bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of bone marrow histology in the malignant lymphomas (non‐Hodgkin's): correlation with clinical factors for diagnosis, prognosis, classification and staging
Authors: Bartl R. , Frisch B. , Burkhardt R. , Kettner G. , Mahl G. , Fateh‐Moghadam A. , Sund M. 
Published: March 2008

Summary.Bone marrow biopsies of 678 untreated patients with established malignant non‐Hodgkin's lymphomas (ML) were investigated. The bone marrow was involved in 468 cases, an overall frequency of 69%. The Kiel classification of the ML (based on lymph node histology) was applied and the biopsies were classified: ML lymphocytic 36%, ML ‘hairy cell’24%, ML lymphoplasmacytic/cytoid 24%, ML centrocytic 6%, ML centroblastic/centrocytic 4%, ML lymphoblastic (without ALL) 3%, ML centroblastic 2% and ML immunoblastic 1%. The life tables of the patients were similar whether classified according to the histology of the lymph node or the bone marrow. A multivariate computer based analysis of both clinical and histological data was performed to test their prognostic relevance. The cell type, the proliferation pattern and the extent of infiltration in the bone marrow all proved to be factors of prognostic significance. The results indicate that classification of the ML based on lymph node histology is applicable to the bone marrow, is reproducible and has prognostic significance. Consequently, a bone marrow biopsy is a useful clinical tool for staging and for histological classification of patients with ML.
Studies on quinine‐ and quinidine‐dependent antibodies against platelets and their reaction with platelets in the Bernard‐Soulier syndrome
Authors: van Leeuwen E. F. , Engelfriet C. P. , Kr. vondem Borne A. E. G. 
Published: March 2008

Summary.The sera of 14 patients with quinine/quinidine‐dependent thrombocytopenia were studied in the platelet suspension immunofluorescence test (PSIFT), the 51Cr‐lysis assay and the complement fixation test (CFT).When anti‐Ig or anti‐IgG reagents were used, the PSIFT proved to be a little more sensitive than the 51Cr‐lysis assay and far more sensitive than the CFT. With the PSIFT, it was possible to determine the immunoglobulin class of the antibodies, which in all sera was IgG of the subclass IgGl. In two sera there were also IgG3 antibodies, and in the sera of three patients additional IgM drug‐dependent platelet antibodies were detected.With the anti‐C3 reagent, however, lower titres were observed in the PSIFT than in the 51Cr‐lysis assay, in contrast to the results with other complement‐binding IgG platelet antibodies. The F(ab′), fragments of the antibodies did not react in the PSIFT. This indicates that the Fc part of the antibody is essential for the fixation on the platelet membrane. These findings support the theory that in this syndrome drug‐antibody complexes are formed in the absence of platelets that selectively adhere to the Fc receptor on platelets.The platelets of patients with the Bernard‐Soulier syndrome (BSS) reacted normally with the quinine/quinidine‐dependent antibodies in some of the sera, but not with those in other sera in the PSIFT. However, lysis of BSS platelets was never observed. The results of absorption studies showed a reflection of the results in the PSIFT, indicating that the receptor for the quinine/quinidine‐dependent antibodies is not absent in this disease but altered. Whether a reaction with BSS platelets will take place depends on characteristics of the antibodies.
The 5q‐ chromosome abnormality in haematological disorders:|a collaborative study of 34 cases from the Netheralands
Authors: Kerkhofs H. , Hagemeijer A. , Leeksma C. H. W. , Abels J. , Den Ottolaner G. J. , Somers R. , Gerrilts W. B. J. , Lqangenhuiyuen M. M. A. C. , Van Dem Borne A. E. G. Kr. , Van Hemel J. O. , Geraedts J. P. M. 
Published: March 2008

