bluuebunny/crossref_metadata_2025_split huggingface dataset:
B‐cell activation in human plasma cell dyscrasias
Authors: Levinson A. I. , Dziarski A. , Blankenhorn E. , Schreiber A. D. , Negendank W. G. 
Published: March 2008

SummaryWe studied the abnormal in vitro polyclonal B‐cell activity observed in patients with multiple myeloma and Waldenström's macroglobulinaemia. Numbers of cells spontaneously secreting immunoglobulin (Ig) in freshly isolated suspensions of peripheral blood mononuclear cells and pokeweed mitogen (PWM) stimulated cultures of blood mononuclear cells were determined with a protein. A reverse haemolytic plaque assay. These data were correlated with both the clinical and laboratory parameters of disease. Furthermore, Ig secreted into supernatants of PWM‐stimulated cultures was examined by a light chain radioimmunoassay for evidence of in vitro activation of malignant B‐cells. The mean level of circulating immunoglobulin secreting cells (IgSC) in patients was elevated when compared to that of normal subjects. The highest values were observed in those patients with the highest levels of serum paraprotein. However, experiments with cycloheximide suggested that such increased circulating IgSC values were often caused by the detection of Ig passively adsorbed to blood mononuclear cells. The studies with PWM stimulation of blood mononuclear cells were particularly revealing. Cultures of patient blood mononuclear cells with PWM showed depressed IgSC responses as a group compared to cultures of normal blood mononuclear cells: nevertheless, approximately half the patients demonstrated a sizeable response to PWM. No evidence for preferential activation of Ig secretion by the malignant B‐cell clone was observed. Impaired PWM induced responses were associated with advanced or progressive clinical disease.
Low‐dose cytosine arabinoside regimen induced a complete remission with normal karyotypes in a case with hypoplastic acute myeloid leukaemia with No. 8‐trisomy: in vitro and in vivo evidence for normal haematopoietic recovery
Authors: Tagawa M. , Shibata J. , Tomonaga M. , Amenomori T. , Yoshida Y. , Kuriyama K. , Matsuo T. , Sadamori N. , Ichimaru M. 
Published: March 2008

SummaryComplete remission was achieved in a case of hypoplastic acute myeloid leukaemia with chromosomal abberation of No. 8‐trisomy by giving very low dose of cytosine arabinoside (ara‐C), 10 mg (7.5 mg/m2)/d, by 24 h continuous intravenous infusion for 20 d. We observed a definite cytoreduction phase in the bone marrow (BM) before normal haematopoiesis resumed. The remission BM showed only normal karyotypes in all metaphases examined. Granulocyte/macrophage colonies and erythroid bursts recovered sufficiently in numbers and cytogenetic study on single colonies and bursts revealed only normal karyotypes. These observations provide evidence that a low dose ara‐C regimen can induce remission by cytoreduction which diverts the growth advantage from the leukaemic clone to the normal clones.
Cyclical neutropenia and T8 lymphocyte mediated stimulation of granulopoiesis
Authors: Smith J. G. , Seenan A. K. , Smith M. A. , Galloway E. , Lesko M. J. , Lucie N. P. , Robertson M. R. I. , Rowan R. M. 
Published: March 2008

SummaryA 33‐year‐old female with cyclical neutropenia and a reciprocally cycling T8 (suppressor/cytotoxic) lymphocytosis was investigated. T8 lymphocytes ranged between 1.4 and 5.6 × 109/1 and a significant proportion (50–75%) were preactivated (1a+). Fcy receptors were detected in only a minority (7–10%). Functional studies on the lymphocytes indicated that despite their phenotype, little natural killer and reduced suppressor activities were present. Anti‐granulocyte antibodies were not detectable in the serum.Production of colony stimulating activity (CSA) was assessed in the patient and control subjects’lymphocytes. Using a methylcellulose marrow culture system, the CSA production by the patient's lymphocytes was markedly increased compared with the control. Monoclonal antibody cytotoxic experiments confirmed that the T8 lymphocytes were responsible.As peaks of circulating T8 lymphocytes were synchronous with granulopoietic activity in the marrow, the above findings may represent a homeostatic mechanism which is attempting to compensate for an underlying stem cell defect.
The iron‐chelating agent picolinic acid enhances transferrin receptors expression in human erythroleukaemic cell lines
Authors: Testa U. , Louache F. , Titeux M. , Thomopoulos P. , Rochant H. 
Published: March 2008

