bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production of granulopoiesis‐stimulating and ‐inhibiting activities by T cells associated with malignant cells in lymphomas
Authors: Piccinni Marie‐Pierre , Jacob Marie‐Christine , Bonnefoix Thierry , Sotto Marie‐France , Pegourie Brigitte , Couderc Pierre , Sotto Jean‐Jacques 
Published: March 2008

SummaryThe possible role of T lymphocytes in the formation of granulomatous reactions seen in certain malignant lymphoid tumours was investigated by measuring the granulopoietic colony‐stimulating activity (CSA) and granulopoietic‐inhibiting activity (IA) produced by stimulated T‐lymphocytes isolated from peripheral blood, spleen and lymph nodes of patients and normal subjects.Lymph‐node T‐cells from patients with benign lymphoid hyperplasia, B‐cell non‐Hodgkin's lymphoma (B‐NHL), and non‐granulomatous Hodgkin's disease (HD) showed no CSA, but the cells produced [A of 40 ± 23%, 40 ± 24% and 50·5 ± 22·5% respectively. The corresponding cells from patients with HD accompanied by granulomatous reactions produced CSA of 6·85 ± 6·5 u/μl and IA of 23·5 ± 21%.The presence of a granulomatous reaction in malignant lymphoma was correlated with the stimulation of granulopoiesis in vitro by T lymphocytes associated with malignant cells. A correlation was demonstrated between neutrophilic and eosinophilic colonies obtained in vitro under the influence of CSA‐producing T cells isolated from malignant lymphomas and the neutrophils and eosinophils present in the granuloma. These results showed that tumour‐infiltrating T cells play a role in the presence of granulomatous reactions seen in lymphomas.Peripheral‐blood T cells from healthy subjects, and from patients with B‐NHL, or with HD unaccompanied by granulocytic reactions produced CSAs of, respectively, 5 ± 0·5 u/μl, 4·8 ± 2·2 u/μl and 5·3 ± 0·4 u/μl, and IAs of 45 ± 18%, 50 ± 5·5% and 50·5 ± 7% respectively. The corresponding values for HD patients with granulocytic reactions were CSA, 17 ± 15·5 u/μl, and IA, 9·5 ± 9%. No correlation was demonstrated between neutrophilic colonies obtained in vitro under the influence of HD blood T cells and neutrophils present in blood. Only one correlation was found: between the percentage of eosinophilic colonies and the number of blood eosinophils. HD blood T cells did not seem to explain completely granulocytic reactions seen in blood.
The C–T substitution in the distal CACCC box of the β‐globin gene promoter is a common cause of silent β thalassaemia in the Italian population
Authors: Ristaldi M. S. , Murru S. , Loudianos G. , Casula L. , Porcu S. , Pigheddu D. , Fanni B. , Sciarratta G. V. , Agosti S. , Parodi M. I. , Leone D. , Camaschella C. , Serra A. , Pirastu M. , Cao A. 
Published: March 2008

SummaryThis paper describes four families of Italian descent in each of which the propositus had the clinical phenotype of thalassaemia intermedia, resulting from the compound heterozygous state for high HbA2β thalassaemia and type I silent β thalassaemia. Direct sequencing on amplified DNA and/or oligonucleotide analysis detected, in all families but one, the compound heterozygous state for codon 39 nonsense mutation and the C‐T substitution at position – 101 in the distal CACCC box of the β‐globin gene promoter (βth–101). Members of these families who are heterozygous for high HbA2β thalassaemia showed the codon 39 nonsense mutation, while those with the clinical phenotype of silent β thalassaemia had the βth–101 mutation. In the remaining family, the propositus and one of his siblings had the compound heterozygous state for a molecularly undefined high HbA2β thalassaemia and the βth–101 mutation in combination with the triple α globin gene arrangement. These patients showed a more severe thalassaemia intermedia like clinical phenotype as compared to those with the same β‐globin genotype and a normal α‐globin gene arrangement. In the families investigated the βth–101 was always associated with haplotype I. A group of patients with thalassaemia intermedia from Southern Italy, either homozygous or heterozygous for haplotype I and in whom previous studies had failed to define the mutation in one of the β thalassaemia globin genes, were screened by oligonucleotide analysis for the presence of the βth–101. Three out of nine were positive. These results indicate that the βth–101 mutation is a common cause of the type I silent β thalassaemia phenotype in the Southern Italian population.
Prevalence of haemochromatosis amongst asymptomatic Australians
Authors: Leggett Barbara A. , Halliday June W. , Brown Nigel N. , Bryant Stewart , Powell Lawrie W. 
Published: March 2008