Summary. Clinical, haematological and cytogenetic data of all patients with an acquired 5q ‐ abnormality, diagnosed in four cytogenetic laboratories, were studied. The 5q‐ arose de novo in 24 patients, while 10 patients exhibited it after radiation and/or chemotherapy. Sixteen cases with a dysmyelopoietic syndrome (DMPS) and one case with acute nonlymphocytic leukaemia (ANLL) had no chromosome abnormalities other than 5q‐ . All nine patients with refractory anaemia (RA) belonging to the de novo group had a normal cell line. So far none of them has transformed to acute leukaemia, while three patients with refractory anaemia with excess of blasts (RAEB), pure red cell aplasia (PRCA) and acquired idiopathic sideroblastic anaemia (AISA), having the 5q‐ in 100% of the cells showed such a transformation. The second group consisted of nine patients with a 5q‐ and additional chromosome abnormalities: three of them died of progression of the disease, while four died of unrelated causes. Eight out of nine patients with a 5q‐ and acute leukaemia, either de novo (five) or secondary (four) to radiation and/or chemotherapy, had additional chromosome abnormalities. Among the changes (partial) monosomy of chromosome 7 was most frequently found.The median survival time of the group of patients with an isolated 5q‐ in the presence of a normal cell line was significantly longer than that of patients with additional chromosomal changes with or without acute leukaemia.All patients with an isolated 5q‐ abnormality showed the previously reported megakaryocytic abnormalities (small mono‐ or bilobulated). In most of the other patients these megakaryocytic abnormalities were also found, whereas others were definitely normal in this respect. A striking and unexplained preponderance of females (1 2 out of 16) was found in the group with an isolated 5q‐ anomaly.All deletions studied with banding techniques appeared to be interstitial but the breakpoints were variable. The shortest region of overlap is near band 5q22.
Functional compartmentation of DNA precursors in human leukaemoblastoid cell lines
Authors: Taheri M. R. , Wickremasinghe R. G. , Hoffbrand A. V. 
Published: March 2008

Summary. Human leukaemoblastoid cell lines were incubated with [3H]t hymidine and used to study the utilization for DNA synthesis and degradation of thymine nucleotides labelled via the salvage pathway. Three types of experiments were performed.(1) Cells were continuously labelled with exogenous [3H]thymidine at 3 7°C to compare the incorporation of label into DNA with the specific radioactivities of thymine nucleotides separated by chromatography on polyethyleneimine‐cellulose. These studies demonstrated whether one or more functional pool of thymine nucleotides was present.(2) Intracellular thymine nucleotide pools were labelled with [3H]thymidine at 13°C, and the cells were subsequently incubated in unlabelled medium at 37°C in order to quantify the percentage of thymine nucleotides incorporated into DNA. The results showed that 18%, 75%, 75% and 91% of intracellular thymine nucleotides were incorporated into DNA during the chase, in Raji (B lymphoid), Nalm‐6 (pre‐B cell), HL60 (myeloid) and KM3 (c‐ALL) cells respectively, whereas Molt4 (Thy‐ALL) cells incorporated 100%.(3) In order to quantify the activity of the degradative pathway for thymine nucleotides in these cell lines, cells were labelled as described in (2) in the presence of cytosine arabinoside (an inhibitor of DNA synthesis). 100%, 90%, 65%, 38% and 20% of labelled thymine nucleotides were degraded in Raji, HL60, Nalm‐6, KM3 and Molt‐4 respectively.These results confirm our previous conclusion (Taheri et al, 1981a, b) that thymine nucleotides are functionally compartmentalized in human cells. If these results with cell lines can be extrapolated to apply to de novo leukaemia cases, they suggest that the degree of compartmentation differs widely between different leukaemia cell types. Thy‐ALL cells utilized all their labelled thymine nucleotides for DNA synthesis, whereas B‐ALL, cells utilized only 18% of their labelled thymine nucleotide nucleotides. Thy‐ALL cells have the smallest degradative thymine pool and degradative capacity whereas B‐ALL cells possess the largest degradative pool and capacity. AML, pre‐B‐ALL, c‐ALL cell lines show intermediate results. If these results reflect those of the normal bone marrow cells from which each of the leukaemias arise, they suggest that with progressive B cell development in the bone marrow, degradative ability for DNA precursors increases and the efficiency of utilization of DNA precursors for DNA synthesis decreases.
Assessment of marrow trephine in relation to staging in chronic lymphocytic leukaemia
Authors: Bartl R. , Frisch B. , Burkhardt R. , Hoffmann‐Fezer G. , Demmler K. , Sund M. 
Published: March 2008