SummaryPicolinic acid, a metal chelating molecule, was administered to human erythroleukaemic cell lines (K 562 and HEL) that were grown in serum‐containing media. Picolinic acid inhibited both iron uptake and cell growth. Furthermore, picolinic acid was shown to markedly decrease the level of ferritin in the cells. In spite of the inhibition of cell growth, picolinic acid induced a marked increase in the transferrin‐binding capacity of the cells. This phenomenon was due to a two‐fivefold enhancement of the rate of transferrin receptor biosynthesis. Other iron‐chelating compounds, capable of reducing the level of intracellular iron, also elicited a marked enhancement of the transferrin‐binding capacity of the cells. However, the addition of iron, as ferric ammonium citrate, in the culture medium elicited a marked increase in the level of ferritin and a strong decrease in the transferrin‐binding capacity of the cells. On the basis of these data we propose that a feed‐back mechanism is involved in the regulation of transferrin receptors: when the cells accumulate iron they decrease the number of transferrin receptors in order to prevent further accumulation of iron; when no or low iron is available to the cells, the number of transferrin receptors markedly increases as a compensatory mechanism.
Serum immunoreactive erythropoietin and erythropoiesis in protein‐energy malnutrition
Authors: Wickramasinghe S. N. , Cotes P. Mary , Gill D. S. , Tam R. C. , Grange Adenike , Akinyanju O. O. 
Published: March 2008

SummaryImmunoreactive erythropoietin was estimated in the sera of 23 Nigerian children with protein‐energy malnutrition (PEM) and 14 healthy Nigerian children of similar age attending a well baby clinic. The geometric mean estimate for this parameter was 262 mlU/ml (observed range 39–1340 mIU/ml; 95% confidence range 25–1738 mIU/ml) in the children with PEM and 80 mIU/ml (observed range 43–257 mIU/ml; 95% confidence range 27–241 mIU/ml) in the healthy children. Erythropoietin levels were above the 95% confidence range for the healthy children in 14 of the cases of PEM. There was a statistically significant inverse correlation between the haemoglobin levels of the children with PEM and the logarithm of immunoreactive serum erythropoietin estimates (r=–0.73; P<0.001). By contrast, statistically significant correlations were not found between the logarithm of erythropoietin estimates and either the percentage of erythroblasts in the marrow, the M/E ratio or the logarithm of the absolute blood reticulocyte count. These data suggest that there is no abnormality of erythropoietin production in PEM and that the anaemia seen in this condition results from an impairment of erythropoiesis. A stepwise multiple regression analysis revealed a positive correlation between the logarithm of the erythropoietin level and the logarithm of the concentration of circulating neutrophil metamyelocytes plus myelocytes and we speculate on the aetiology of this finding.
Absence of ABH antigens on neutrophils
Authors: Dunstan R. A. , Simpson M. B. , Borowitz M. 
Published: March 2008

SummaryMany investigators have concluded that polymorphonuclear leucocytes (PMN) express ABH antigens in parallel to red cells (RBC). We have examined human PMN for ABH antigens using human isoantibodies and mouse monoclonal antibodies with three highly sensitive and specific two‐stage assay systems: (1) fluorescence flow cytometry, (2) immunofluorescence microscopy, and (3) avidinbiotin immunoperoxidase microscopy. In all three assays the ABH antigens could not be detected on the surface of PMN. Previous reports alleging that ABH antigens occur on PMN probably represent false positive reactions due to inherent technical problems.
Deficient natural killer (NK) cells in paroxysmal nocturnal haemoglobinuria (PNH): studies of lymphoid cells fractionated by discontinuous density gradient centrifugation
Authors: Y oda Yasuhiro , Abe Tsukasa 
Published: March 2008