SummaryWe determined the prevalence of iron overload due to homozygous haemochromatosis in an asymptomatic Australian (predominantly Caucasian) population by surveying 1968 employees of two large corporations. Subjects were screened by measurement of transferrin saturation and serum ferritin concentration and, in all subjects with elevation of both indices, percutaneous liver biopsy was performed to establish whether significant iron overload was present. The prevalence of iron overload due to haemochromatosis in this population was 0·36%. The prevalence rate was not significantly different between males and females, suggesting that this autosomal recessive disease is expressed equally in females given an adequate dietary iron supply. The positive predictive value of a transferrin saturation consistently >45% together with an elevated serum ferritin concentration was 64%. It is concluded that the prevalence of significant iron overload due to homozygous haemochromatosis warranting treatment is approximately 1:300 and that transferrin saturation should be included in existing adult health screening programmes.
Correlation of chromosome abnormalities with laboratory features and clinical course in B‐cell chronic lymphocytic leukaemia
Authors: Oscier D. G. , Stevens J. , Hamblin T. J. , Pickering R. M. , Lambert R. , Fitchett M. 
Published: March 2008

Summary141 patients with B‐cell chronic lymphocytic leukaemia (B‐CLL) have been studied for a minimum of 12 months and a maximum of 25 years. 30 of 133 patients (32·5%) had greater than 10% FMC7 positive peripheral blood lymphocytes and 19 of 131 patients (14·5%) had a serum or urinary paraprotein. At presentation 88 patients were stage A0, 18 A1, 18A2, 11B and six C. 44 (31%) had progressive disease and 42 (30%) died during the study period. 63 patients had a normal karyotype, 75 a clonal abnormality and in three no metaphases were obtained. The finding of a complex karyotypic abnormality was significantly associated with λ surface phenotype (P<0·01), and the presence of > 10% FMC7 positive cells (P<0·025), and the presence of a paraprotein (P<0·025). Patients whose leuk‐aemic cells had a complex karyotype and those with stuuctural abnormalities of chromosomes 14 and 6 required treatment earlier than those with a normal karyotype.
Clinicopathological diagnosis and treatment of malignant histiocytosis
Authors: Sonneveld Pieter , Lom Kirsten van , Kappers‐Klunne Mies , Prins M. Eric F. , Abels Johannes 
Published: March 2008

Summary. The diagnostic findings of malignant histiocytosis (MH) were analysed in 12 consecutive patients in a single institution. Most patients presented with systemic symptoms and lymphadenopathy (92%), splenomegaly (100%) and hepatomegaly (67%). Neurologic symptoms were present in three patients, while involvement of other organs was present in five patients. The incidence of severe thrombocytopenia was 92%, of anaemia 92% and of leucocytopenia 67%. Serum angiotensin converting enzyme, α1‐antitrypsin and lysozyme were independently increased in 6/9, 3/10 and 1/9 patients respectively. High serum levels of tumour necrosis factor (TNF) were present in 3/10 patients, while serum levels of interleukin‐1 were normal in 10/10 patients. Histologic evidence of MH was obtained in all patients by repeated biopsies of involved tissues. Four patients died prior to treatment. Seven patients were treated with combination chemotherapy, consisting of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or MOPP (chloromethine, vincristine, procarbazine, prednisone), in some cases followed by non‐cross‐resistant second line chemotherapy, if no complete response was attained. The response rate of treated patients was 5 7%, and progression was observed in two patients. The median duration of response was 38 months. Three patients are alive without evidence of disease and off therapy (30+, 83+, 85+ months).Although MH is a potentially lethal disease, combination chemotherapy may offer a chance for cure in some patients.
Translocation of bcl‐2 gene in non‐Hodgkin's lymphomas in Hong Kong Chinese
Authors: Loke S. L. , Pittaluga S. , Srivastava G. , Raffeld M. , Ho F. C. S. 
Published: March 2008