The prognostic value of the Rai clinical staging system and of a series of bone marrow features was examined in 167 untreated patients with CLL. The patients fell into three prognostic groups: those with limited disease, Rai stages 0 and I, median survival 107 months; those with intermediate disease, Rai stage II, median survival 44 months; and those with extensive disease, Rai stages III and IV, median survival 27 months. Two types of infiltration patterns, diffuse and nodular, were found in the bone marrow, and these were associated with significantly different median survival times: 34 and 115 months respectively.It is suggested that diffuse and nodular patterns in the bone marrow relate to the rapidity of progress of the disease rather than to different stages in CLL.The data suggest that a simplified clinical staging system together with an histological classification reflects both the extent as well as the rate of progression of CLL. The course of CLL may be monitored by sequential bone marrow biopsies to assess changes in the proliferation pattern, in the proliferative cell system and in the tumour mass, which give early warning of shifts in the rate of progression and therefore in the prognosis of the disease.
Simplified immunoradiometric assay for factor VIII coagulant antigen
Authors: Thomas K. B. , Howard M. A. , Koutts J. , Firkin B. G. 
Published: March 2008

A simplified, non‐competitive, solid phase immunoradiometric assay has been developed for the quantitation of factor VIII coagulant antigen (VIII:CAg)—the antigenic counterpart of FVIII coagulant activity (VIII:C). Both homologous and heterologous antibodies to human factor VIII (FVIII) were used in this assay. Initially, FVIII in a test sample was attached to immobilized, human IgG obtained from a polytransfused haemophilia A patient with a high titre antibody to VIII:C. The bound FVIII was then detected using rabbit 125I‐IgG specific for human FVIII. The concentration of VIII:CAg correlated well with VIII:C levels in the plasma from normal donors (r= 0.84, n= 15).Homozygote von Willebrand's disease patients had undetectable levels of VIII:CAg in their plasma. Patients with severe haemophilia A (VIII:C < 0.01 u/ml) could be divided into groups on the basis of the VIII:CAg levels, i.e. those having undetectable VIII:CAg and others with measurable VIII:CAg. VIII:CAg detected in normal serum was < 0.002 u/ml.In this assay the use of human antibody to FVIII is considerably decreased compared to other methods for VIII:CAg, and the time‐consuming steps to immunopurify human anti‐FVIII antibody are eliminated.
Uptake and release of transferrin and iron by mitogen‐stimulated human lymphocytes
Authors: Bomford Adrian , Young Stephen P. , Nouri‐Aria Kayhan , Williams Roger 
Published: March 2008

Summary.Phytohaemagglutinin stimulation of human peripheral blood lymphocytes resulted in the expression of transferrin receptors and the uptake of iron into the cells. As assessed from the resistance of the 125I label to pronase, transferrin was rapidly bound and internalized at 37°C, while at 4°C 85% of the 125I label remained on the cell surface and was degraded by the pronase. Over 94% of the 125I label associated with and subsequently released from the cells was acid precipitable, indicating that transferrin was not degraded during its uptake and release. After reincubation for 1 h in fresh medium 70% of the cell associated 125I‐transferrin was released. In contrast, less than 30% of the 59Fe was released, showing that iron was removed from transferrin and retained by the cells.Concentration dependent binding of 125I‐transferrin estimated at 37°C occurred with an apparent Ka of 5·7±1·1 × 107l mol−1 (mean ± SD, n= 4) indicating little variation between cells from different individuals, although the number of transferrin molecules associated with the cells varied greatly from 6·2 × 104/cell to 1·4 × 105/cell. The rate of iron uptake from 59Fe and 125I labelled transferrin at 37°C by the cells from different subjects was also very variable, with a range between 0·46 and 2·27 pg Fe/min/106 cells (n= 6). However, iron uptake did not correlate with the amount of transferrin bound. This suggests that transferrin uptake and the release of iron from the transferrin to the interior of the cell are controlled independently.
Detection of glycoprotein IIb and IIIa by monoclonal antibodies
Authors: Thurlow P. J. , Barlow B. , Connellan J. M. , McKenzie I. F. C. 
Published: March 2008

Summary.Murine monoclonal antibodies were produced against human platelet membranes and screened on platelets by a 125I protein A radioimmunoassay. Several clones produced platelet specific antibodies as they showed no reaction with peripheral blood lymphocytes, neutrophils, bone marrow (excluding megakaryocytes) or several cell lines. Two antibodies (designated anti‐HuPl‐mla and anti‐HuPl‐mlb) were of particular interest in that although platelet specific they were non‐reactive with platelets from a thrombasthenic patient. In functional assays these two antibodies could specifically inhibit ADP and collagen induced aggregation of platelets and release of ATP, retard platelet aggregation and ATP release induced by epinephrine, and inhibit ADP induced platelet fibrinogen binding. These two antibodies appear to recognize glycoproteins IIb and IIIa as analysis by SDS‐PAGE using radiolabelled membranes revealed a two chain structure of molecular weight 112 000 and 122 000 daltons when run after reduction and 87 000 and 140 000 daltons non‐reduced.
Mitogen‐induced stimulation and suppression of erythroid burst promoting activity production by human mononuclear cells
Authors: Zuckerman Kenneth S. , Haak Mary 
Published: March 2008

