bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoglobulin heavy chain Diversity genes rearrangement pattern indicates that MALT‐type gastric lymphoma B cells have undergone an antigen selection process
Authors: Bertoni Francesco , Cazzaniga Giovanni , Bosshard Giovanna , Roggero Enrico , Barbazza Renzo , De Boni Michele , Capella Carlo , Pedrinis Ennio , Cavalli Franco , Biondi Andrea , Zucca Emanuele 
Published: November 2003

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement.DNA was extracted from paraffin‐embedded sections and the rearranged CDR3 regions were amplified using a semi‐nested polymerase chain reaction (with primers complementary to the conserved framework‐three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N‐D‐N region specific to each clone was compared with known germline D sequences.Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B‐cell clones appeared to contain two D gene segments (D‐D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen‐binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen.The observed pattern of D gene rearrangement suggests that MALT lymphoma B‐cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.
Microsatellite instability and other molecular abnormalities in childhood acute lymphoblastic leukaemia
Authors: Takeuchi Seisho , Seriu Taku , Tasaka Taizo , Koike Michiaki , Cho Steve K. , Park Susan , Slater James , Mufti Iqbal , Hatta Yoshihiro , Miyoshi Isao , Bartram Claus R. , Koeffler H. Phillip 
Published: November 2003

Microsatellite instability (MSI) has been considered to represent the defect of DNA mismatch repair systems and has been implicated in the tumourigenesis of several human malignancies. To investigate the possible presence of microsatellite instability in childhood acute lymphoblastic leukaemia (ALL), we examined 48 primary ALL samples. Instability was determined at 85 different microsatellite loci localized to 12 different chromosome arms.  Microsatellite instability was detected in five (10%) samples. Interestingly, the instability was found at chromosomal regions associated with frequent alterations. Two samples had instability at the microsatellite marker within the TEL gene on chromosome arm 12p. Two other samples had instability at a microsatellite marker close to CDKN2/p16 on 9p; one of these samples had a homozygous deletion at 9p21. The fifth sample had instability at the microsatellite marker on 6q, which we have found is a frequent region of loss of heterozygosity in childhood ALL.Taken together, instability was rare in childhood ALL, but was localized to the three most frequently deleted chromosome regions in childhood ALL, suggesting that localized microsatellite instability may identify a fragile chromosomal region which could result in alteration of surrounding target genes and lead to leukaemia.
Immunophenotypic and ultrastructural study in peripheral blood neutrophil granulocytes following bone marrow transplantation
Authors: MASAT T. , FELIU E. , VILLAMOR N. , CASTELLSAGUÉ J. , ORDI J. , FABREGUES M. , ROZMAN C. 
Published: November 2003

Neutrophil studies after bone marrow transplantation (BMT) describe chemotactic and phagocytotic alterations and dyshaemopoiesis. Neutrophil granulocytes (NG) in peripheral blood after BMT were analysed in 28 patients. 14 patients (six receiving GM‐CSF) underwent autologous BMT and 14 underwent allogeneic BMT. Immunophenotypic and electron microscopic studies were performed during post‐BMT granulopoietic regeneration. Results were compared with NG from 15 healthy bone marrow donors (control group A) and from six patients receiving intensive chemotherapy before autologous BMT (control group B).A significant increase in CD15 and a decrease in 8C7 antigen expression was observed in peripheral blood NG from BMT patients compared with controls A. MPO‐7 in NG after BMT did not differ from control group A. Autologous BMT patients showed a lower percentage of NG expressing 13F6, 31D8 and CD16 (Leu 11a) than allogeneic BMT patients, and a significant decrease in 8C7 antigen expression compared with patients receiving intensive chemotherapy. Ultrastructurally, a marked decrease of azurophilic granules was observed in NG from BMT patients compared with control groups A and B. These data indicate that repopulation after BMT was made by phenotypically less mature NG with dysgranulopoietic features. Differences between autologous and allogeneic BMT patients may be partly related to GM‐CSF usage. In conclusion, NG present immunophenotypic and ultrastructural changes after BMT which may be involved in abnormal NG response against bacterial infections, although further investigation is needed.
A human monoclonal anti‐D antibody which detects a nonconformation‐dependent epitope on the RhD protein by immunoblot
Authors: Apoil P. A. , Reid M. E. , Halverson G. , Mouro I. , Colin Y. , Roubinet F. , Cartron J‐P. , Blancher A. 
Published: November 2003