Summary. The close association between translocation of the proto‐oncogene bcl‐2 and follicular lymphomas has been well established in Caucasian patients and the de‐regulation of bcl‐2 has been implicated in follicular lymphomagenesis. Similar molecular structural alterations have also been detected in diffuse lymphomas with a previous history of a follicular pattern as well as in a smaller proportion of de novo diffuse lymphomas.There is a lower incidence of follicular lymphomas in Chinese. In order to investigate further this phenomenon, we used bcl‐2 translocation as a genetic marker of follicular lymphomas, to study 31 cases of B cell non‐Hodgkin's lymphomas in Chinese patients by Southern blot analysis.Eight out of 16 cases of follicular lymphomas showed bcl‐2 translocation with involvement of the major breakpoint region (MBR). Six of these cases utilized breakpoints within the 4.3 kb HindIII fragment, while in two cases the breakpoints were more dispersed, but still within the BamHI fragment. An additional case of follicular lymphoma showed translocation of bcl‐2 gene with involvement of the minor cluster region (mcr), making a total of nine out of 16. None of the 15 cases of diffuse lymphomas showed similar molecular structural alterations.These data show that bcl‐2 translocation is present in 57% of follicular lymphomas in Chinese patients, and support the notion that bcl‐2 translocation is a consistent marker for follicular lymphomas irrespective of ethnic differences. As the translocation is not detected in the diffuse lymphomas, there is no evidence to suggest that the low incidence of follicular lymphomas in Chinese patients is due to a greater tendency for follicular tumours to progress rapidly and present as diffuse lymphomas.
Capacity to produce interleukin 2 is impaired in haemophilia in the absence and presence of HIV 1 infection
Authors: Madhok R. , Gracie J. A. , Smith J. , Lowe G. D. O. , Forbes C. D. 
Published: March 2008

Summary. Capacity to produce interleukin‐2 (IL‐2) was measured in haemophiliacs from a well‐defined treated cohort. Patients were selected on the basis of HIV‐1 antibody status, mean annual dose of clotting factor and liver disease severity. T‐cell subsets and peripheral blood mononuclear cell proliferation to Mycobacterium tuberculosis purified protein derivative (PPD) were also measured.Haemophiliacs had reduced IL‐2 production, independent of HIV‐1 antibody status, mean annual dose of clotting factor concentrate used and liver disease severity. In HIV‐1 antibody positive patients reduced levels correlated with PPD proliferative responses (r=0.6, P=0.04) and CD8+ve (r=05, P=0.05) but not CD4 + ve cell numbers (r= 0.3, P=0.2). No such correlations were seen in HIV‐1 antibody negative patients.Reduced IL‐2 production in HIV‐1 antibody negative haemophiliacs was due to a qualitative defect. In HTV‐1 positive patients a qualitative defect in T lymphocytes that selectively proliferate in response to PPD was observed. CD4 + ve cell numbers were reduced in HIV‐1 positive patients.
Clonal karyotype abnormalities and clinical progress in the myelodysplastic syndrome
Authors: Geddes A. D. , Bowen D. T. , Jacobs A. 
Published: March 2008

Summary Summary Clonal karyotype abnormalities in 124 patients with myelodysplastic syndrome are reviewed. 36% of patients had abnormalities at referral, the most common being 5q ‐, +8 and lesions of chromosomes 7 and 20. Reduced survival was associated with the presence of either single or multiple clonal abnormalities at referral, abnormalities of chromosome 7 or 8 (either alone or with other lesions) and exclusively abnormal metaphases. The presence of 5q ‐alone did not appear to affect survival.Sequential studies were carried out in 77 patients of whom 12 showed karyotypic evolution. Reduced survival was observed in patients with an evolving karyotype but appeared to be due almost entirely to evolution in those patients whose initial karyotype was normal. Leukaemic transformation occurred more commonly in patients with an abnormal karyotype, particularly those with multiple abnormalities, and in patients with an evolving karyotype. Although the first appearance of an abnormal karyotype or an apparent evolution are important phenomena, it is probable that in some cases they merely represent expansion of a previously existing clone that has escaped detection. The distinction between true karyotypic evolution or clonal expansion and statistical variations due to small sample size and variability of samples may be difficult but needs to be taken into account in considering clinical significance.
Teicoplanin in the treatment of Gram‐positive bacteraemia in neutropenic patients
Authors: Venditti A. Micozzi M. , Amadori S. , Pulsoni A. , And C. Tirindelli , Martino P. 
Published: March 2008