Summary.Exposure of human peripheral blood mononuclear cells or highly enriched monocytes to various plant lectins substantially alters their production of erythroid burst promoting activity (BPA). Neither unstimulated, nor mitogen stimulated, enriched T lymphocytes produced demonstrable BPA. Each of the lectins tested resulted in a different pattern of alteration of BPA production by mononuclear cells. Increasing concentrations of phytohaemagglutinin (PHA) caused a progressive increase in BPA production up to a plateau level at concentrations above 0·25–0·5 μ1/ml. Concanavalin A (Con A) at concentrations of 0·05–0·1 μg/ml stimulated BPA production, but Con A concentrations > 1 μg/ml never augmented BPA production by mononuclear cells. Pokeweed mitogen inhibited BPA production by mononuclear cells in a concentration‐dependent manner. Since PHA and Con A can bind to and stimulate both monocytes/macrophages and T lymphocytes, some production of BPA by stimulated T cells in the presence of monocytes cannot be ruled out. Earlier studies demonstrated that T cells augment monocyte production of BPA. Thus, monocyte–T cell interactions, as well as activation of monocytes and perhaps lymphocytes, play an important role in regulation of BPA production in vitro.
Plasma fibronectin in myeloproliferative disorders and chronic granulocytic leukaemia
Authors: Norfolk D. R. , Bowen M. , Roberts B. E. , Child J. A. 
Published: March 2008

Summary.A significant reduction of plasma fibronectin levels was found in polycythaemia vera and myelofibrosis, the lowest levels being found in patients with marked splenomegaly. Plasma fibronectin concentration was normal in essential thrombocythaemia, and only modest reduction was seen in chronic granulocytic leukaemia in either controlled chronic phase or blast cell crisis. In a patient with myelofibrosis, the plasma fibronectin rose from less than 100 mg/l to 177 mg/l after splenectomy. Possible explanations include increased consumption of plasma fibronectin in the expanded mononuclear phagocyte system present in the liver and spleen, reduced hepatic synthesis, and the clearance of circulating immune complexes. Low plasma fibronectin concentrations may increase susceptibility to infection.
The effects of surgery on the activity of neutrophil granule proteins
Authors: Davies J. M. , Sheppard K. , Fletcher J. 
Published: March 2008

Summary. Activities of the neutrophil granule‐associated proteins β‐glucuronidase, lysozyme and vitamin B12 binding protein were measured, serially, in the cells and serum of 10 patients undergoing total abdominal hysterectomy.The neutrophil leucocytosis which followed total abdominal hysterectomy was accompanied by a fall in the intraneutrophilic activities of all three granule‐associated proteins.Intraneutrophilic lysozyme activity and intraneutrophilic vitamin B12 binding capacity were maximally reduced within 4 h of surgery and fell to 62 ± 13% (mean ± SEM) and 63 ± 9% of their preoperative levels, respectively. This contrasted with the activity of intraneutrophilic β‐glucuronidase which was not maximally reduced until 24 h post‐surgery when a fall to 80 ± 6% of the preoperative level was observed.By the fifth postoperative day activities of the three intraneutrophilic granule proteins were increasing and approaching those observed preoperatively.Serum lysozyme and plasma unsaturated vitamin B12 binding capacity (UBBC) rose steadily following surgery and were significantly elevated by the fifth postoperative day.It is suggested that activation and in vivo degranulation of circulating neutrophils may be responsible for these changes in activity of neutrophil granule proteins following surgery.
Nephrotoxicity in bone marrow transplant recipients treated with cyclpsporin A
Authors: Hows J. M. , Chipping P. M. , Fairhead S. , Smith J. , Baughan A. , Gordon‐Smith E. C. 
Published: March 2008