We describe the first human monoclonal anti‐D (LOR‐15C9) which reacts with a D‐specific motif exposed either on a native form on intact D‐positive red cells or on a denatured form of the RhD protein (33 kD), and detected by immunoblotting. LOR‐15C9 was able to precipitate RhD but not RhcE proteins produced by in vitro transcription‐translation assays. The reactivity of the antibody, using panels of red cells with various partial D phenotypes known to lack some D epitopes and corresponding in RHD gene variants, suggested that LOR‐15C9 reactivity depends on the portion of the RhD polypeptide encoded by the exon 7 (amino acids 314–358). These findings correlate well with the reactivity of LOR‐15C9 with erythrocytes of some nonhuman primates (Dgor‐positive gorillas), but not of chimpanzee and Old or New World monkeys.In membrane proteins from partial DVI red cells, LOR‐15C9 detected two proteins of molecular weight 33 and 21 kD; the presence of the latter was specific for category DVI and presumably represented the product of an alternatively spliced RHDVI transcript in these cells. This is consistent with the finding that LOR‐15C9 can precipitate a shortened D protein mutant resulting from in vitro transcription‐translation and lacking amino‐acids 163–313 encoded by exons 4–6. In addition, a 21 kD band polypeptide was detected by immunoblot in all red cell samples but D−−, using a rabbit anti‐Rh polypeptide antibody (MPC8) raised against the C‐terminal domain of Rh proteins. This 21 kD polypeptide most probably results from the translation of an alternatively spliced RHCE gene transcript.This study demonstrates that LOR‐15C9 detects an epitope on the RhD protein that is independent of the membrane environment, and therefore could be a useful tool for the study of RhD polypeptides.
Allogeneic blood or marrow transplantation for chronic lymphocytic leukaemia: timing of transplantation and potential effect of fludarabine on acute graft‐versus‐host disease
Authors: Khouri Issa F. , Przepiorka Donna , Van Besien Koen , O'Brien Susan , Palmer Judy L. , Lerner Susan , Mehra Rakesh C. , Vriesendorp Huibert M. , Andersson Borje S. , Giralt Sergio , Körbling Martin , Keating Michael J. , Champlin Richard E. 
Published: November 2003

The outcome of allogeneic haemopoietic transplants including the rate of immune complications for patients with chronic lymphocytic leukaemia (CLL) refractory to or relapsing after chemotherapy with fludarabine was analysed.Fifteen patients with advanced CLL who received allogeneic transplantation were prospectively analysed. All patients had previously received chemotherapy with fludarabine for 3–15 courses; 12 were refractory. The median number of circulating CD4^plus; and CD8^plus; lymphocytes at the time of transplant was 0.49 ×109 l and 0.23 ×109 l, respectively. One patient was transplanted from a one HLA‐antigen mismatched unrelated donor. Three others received a one or two antigen mismatched graft and 11 had HLA‐identical sibling donors. Patients received cyclosporine or tacrolimus in addition to methotrexate or methylprednisolone for prophylaxis of acute graft‐versus‐host disease (aGVHD).Fourteen patients engrafted; one patient had graft failure, but recovered after therapy with intravenous immunoglobulin. 13 (87%) achieved complete remission (CR). Nine (53%) remain alive and in CR with a median follow‐up of 36 (range 3–60) months. None developed visceral graft‐versus‐host disease. These data compared favourably to published reports in other leukaemia patients and for patients with CLL who received a comparable immunosuppressive therapy but without prior fludarabine exposure.This data indicates that allogeneic haemopoietic transplantation can induce durable remission in patients with CLL refractory to fludarabine and that it is reasonable to delay transplantation until failure of fludarabine therapy. It also suggests that prior exposure to fludarabine may decrease the incidence of severe aGVHD, possibly through its immunosuppressive effects. Further studies are warranted to evaluate this observation.
Analysis of the effect of prior therapy on progenitor cell yield: use of a chemotherapy scoring system
Authors: Drake M. , Ranaghan L. , Morris T. C. M. , Nolan L. , Desai Z. R. , Irvine A. E. , Jordan A. , Magill K. , Price S. 
Published: November 2003