SummaryNon‐adherent, non‐B lymphoid cells from six patients with PNH and six healthy subjects were fractionated by Percoll discontinuous density gradient centrifugation (DDGC). The cell distribution pattern, NK cell activity (NKA), large granular lymphocytes (LGL) count and surface marker phenotypes were studied. The distribution patterns of patients’cells did not significantly differ from the controls. The peak of the NKA was found in low density fractions where the maximum counts of LGL, Leu‐7+ 2‐ cells and Leu‐11+ cells were present. The NKA and the proportion of Leu‐7+2‐ cells and Leu‐11+ cells were significantly lower in patients with PNH (P<0.001 for NKA and surface phenotypes; P<0.02 for LGL counts). NKA in the Percoll fractions was correlated with the counts of LGL (r= 0.69, P<0.001), Leu‐7+2‐ cells (r= 0.75, P<0.001) and Leu‐11+ cells (r= 0.89, P<0.001). Therefore, we concluded that NKA is deficient in PNH because of decreased NK cell counts.
DNA and RNA determination in 111 cases of childhood acute lymphoblastic leukaemia (ALL) by flow cytometry: correlation of FAB classification with DNA stemline and proliferation
Authors: Suarez Carlos , Miller Denis R. , Steinherz Peter G. , M elamed Myron M. , Andreeff Michael 
Published: March 2008

SummaryFlow cytometry with acridine orange was used in 111 cases of childhood acute lymphoblastic leukaemia (ALL) to determine simultaneously DNA index, cell cycle distribution and cellular RNA content in bone marrow samples. The overall incidence of DNA aneuploidy in the population was 40%. Significantly higher incidence of DNA aneuploidy was present in the L2 (70.6%) as compared to the L1 (34.1%) group (P= 0.007), using the FAB classification. No difference in the frequency of normal and abnormal DNA stemlines was found between newly diagnosed and relapsed patients. The L2 group had significantly higher proliferation (S phase = 12.4%) than L1 (S phase = 5.8%) (P=0.01), but RNA content was not significantly different. The aneuploid group had significantly more (P=0.01) cases with L2 morphology (28.6%) compared to the diploid group (8%) and proliferation was higher in DNA aneuploid (S‐phase = 9.5%) compared to DNA diploid (S‐phase = 4.7%) leukaemias. Likewise, RNA content was significantly higher in aneuploid than in diploid ALL (P= 0.006). These correlations between morphology, cell kinetics and DNA index elucidate biological properties of leukaemic cells with potentially prognostic value.
Interferon responses of peripheral blood mononuclear cells from normal and leukaemic children
Authors: Mohammed G. S. , Taylor C. E. , Dickinson A. M. , Craft A. W. , Kernahan J. , Reid M. M. , Proctor S. J. , Toms G. L. 
Published: March 2008

Summary. Human peripheral blood mononuclear cell cultures (PBMC) stimulated with Sendai virus or K562 cells produce a mixture of interferons. Temperature and pH stability characteristics and reactions with monospecific antibodies indicate that PBMC cultures from adults produce interferons alpha and gamma in approximately equal proportions. PBMC cultures from children produce lower levels of interferons with a higher proportion of type alpha.The ability of PBMC cultures from children with acute lymphoblastic leukaemia (ALL) to produce interferon was determined. Little or no gamma interferon was induced by either Sendai virus or K562 cells. Cultures from some children with ALL produced alpha interferon but mean levels were significantly lower than from normal children. A group of older children with ALL who had completed their course of therapy and were off treatment produced levels of interferon indistinguishable from those of normal children. This in vitro deficit, possibly induced by chemotherapy, may reflect an in vivo deficit and may contribute to the impaired handling of viruses seen in children being treated for ALL.
Reduced natural killer T‐cells in B‐cell chronic lymphocytic leukaemia identified by three monoclonal antibodies: Leu‐11, A10, AB8.28
Authors: Foa R. , Fierro M. T. , Lusso P. , Raspadori D. , Ferrando M. L. , Matera† L. , Malavasi F. , Lauria F. 
Published: March 2008