Summary The increasing incidence of bacteraemia caused by Gram‐positive bacteria in neutropenic patients prompted the authors to evaluate, in a prospective trial, the role of teicoplanin in the treatment of this infection. Over a 15‐month period. 76 cases of bacteraemia (out of 265 evaluable episodes of fever) were observed at the Division of Haematology. University La Sapienza. Kome. Of the 76 cases studied, 46 (60%) were caused by Gram‐positive bacteria and 28 (37%) were caused by Gram‐negative bacilli. All febrile episodes were treated randomly and empirically with piperacillin plus amikacin with or without teicoplanin. Overall, 41 (54%) of the 76 cases of bacteraemia responded to the initial antibiotic regimen: with subsequent modifications the response rate rose to 96%.In the treatment of Gram‐positive bacteraemia. first‐line administration of teicoplanin was found to be associated with early defervescence and with a significantly higher rate of success without modification of treatment (P < 0.01). Addition of teicoplanin as second‐line therapy produced a favourable outcome in 12 (70%) out of 17 cases of bacteraemia unresponsive to the initial piperacillin + amikacin regimen. No cases of Gram‐positive bacteraemia associated with septic shock or adult respiratory distress syndrome were observed in either treatment group. Only two late deaths were observed, and these occurred in patients with streptococcal septicaemia who were not receiving early teicoplanin.The above data do not endorse the use of glycopeptide antibiotics in the early treatment of fever in neutropenic patients: rather, these compounds should be reserved for proven or presumed Gram‐positive infections which do not respond to initial beta‐lactam/aminoglycoside treatment.
Ceftazidime plus teicoplanin versus ceftazidime plus amikacin as empiric therapy for fever in cancer patients with granulocytopenia
Authors: Meunier F. , Vander Auwera P. , And M. Aoun , Bron D. 
Published: March 2008

Summary In a prospective randomized study, 100 episodes of fever (>38°C) and granulocytopenia (<1000/μ1) in cancer patients were empirically treated with ceftazidime (2 g every 8 h) plus teicoplanin (400 mg every 8 h on day 1: 400 mg every day thereafter) or ceftazidime (2 g every 8 h) plus amikacin (500 mg every 8 h).Bacteraemia. clinically documented infection and possible infection were documented in seven. 11 and 19 patients treated with ceftazidime plus teicoplanin and in 11, four and 17 patients treated with ceftazidime plus amikacin. Overall, the response rate was similar in the two groups of patients as was the need for treatment modifications and the rate of death.For documented Gram‐positive bacteraemia, the response rate was 2/5 patients treated with ceftazidime plus teicoplanin and 2/7 with ceftazidime plus amikacin: for documented Gram‐negative bacteraemia. the response rate was 1/2 and 3/4 patients respectively. No breakthrough bacteraemia was observed. Tolerance was excellent. although renal toxicity (elevation of serum creatinine) was observed in three patients treated with ceftazidime plus teicoplanin and in none allocated to ceftazidime plus amikacin.
Role of glycopeptide antibiotics in the treatment of febrile neutropenic patients
Authors: Smith S. R. , Cheesbrough J. , Harding I. , Davies J. M. 
Published: March 2008

Summary The exact timing of the introduction of the glycopeptide antibiotics teicoplanin and vancomycin in the management of the febrile neutropenic patient continues to be controversial. However, there are certain firm criteria now emerging.Bacteraemia can be eradicated with a success rate approaching 100% in cases where the organism can be identified and shown to be sensitive.Approximately 6 5% of cases of soft‐tissue infection, usually occurring with the use of a Hickman or equivalent indwelling catheter, are associated with the presence on culture of Gram‐positive organisms of presumed skin origin. Such infection is an indication for the early use of antibiotics with proven activity against coagulase‐negative staphylococci and diptheroids.Resolution of fever in up to 50% of cases may result from using‘planned progressive therapy’: the introduction of specific Gram‐positive cover in patients who have failed to respond at 48–72 h to regimens such as a ureidopenicillin or a third‐generation cephalosporin with or without an amino glycoside. This approach reduces the number of patients who go on to receive empirical amphotericin B intravenously for presumed fungal infection.Using teicoplanin or vancomycin as first‐line agents in the empirical treatment of first fever in febrile neutropenic patients is perhaps more controversial. Recent developments which include using quinolone‐based prophylaxis more widely and introducing cytokines to reduce the period of neutropenia may increase the likelihood that a neutropenic patient's febrile episode will be due to a Gram‐positive organism.The dilemma of choosing broad‐spectrum monotherapy or targeted combination therapy in this situation remains unresolved. Current studies, however, should help to clarify this situation.Finally, other current studies of teicoplanin and vancomycin as prophylactic agents administered either orally or systemically, may provide additional indications for their use in the neutropenic patient.
Simultaneous expression and regulation of G‐CSF and IL‐6 mRNA in adherent human monocytes and fibroblasts
Authors: Vellenga Edo , Van Der Vinne Bernard , De Wolf Joost Th. M. , Halie M. Ruud 
Published: March 2008