A quantitative analysis of peripheral blood stem cell (PBSC) yield, measuring absolute numbers of CD34+ cells × 106/kg and CFU‐C × 104/kg was performed in 74 consecutive patients. The interval or ‘gap’ from the end of previous chemotherapy to the date of priming was recorded in weeks.Geometric mean CD34 and CFU‐C values were significantly higher in patients with a score of ≤ 60 compared to those with score > 60 (P = 0.003 and 0.02, respectively) and a significant difference in CD34 values was also found when scores of ≤ 38 were compared with scores > 38 (P = 0.003), with the difference in CFU‐C values approaching significance (P = 0.08). Patients exposed to toxicity factor 4 drugs had significant lowering of both CD34 and CFU‐C values (P < 0.001 and P = 0.038) and this emerged as the only independent factor when analysed using linear regression. No significant difference in the geometric mean CD34 or CFU‐C values of patients was found in any of the gap categories analysed. Prior exposure to toxicity factor 4 drugs had a significant adverse effect on stem cell yield and should be avoided or minimized prior to stem cell harvesting.
Beta‐thalassaemia in the immigrant and non‐immigrant German populations
Authors: Vetter B. , Schwarz C. , Kohne E. , Kulozik A. E. 
Published: November 2003

In Germany homozygous β‐thalassaemia mainly occurs in the immigrant population from endemic regions. In non‐immigrants β‐thalassaemia is rare. Heterozygous β‐thalassaemia minor, however, is more common and must be considered in the differential diagnosis of hypochromic anaemia. The clinical and molecular data of 221 homozygous patients and 256 non‐immigrant German heterozygous individuals are presented. Clinically, 87% (n =192) of the homozygotes are classified as thalassaemia major (TM) and the other 13% as thalassaemia intermedia (TI). There is a wide spectrum of 39 thalassaemia mutations which occur with relatively low frequencies in individual cases. In 17/29 TI patients ‘mild’ mutations have been found and in 16/29 there are mutations that are associated with increased γ‐globin gene activity. α‐Thalassaemia is rare and found only in 3/29.In the 256 Germans with heterozygous β‐thalassaemia there are 27 different thalassaemia mutations. The three most common are Mediterranean, together accounting for 61%. Also relatively common (5%) is an otherwise rare frameshift mutation of codon 83 (FS83 ΔG). The other mutations occur in < 10 individuals. Two mutations described here are novel. One of them affects position −2 of the intron 1 splice acceptor site (IVSI‐129 A‐G) and the other is a deletion of a single G in codon 15/16 (FS 15/16 ΔG). These data suggest that β‐thalassaemia in Germans was introduced from the Mediterranean in about two‐thirds of cases and that the remaining third has probably originated locally.
Mucormycosis in patients with haematological malignancies: a retrospective clinical study of 37 cases
Authors: Pagano Livio , Ricci Paolo , Tonso Anna , Nosari Annamaria , Cudillo Laura , Montillo Marco , Cenacchi Annarita , Pacilli Leonardo , Fabbiano Francesco , Del Favero Albano ,   GIMEMA Infection Program
Published: November 2003

A retrospective study of 37 patients with haematological malignancy (21 acute myeloid leukaemia, 11 acute lymphoid leukaemia, two lymphoma, two hairy cell leukaemia, one Hodgkin's disease) and histologically documented mucormycosis was conducted to evaluate the clinical characteristics and ascertain the factors which influenced the outcome from mycotic infection. Patients were admitted to 18 haematology divisions in tertiary care or university hospitals in Italy between 1987 and 1995.Fever, thoracic pain, dyspnoea and cough were the most frequent presenting symptoms. At the onset, 89% patients were neutropenic (neutrophil counts < 0.5 × 109/l) with a median duration of previous neutropenia of 14 d (range 6–60). The most frequent sites of infection were lungs (81%), CNS (27%), sinus (16%), liver (16%) and orbital space (10%). Only three patients were asymptomatic. A correct in vivo diagnosis was made in only 13 (35%) patients. When performed, thoracic and cranial CT scan were the most useful diagnostic investigations. Despite the fact that 26 febrile patients were treated with empirical antifungal treatment, 28 of the 37 patients (76%) died from fungal infection at a median time of 17 d from the onset of clinical symptoms. Nine patients were cured by antifungal therapy plus, in five cases, radical surgery procedures.An analysis of factors influencing outcome demonstrated that the resolution of chemotherapy‐induced neutropenia and prolonged treatment with amphotericin B and, if feasible, radical surgical debridement treatment, were significantly correlated with recovery from infection.Mucormycosis, a rare filamentous fungal infection that occurs most frequently in neutropenic acute leukaemia patients, is characterized by a high mortality rate. Extensive and aggressive diagnostic and therapeutic procedures are essential to improve the prognosis in these patients.
p53 abnormalities in CLL are associated with excess of prolymphocytes and poor prognosis
Authors: Lens Daniela , Dyer Martin J. S. , Garcia‐Marco Jose M. , De Schouwer Pierre J. J. C. , Hamoudi Rifat A. , Jones David , Farahat Nahla , Matutes Estella , Catovsky Daniel 
Published: November 2003