Summary. The proportion of E‐rosette positive T‐lymphocytes capable of reacting with three monoclonal antibodies (MoAbs)—Leu‐11, A10, AB8.28—‐ which appear to recognize specifically natural killer (NK) cells, was assessed in a series of untreated patients with B‐cell chronic lymphocytic leukaemia (B‐CLL). Irrespective of the clinical stage of the disease, the capacity of B‐CLL T‐lymphocytes to react with all three MoAbs was significantly reduced compared with that of normal circulating T‐cells (Leu‐11: 2·5%±1·9SD; A10: 2·3% 1·3; AB8.28: 7%±6·6 v Leu‐11: 13·5%±4·5; A10: 8·5%±4·6: AB8.28: 12% 5·5) Furthermore, a marked difference was demonstrated between the reactivity with the Leu‐11, A10, AB8.28 MoAbs and the proportion of Leu‐7 positive T‐cells, which in B‐CLL is significantly higher than in normal blood (23%±12·1 v 11·9%±5·9).These findings are in agreement with previous evidence of a discrepancy in B‐CLL between the phenotypic expression, assessed by Leu‐7 positivity, and the true functional activity of NK T‐cells, and suggest that the Leu‐11, A10 and AB8.28 MoAbs correlate well with the depressed NK function found in this disease.
Cellular levels of mRNA from c‐myc, c‐myb and c‐fes onc‐genes in normal myeloid anderythroid precursors of human bone marrow: an in situ hybridization study
Authors: Emilia Giovanni , Donelli Amedea , Ferrari Sergio , Torelli Umberto , Selleri Licia , Zucchini Patrizia , Moretti Luigi , Venturelli Donatella , Ceccherelli Giovanni , Torelli Giuseppe 
Published: March 2008

Summary. The expression of three onc‐genes, c‐myc, c‐myb and c‐fes, has been evaluated at the cellular level in myeloid and erythroid precursors of normal human bone marrow, by ‘in situ’ hybridization with tritium‐labelled probes. A relatively large amount of m‐RNA from the three onc‐genes was detected in myeloblasts and promyelocytes, but whereas the expression of c‐myb and c‐myb decreased in more advanced stage of maturation of the myeloid lineage, c‐fes mRNA remained at a relatively high level until the granulocyte stage, c‐myc and c‐myb were expressed at a fairly high level in basophilic erythroblasts, which also showed low levels of c‐fes mRNA. No expression of these onc‐genes was detectable in more mature erythroblasts, Megakaryocytes showed high levels of m‐RNA from all three onc‐genes.Our results suggest that c‐myc and c‐myb expression is related in some way to the cellular proliferation of myeloid and erythroid precursors, whereas c‐fes expression is more restricted to myeloid differentiation.
Blood cell phosphogluconolactonase: assay and properties
Authors: Beutler Ernest , Kuhl Wanda , Gelbart Terri 
Published: March 2008