Summary The regulation of granulocyte‐colony stimulating factor (G‐CSF) and interleukin‐6 (IL‐6) mRNA was studied in human adherent monocytes in response to the protein kinase C activator, oleolyl‐acetylglycerol (OAG), the calcium‐ionophore A23187 and the cyclic AMP elevating agents, dibutyryl c‐AMP (DBcAMP), cholera toxin and isobutyl‐methylxanthine (IBMX). G‐CSF and IL‐6 transcripts were simultaneously expressed in response to OAG, A23187, DBcAMP, IBMX and cholera toxin. However, the time course demonstrated a difference; a rapid induction by OAG and A23187 and a delayed pattern by cAMP elevating agents. In addition it appeared that the induction of CSFs by DBcAMP was independent of the adherence procedure or the presence of fetal bovine serum but could be counteracted by the simultaneous addition of H8, an inhibitor of the cAMP dependent kinases.Finally, experiments were performed to study in how far comparable mechanisms operate in other cell types. Human fetal lung fibroblasts were stimulated with A23187. DBcAMP and OAG. All these agents induced simultaneous expression of G‐CSF and IL‐6 mRNA and secretion of proteins, indicating that different signalling pathways exist in both cell types which regulate the expression of both genes.
Book Reviews
Authors: Stuart John , Scully Mike , Whittaker J. A. , Lane David , Machin Samuel J. , Testa N. G. 
Published: March 2008

Book Reviews in This Article: Practical Haematology, 7th edn. Edited by Sir John V. Dacie and S. M. Lewis. The Biology of Antithrombins. By G. Sas. William Dameshek and Frederick Gunz's ‘Leukaemia’, 5th edn. Edited by E. S. Henderson and T. A. Lister. Fibrinogen 4. Current Basic and Clinical Aspects. Edited by M. Matsuda, S. Iwanaga, A. Takada and A. Henschen. Disorders of Haemostasis, 2nd edn. Edited by O. D. Ratnoff and C. D. Forbes. The Biology of Hematopoiesis. Edited by N. Dainiak, E. P. Cronkite, R. McCaffrey and R. K. Shadduck.
Abnormal neutrophil adhesion in sickle cell anaemia and crisis: relationship to blood rheology
Authors: Boghossian S. H. , Nash G. , Dormandy J. , Bevan D. H. 
Published: March 2008

Summary. Defects in neutrophil adhesion and migration may contribute to the susceptibility to infection seen in sickle cell anaemia (SCA). These dynamic defects may be influenced by abnormalities in blood rheology found in this disorder. A whole blood model was used to study neutrophil adhesion in SCA patients: neutrophil adhesion to protein coated glass was quantitated by measuring the rate of disappearance of neutrophils from heparinized whole blood circulating through a perfusion chamber. Twenty‐three adult patients (Hb SS) were studied in asymptomatic steady state, of whom nine were also studied during pain crisis, both before and 4–7 d after conventional therapy. Red cell and granulocyte filter ability and whole blood and plasma viscosity were also measured. The half‐time for disappearance from the perfusion system (t1/2) of neutrophils from patients in the steady‐state was 93·5 ± 8·4 min, compared to 49·1 ± 2·8 min in normal age‐matched controls (P=0·001). In crisis, t1/2 was further prolonged to 170·0 ± 16·1 min (P= 0·01 v. steady state). After therapy, t1/2 decreased to 57·0 ± 4·5 min (P=0·001 v. pre‐therapy state and P= 0·009 v. steady state) and was comparable to Hb AA controls. These findings reveal a neutrophil adhesion defect in SCA which worsens in crisis but is corrected following supportive therapy.Red cell filterability (expressed as average resistance to flow and pore‐clogging particles) and white cell filterability (expressed as pore‐clogging particles) were also abnormal in SCA and were found to correlate with neutrophil adhesion. Plasma viscosity also correlated with adhesion t1/2.The defect appears to be related to abnormal blood flow properties in SCA but the rheological factors cannot fully explain either the steady‐state defect or the marked changes in neutrophil adhesion during crisis.