To determine the role of the p53 gene in chronic lymphocytic leukaemia (CLL) and its possible involvement in the pathogenesis of a progressive form of CLL characterized by > 10% prolymphocytes (CLL/PL), we selected 32 cases, 17 with typical morphology and 15 CLL/PL. The extent of inactivation of p53 was examined by assessing loss of heterozygosity (LOH) at 17p13.3, by sequencing the highly conserved region (exons 5–9) of the p53 gene and by analysing p53 protein expression. LOH was detected in 8/28 (29%) cases, p53 mutations in 5/32 (16%) cases and p53 expression in 5/27 (19%) cases. Overall 11 cases (30%) had p53 abnormalities of which eight cases had CLL/PL. There was a significant association between CLL/PL and p53 abnormalities (P = 0.05); 75% of cases with LOH, 80% of p53 mutations and 80% of cases positive for p53 protein had CLL/PL. Thus, p53 inactivation is the first gene abnormality identified so far to be involved in the development of CLL/PL. All the cases with typical CLL and p53 abnormalities had only one allele affected whereas 4/6 CLL/PL had both alleles inactivated. This difference in the extent of p53 inactivation suggests that accumulation of p53 abnormalities may be associated with progression of CLL to CLL/PL.CLL cases with p53 abnormalities were characterized by a higher incidence of stage C (P < 0.025), a higher proliferative rate (P = 0.05), short survival (P < 0.005) and resistance to first‐line therapy (P < 0.02) but not to nucleoside analogues. Analysis of the correlation between p53 status and incidence of trisomy 12 by fluorescence in situ hybridization (FISH) showed that trisomy 12 was more frequent in cases without p53 abnormalities, suggesting that trisomy 12 and p53 may represent different pathways of transformation in CLL.
Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study
Authors: Lowe G. D. O. , Lee A. J. , Rumley A. , Price J. F. , Fowkes F. G. R. 
Published: November 2003

We examined the relationships of whole blood viscosity and its major determinants to incident cardiovascular events (ischaemic heart disease and stroke) in a prospective study of a random population sample of 1592 men and women aged 55–74 years (the Edinburgh Artery Study). 272 fatal and non‐fatal cardiovascular events occurred during 5 years of follow‐up (cumulative incidence 17.1%). Age and sex adjusted mean levels of blood viscosity (3.70 v 3.55 mPa.s), haematocrit (46.2 v 45.7%), haematocrit‐corrected blood viscosity (3.57 v 3.48 mPa.s), plasma viscosity (1.35 v 1.33 mPa.s) and fibrinogen (2.88 v 2.67 g/l) were significantly higher in subjects who experienced events than in subjects who did not. The relationships of these rheological variables to cardiovascular events were at least as strong as those of conventional risk factors (smoking habit, diastolic blood pressure, and low‐density lipoprotein cholesterol). After adjustment for these conventional risk factors, the associations of blood viscosity and haematocrit remained significant for stroke, but not for total events; whereas the associations of plasma viscosity and fibrinogen remained significant for total events and for stroke.These findings suggest that increased blood viscosity may be one plausible biological mechanism through which increases in haematocrit and fibrinogen may promote ischaemic heart disease and stroke. Randomized controlled trials of viscosity reduction in the prevention of cardiovascular events (e.g. by lowering high levels of haematocrit or plasma fibrinogen) are suggested.
Analysis of T‐cell clonality in bone marrow of patients with acquired aplastic anaemia
Authors: Melenhorst J. Joseph , Fibbe Willem E. , Struyk Linda , Van DerElsen Peter J. , Willemze Roel , Landegent James E. 
Published: November 2003