Summary. 6‐Phosphogluconolactonase (6‐PGL) catalyses the second reaction of the hexosemonophosphate pathway. Although the ‐Iactone of 6‐phosphogluconic acid is the natural substrate for this enzyme, the more stable γ‐lactone may also be used. We prepared the γ‐lactone of 6‐phosphogluconic acid from 6‐phosphogluconate. When stored in dimethylsulfoxide, this material was found to be stable in liquid nitrogen for several months. A method for measuring 6‐phosphogluconolactonase (6‐PGL) using the γ‐lactone as substrate has been developed, after defining conditions under which spontaneous hydrolysis of the lactone is relatively slow and the enzymatic velocity is relatively rapid.The enzyme had no divalent cation requirement and was not significantly inhibited by a 50‐fold excess of gluconolactone. It was distinct, therefore, from gluconolactonase. At 25C normal human red cells were found to contain approximately 50 IU of 6‐phosphogluconolactonase/g Hb. The activity of the enzyme was independent of red cell age. Based on protein content, human lymphocytes, monocytes, granulocytes and platelets, contained approximately 10 times the activity of red blood cells. The activity of 6‐PGL was stable for at least 6 d in red cells stored at 22C and for at least 20 d in red cells stored at 4C.
Coated pit formation: a membrane function involved in the regulation of cellular iron uptake
Authors: Egyed A. , Fodor I. , Lelkes G. 
Published: March 2008

Summary. Diferric‐transferrin induces a marked increase in the number of coated pits on the reticulocyte membrane. This increase is followed by a decline, often to below the initial number. Since a good correlation was found between the rate of iron uptake and the number of coated pits, but not between the rate of transferrin recycling and the coated pit count, it is likely that coated pit formation is necessary for the removal of iron from transferrin.The decline in the number of transferrin‐induced coated pits was observed only when haem synthesis was undisturbed, indicating that the accumulation of intracellular haem inhibits coated pit formation.Based on these results we suggest that haem regulates the rate of iron uptake by inhibiting iron removal rather than receptor recycling.
GγAγ(δβ)°‐thalassaemia and a new form of γ globin gene triplication identified in the Yugoslavian population
Authors: Efremov G. D. , Filifcče V. , Gjorgovski I. , Juričič D. , Stojanovski N. , Harano T. , Nakatsuji T. , Kutlar A. , Kutlar F. , Bakioglu I. , Huisman T. H. J. 
Published: March 2008

SummaryAmong several hundred apparently healthy Yugoslavian adults with slightly elevated levels of fetal haemoglobin, we have identified two distinct abnormalities, (a) A GγAγ(δβ)°‐thalassaemia heterozygosity with an ∼ 15 kb deletion which involves part of the δ globin gene and the β globin gene. This deletion is probably the same as that seen among Italians (Ottolenghi et al, 1982; Carèet al, 1984). (b) A nondeletion form of hereditary persistence of Hb F which is caused by a γ globin gene triplication of the (+)Gγ mD (+)Gγ mD Aγ type. It is characterized by the presence of some 5% Hb F in the heterozygote containing nearly 100%Gγ chains. The C→T mutation at position — 158 5’to the Gγ chain [(+)Gγ], identified through analyses of Xmn I digests, was present at both Gγ globin genes. This mutation is known to be associated with increased Gγ chain production (Gilman & Huisman, 1985), and thus is responsible for the increased Gγ chain production in these heterozygotes. The condition is different from the (+)Gγ mD (+)Gγ nondeletion type of HPFH which has been observed in heterozygotes of two Black families, and is associated with the presence of 3–4% Hb F (with mainly Gγ chains) in heterozygotes.
Pure red cell aplasia: lymphocyte inhibition of erythropoiesis
Authors: Abkowitz Jamis L. , Kadin Marshall E. , Powell Jerry S. , Adamson John W. 
Published: March 2008