Summary. Cyclosporin A (CyA) is a valuable post graft immunosuppressive agent in allogeneic bone marrow transplantation. The use of CyA is associated with a reduction in severity of graft versus host disease and improved marrow engraftment.A major side effect of CyA is nephrotoxicity. In 33 patients studied during the first 4 weeks of therapy there is a close correlation between trough (12 h) serum cyclosporin A concentrations and plasma creatinine (r=0·93, P < 0·001) and urea (r=0·88, P < 0·001). Trough CyA serum concentrations of > 500 ng/ml are potentially nephrotoxic. Other risk factors for early nephrotoxicity in cyclosporin therapy are the concurrent use of aminoglycoside antibiotics (P=0·01) and hyperbilirubinaemia (P=0·01). Early nephrotoxicity can be prevented by maintaining trough CyA levels in the range 100–400 ng/ml.During prolonged CyA therapy, cumulative renal impairment can occur and nephrotoxic episodes associated with microangiopathic peripheral blood changes and hypertension are seen in a minority of patients.
Circulating pluripotent haemopoietic cells in patients with myeloproliferative disorders
Authors: Douer Dan , Fabian Ina , Cline Martin J. 
Published: March 2008

Summary. Peripheral blood cells of 17 patients with myeloproliferative disorders were grown in vitro to form mixed colonies (CFU‐mix). CFU‐mix were found in four of nine patients with chronic phase chronic myelocytic leukaemia (CML) at levels 28‐ to 132‐fold higher than the upper limits of normal subjects. These patients also had higher than normal levels of circulating granulocyte‐macrophage (CFU‐GM) and erythroid (BFU‐E) progenitors. Development of blastic crisis was associated with disappearance of CFU‐mix from the blood.CFU‐mix was detected in the blood of three of five patients with polycythaemia vera (PV) and two patients with myelofibrosis with myeloid metaplasia (MMM) at levels slightly higher than those of normal subjects. Our results are consistent with a clonal expansion of multipotent haematopoietic precursor cells in CML and abnormal kinetics of this cell in CML, PV and MMM.
Cellular abnormalities of folate deficiency
Authors: Steinberg Stephen E. , Fonda Susan , Campbell Caryl L. , Hillman Robert S. 
Published: March 2008

Summary. To trace the development of folate‐deficient abnormalities of morphology and DNA synthesis, Friend erythroleukaemia cells were grown in media containing 102, 103 and 104 ng of [3H]PteGlu1/ml and then transferred to folate‐free media. Parameters examined were: intracellular folate levels; growth potential; morphology; dU suppression; and DNA content by flow microfluorimetry. The most sensitive indicators of folate‐deficient cell growth were those related to DNA synthesis (dU and flow microfluorimetry). These became abnormal at intracellular folate levels of 0.2–0.5 ng/106 cells and markedly so below 0.1 ng/106 cells. Morphological criteria were less sensitive. Cells became megaloblastic at intracellular folate levels below 0.06 ng/106. The capacity of the cells to replicate in folate‐free media was a function of the intracellular folate (ICF): duplications = 4.01+ln(ICF)/0.67 (r = 0.993, P<0.001).These studies demonstrate that regardless of initial intracellular folate levels, cellular stigmata of folate deficiency appear when cellular folate falls below 3 × 105 molecules per cell (dU and flow microfluorimetry) and cells lose the capacity for further replication below 7–10 × 105 molecules. The intracellular folate level not only predicts early defects, but also determines the replicative capacity.
Interference of IgG, IgG aggregates and immune complexes in tests for platelet autoantibodies
Authors: Helmerhorst F. M. , Smeenk R. J. T. , Hack C. E. , Engelfriet C. P. , Borne A. E. G. Kr. von dem 
Published: March 2008

Summary. Three techniques, based on the antiglobulin principle, used for the detection of autoantibodies against platelets, were compared; the antiglobulin consumption assay (QACA), the platelet radioactive antiglobulin test (PRAT) and the platelet suspension immunofluorescence test (PSIFT).Upon incubation of normal donor platelets with purified IgG, in concentrations higher than that in serum, an increased amount of platelet‐associated IgG was demonstrated only in the QACA. Upon incubation with aggregated IgG, all three tests became positive, but the PSIFT only with high concentrations of aggregates. Binding of soluble C1q‐binding immune complexes (IC), which consisted of tetanus toxoid and IgG antitetanus antibodies (TaT) to normal donor platelets, was only detectable in the QACA. However, a positive result was obtained in all three tests with platelets incubated with soluble DNA‐IgG‐antiDNA antibodies (DaD) IC. Fixation of the platelets with paraformaldehyde prevented the binding and the detection of the DaD‐IC, but not of IgG, aggregated IgG or TaT‐IC.Eluates from platelets incubated with aggregated IgG, TaT‐ or DaD‐IC did not react with normal donor platelets in the three techniques, in contrast to eluates from platelets sensitized with platelet antibodies.