Acquired aplastic anaemia (AA) represents a state of bone marrow (BM) failure which is characterized by BM hypocellularity and pancytopenia. It has been hypothesized that in some AA patients, bone marrow failure is secondary to the targeted destruction of haemopoietic stem cells by autoreactive T cells. The response of T cells to antigenic stimulation has been shown, in a number of animal models and in autoimmune diseases, to result in the (oligo)clonal expansion of positively reacting T cells. For this reason, we studied the utilization of 24 T‐cell receptor‐β variable gene segments (TCRBV) and the clonality in BM aspirates and peripheral blood (PB) of seven AA patients. BM from transplant donors served as controls. Determination of TCRBV gene segment usage revealed no significant differences between patients and controls.Clonality within each family was analysed by single‐strand conformation polymorphism (SSCP) analysis. Clonal and clonally predominant bands were seen in BM of three AA patients in five to eight TCRBV families. Clonal rearrangements were encountered less often in BM of control subjects. In conclusion, our results suggest an antigen‐driven T‐cell response in the BM of predominantly AA patients resulting in oligoclonal T‐cell outgrowth.
Prompt epithelial damage and restitution processes in allergen challenged guinea‐pig trachea in vivo
Authors: ERJEFÄLT J. S. , KORSGREN M. , NTLSSON M. C. , SUNDLER F. , PERSSON C. G. A. 
Published: November 2003

SummaryBackground
Little is known about the induction and the morphology of epithelial damage, and of the ensuing epithelial restitution processes in allergic airways.Objective
To examine epithelial damage and restitution in allergen challenged guinea‐pig trachea.Methods
Whole‐mount techniques, transmission and scanning electron microscopy, cryosectioning, and histochemical staining were used. Cell proliferation was monitored by BrdU‐immunohistochemistry.Results
Allergen challenge produced patchy, crater‐like, and leucocyte‐rich epithelial damage sites. At 1, 5, and 24 h damage was associated with poorly differentiated epithelial restitution cells. Already at 1 h the epithelial craters had a floor of flattened restitution cells and the damaged areas comprised < 1% of the mucosal surface area (whole‐mount preparations). In contrast, cryo sections displayed large areas (∼ 20%, 1 h) of denudation. Epithelial, and subepithelial (fibroblasts, smooth muscle) proliferation was increased 5 and 24 h after challenge (P < 0.01).Conclusion
Within 1 h allergen challenge has induced patchy damage sites where epithelial restitution is already advanced; although easily produced by cryosectioning frank denudation was not evident in whole‐mount preparations. The present findings may explain the well maintained, functional tightness of allergic airways displaying epithehal damage, shedding, and even denudation. The present data also suggest the possibility that epithelial damage‐restitution may be causative to allergic airway remodelling.
Dysfunction of guinea‐pig pulmonary surfactant and type II pneumocytes after repetitive challenge with aerosolized ovalbumin
Authors: LIU M. , WANG L. , HOLM B. A. , ENHORNING G. 
Published: November 2003

SummaryBackground
Asthma symptoms may partially be caused by a surfactant dysfunction. The inflammatory reaction, so characteristic of asthma, involves a protein invasion of airways which harmfully affects the surfactant function. However, mild asthma attacks might also impede the surfactant synthesis in alveolar type II cells.Objective
The present study evaluates the hypothesis that type 11 pneumocyte metabolic function might be disturbed in a model of mild asthma.Methods
Immunized, as well as not immunized control guinea‐pigs, were challenged three times at two‐day intervals with 0.04% ovalbumin aerosol. Bronchoalveolar lavage (BAL) was performed one day after the last challenge and the fluid was evaluated for surface activity, and content of phospholipids and proteins. Alveolar type II cells were isolated and their ability to incorporate a 3H labeled surfactant precursor was evaluated.Results
BAL fluid from immunized and challenged animals showed less surface activity (P < 0.01) when compared with BAL fluid from controls, not immunized but challenged. Most likely the reduced surface activity was caused by a 14% increase in the protein concentration (P < 0.05). Isolated type II cells from immunized and challenged animals had 33% less phospholipids than cells from controls (P < 0.05), and phosphatidylcholine synthesis was reduced 35% (P < 0.05).Conclusion
Conclusion These results suggest that the synthesis, intra‐cellular storage, and biophysical activity of surfactant are decreased in an intermittent and mild form of asthma.