of cases with expression of cytoplasmic Igμ (Cμ+), an FAB L1/L2 phenotype, a poor prognosis and expression of a fusion transcript involving the E2A and PBX1 genes in Cμ+ but not in Cμ‐ cases.Of 38 patients with karyotypically proven t(1;19) (q23;p13) leukaemias, we extensively analysed 18 patients with acute leukaemia including 16 B‐lineage ALLs, one T‐ALL and one AML M4. The AML was associated with a classic E2A‐PBX1 fusion transcript and may represent the human counterpart of the AMLs induced by E2A‐PBX1 retroviral infection of murine marrow progenitors. The T‐ALL was E2A‐PBX1 negative and neither the E2A nor the LYL‐1 genes, both situated at chromosome 19 p13, were rearranged. Of the 16 B‐lineage ALLs, four had cytological features resembling an ‘L3‐like’phenotype classically associated with Burkitt's lymphoma, two at diagnosis and relapse and two exclusively at relapse. E2A‐PBX1 fusion transcripts were detected by RT‐PCR in all 13 Cμ+ patients and in 2/3 Cμ‐ cases. The ‘L3‐like’phenotype did not correlate with a particular stage of maturation arrest (one sIg+, one Cμ+, one Cμ‐) or type of E2A‐PBX1 transcript, but was associated in all cases with a trisomy 8. Translocation, rearrangement, amplification or over‐expression of the c‐myc gene was not observed in these cases, demonstrating that the apparent association with trisomy 8 is not due to deregulation of this gene.We therefore show that the E2A‐PBX1 transcript. although occurring predominantly in Cμ+ pre‐B ALL, also occurs in Cμ‐ early pre‐B ALL, sIg+ B‐ALL and even in AML. These results suggest that the stage of maturation arrest, and indirectly the prognosis, are not soiely due to the type of fusion transcript associated with the t(1;19).
Interferon alfa‐2b versus no maintenance therapy during the plateau phase in multiple myeloma: a randomized study
Authors: Westin Jan , Rödjer Stig , Turesson Ingemar , Cortelezzi Agostino , Hjorth Martin , Zador Göran ,   for a Cooperative Study Group
Published: March 2008

This clinical trial was designed to investigate if maintenance therapy with alfa‐interferon could prolong the plateau phase in patients with multiple myeloma. In addition, the tolerability of interferon treatment and its effect on survival were evaluated.From September 1987 to September 1989 a total of 314 patients were accrued to a multi‐institutional randomized clinical trial. All patients entered into the protocol received standard melphalan‐prednisone (MP) induction therapy. Response was noted in 184 (59%) and a plateau phase achieved in 155 (49%). From the latter group, 125 eligible patients were randomized to either interferon alfa‐2b or no maintenance. The patients were followed for an average of 51 months (minimum 36 months) from the time of randomization.The plateau phase was significantly prolonged in the group of patients treated with interferon (median 13.9 v 5.7 months from the time of randomization;P< 0.0001). The interferon therapy was tolerated fairly well, moderate granulocytopenia and a chronic fatigue syndrome being the most frequent side‐effects (22% v 18% W.H.O. grade 3 toxicity). The median survival from randomization was almost identical in both groups (36 v 35 months).The study shows that interferon maintenance therapy given to multiple myeloma patients who have achieved a response to initial treatment with MP prolongs the plateau phase duration with tolerable toxicity. The clinical value of this finding should be interpreted with caution, because survival was not prolonged. Further studies are required to clarify the role of interferon in the treatment of multiple myeloma.