SummaryThe pathogenesis of pure red cell aplasia (PRCA) was studied in a patient who had no evidence of malignancy. In marrow culture, no erythroid colonies (from late erythroid progenitors [CFU‐E]) but normal numbers of well‐haemoglobinized erythroid bursts (from early erythroid progenitors [BFU‐E]) were found, indicating that BFU‐E existed in the patient but that their subsequent in vivo differentiation was inhibited. Autologous coculture studies suggested that inhibition was mediated by the patient's ER+ lymphocytes. After remission was induced with cyclophosphamide, autologous ER + cells no longer suppressed in vitro erythropoiesis. However, cryopreserved ER + cells, obtained with anaemia, suppressed BFU‐E growth from remission marrow. An expanded population of large granular lymphocytes (LGL) with ER +, Fcγ+. T3 +, T8 +, HNK‐1 +, Ia —, M1 — phenotype and no functional natural killer (NK) cell activity was noted during PRCA that reverted to normal with remission. For this patient, both in vivo and in vitro evidence demonstrates a cellular inhibition of erythropoiesis at the level of differentiation between BFU‐E and CFU‐E.
Chronic idiopathic and secondary neutropenia: clinical and serological investigations
Authors: Van der Veen J. P. W. , Hack C. E. , Engelfriet C. P. , Pegels J. G. , Kr. vondem Borne A. E. G. 
Published: March 2008

SummaryClinical data on 49 patients with chronic idopathic neutropenia (CIN) and 42 patients with neutropenia secondary to a well‐defined immuno‐logical disorder (SN) were collected and related to serological parameters. In 47% of the patients with CIN and 53% of those with SN, a positive direct immunofluorescence test was obtained with granulocytes from the patients. In the sera from the patients in the two groups, antibodies against donor granulocytes were detected by the indirect immunofluorescence test, the leucoagglutination test and/or the granulocytotoxicity test in 15%, 19% and 15%, respectively. The results of the above tests could not be correlated with any clinical or haematological parameter.
Adult‘fetal‐like’erythropoiesis characterizes recovery from bone marrow transplantation
Authors: Weinberg R. S. , Schofield J. M. , Lenes A. L. , Brochstein J. , Alter B. P. 
Published: March 2008

SummaryThe transient fetal‐like erythropoiesis which appears during recovery from bone marrow transplantation has now been examined at the level of erythroid progenitor cells. A 7‐year‐old boy with β+‐thalassaemia major was studied during engraftment from his β‐thalassaemia trait sister. Hb F and i antigen rose as expected. Macrocytosis never developed, but red cell size distribution became very heterogeneous. Bone marrow CFU‐E and BFU‐E were detected by 30 d, prior to the appearance of reticulocytes. Marrow erythroid progenitor cell numbers were normal by 146 d, while those in the blood became normal by 360 d. After transplantation globin synthesis ratios in erythroid colonies were diagnostic of thalassaemia trait, indicating engraftment. Individual erythroid colonies derived from both blood and marrow at all times during reconstitution showed no correlation of Gγ and γ. Thus the fetal‐like stress erythropoiesis of marrow expansion following transplantation was derived from adult and not fetal progenitor cells.
Thrombocytopenia associated with gold therapy: a drug‐induced autoimmune disease?
Authors: Kr. Von Dem Borne A. E. G. , Pegels J. G. , Van Der Stadt R. J. , Van Der Plas‐Van Dalen C. M. , Helmerhorst F. M. 
Published: March 2008

SummaryWe studied 13 patients with rheumatoid arthritis (RA) and gold‐induced thrombocytopenia. Platelet‐specific autoantibodies of the IgG and often also of the IgM class were detected by immunofluorescence on the patient's platelets and in ether eluates from these platelets. In nine patients we also detected autoantibodies in the serum. The antibodies were unreactive with platelets from patients with Glanzmann's disease in most cases, and were not EDTA dependent. Thus, they had the serological characteristics of true autoantibodies. The reaction of the antibodies with platelets was not influenced by the addition of extra gold. By atomic absorption spectrophotometry we found that the ether eluates, which were often strongly reactive with donor platelets, were free of gold. This indicated that the autoantibodies in the thrombocyto‐penic patients were not dependent on gold for their reaction. The possibility is raised that gold treatment of rheumatoid arthritis patients induces or enhances the formation of platelet‐specific autoantibodies, and that gold‐induced thrombocytopenia is a drug‐induced autoimmune disease.