bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative study of eosinophil purification on Nycodenz, Metrizamide and Percoll density gradients
Authors: Brattig N. W. , De la Garza C. E. Medina‐ , Tischendorf F. W.
Published: July 2010

Studies on the metabolism of human eosinophils and their interaction with helminthic parasites have been hampered by the difficulty in obtaining these granulocytes in sufficient purity and quantity. In this report, we describe for the first time the application of the density medium Nycodenz for the purification of eosinophils from peripheral blood. Nycodenz density gradient centrifugation is compared with Percoll and Metrizamide gradient centrifugation with special emphasis on cell yield, purity of cell suspensions, and functional integrity of separated cells. Percoll gradients provide purer preparations (mean value 94 ± 15%) of eosinophils from blood with moderate eosinophilia than Nycodenz or Metrizamide (58 ± 29 and 88 ± 13%, respectively). The recovery rates of eosinophil‐enriched fractions were low after Nycodenz centrifugation (29 ± 19%) in comparison to Metrizamide (60 ± 21%) or Percoll (70 ± 16%). Eosinophils (as neutrophils), prepared by the 3 techniques, function metabolically (superoxide anion generation) and in assays measuring phagocytosis (S. aureus, zymosan particles). Percoll gradient isolated eosinophils (as neutrophils) adhere to and immobilize larvae of Onchocerca volvulus.
Platelet glucose metabolism in Type I diabetic subjects
Authors: Leoncini G. , Maresca M. , Balestrero F. , Polvani C. , Arrnani U. , Piana A.
Published: July 2010

In a group of 35 type I diabetics, platelet glycolytic and glycogenolytic flux have been measured. In type I diabetic platelets glucose uptake was significantly reduced. The quite normal lactate production was obtained by a faster utilization of stored glycogen in these patients. Specific activity of glycolytic enzymes was normal, in particular the levels and kinetic properties of soluble and membrane bound hexokinase. The rate of glucose flux through the hexose monophosphate shunt, measured either in resting or in arachidonic acid‐stimulated platelets, was normal in diabetics. Kinetics of glucose transport across plasma membrane have also been determined. Km was significantly increased in diabetic patients. No changes was shown in Vmax. Modifications present in membrane organization of patients could involve glucose transport protein.
Specific binding of B‐CLL cell‐derived chemokinetic inhibitory factor (CIF) to human polymorphonuclear leukocytes
Authors: Siegbahn Agneta , Garcia Rodolfo C. , Kishi Kenji , Nilsson Kenneth , Venge Per
Published: July 2010

The chemokinetic inhibitory factor (CIF) is a recently described B‐cell derived lympho‐kine that mediates a chemokinetic inhibitory effect on human polymorphonuclear leukocyte (PMN) migration. In the present report the interaction of CIF with the neutrophil plasma membrane was studied. Normal human peripheral blood neu‐trophils and purified neutrophil plasma membranes selectively removed biologic activity from CIF‐containing concentrates obtained during the purification procedure from conditioned medium. Removal was obtained at both 4°C and 37°C. Furthermore, HL‐60 cells treated with dimethyl sulfoxide removed CIF activity (granulocyte‐like cells) but HL‐60 cells treated with 12–0‐tetradecanoylphorbol‐13‐acetate (ma‐crophage‐like cells) did not. Purified human blood monocytes, cells from the mac‐rophage‐like U‐937 cell line and cells from the basophilic leukemia cell line KU‐812 did not remove CIF. These studies suggest that neutrophils express specific binding sites for CIF‐activity.
A case of Bernard‐Soulier syndrome: Study of platelet glycoprotein Ib in a kindred
Authors: Ingerslev J. , Stenbjerg S. , Taaning E.
Published: July 2010

The Bernard‐Soulier syndrome is characterized by low platelet counts, abnormally large (giant) platelets, and impaired or absent platelet aggregation by the inducer antibiotic ristocetin. The recent discovery of the inherited biochemical defect and the deficient synthesis of platelet glycoprotein Ib (GP‐Ib), has contributed greatly to the understanding of the disease. We report a case of the Bernard‐Soulier syndrome presenting with bleeding from the pharynx after adenotomy. The patient and nearest family members were studied by a novel immunoperoxidase method for quantification of platelet glycoprotein Ib using a specific monoclonal antibody (AN51).
HIV infection due to a platelet transfusion after allogeneic bone marrow transplantation
Authors: Apperley J. F. , Rice S. J. , Hewitt P. , Rombos Y. , Barbara J. , Gabriel F. G. , Goldman J. M.
Published: July 2010

A 30‐yr‐old man with chronic granulocytic leukaemia received a bone marrow transplant from his histocompatible sister in December 1982. His post‐transplant course was complicated by Grade III graft‐versus‐host disease and multiple infectious episodes until his death from pneumonia on d +190. He was later found to be seropositive for anti‐HIV at the time of his death. Retrospective analysis of stored sera showed a transient period of seropositivity from d +11 to d +20 thought to reflect passive transfer of antibody from a blood product transfused prior to d +11 when he was also exposed to infectious virus. He remained seronegative until d + 78 when anti‐HIV was again found. Seropositivity persisted until his death and was attributed to endogenous antibody response. Although it is unclear whether his clinical course was due to AIDS, exposure of an immunosuppressed patient to HIV may be associated with more rapid development of clinical disease.
The treatment of adult idiopathic thrombocytopenic purpura
Authors: Simon Marc , Jouet Jean‐Pierre , Fenaux Pierre , Pollet Jean‐Paul , Walter Marie‐Pierre , Bauters Francis
Published: July 2010

16 adult idiopathic thrombocytopenic purpura (ITP) patients, with mean age 51 years, were treated by 5 weekly slow intravenous infusions of vinblastine (0.1 mg/kg). When a complete or partial response (CR or PR) was obtained, slow infusions were repeated at 2‐weekly then monthly intervals, as maintenance therapy. In 4 cases with ITP of recent onset, but presenting contraindication or failure to prednisone and high dose intravenous immunoglobulins, CR was obtained in all patients after 4 to 15 days (mean 9.5). Only one of these patients relapsed. In 12 cases of refractory chronic ITP (of whom 10 had been splenectomized), there were 2 CR, 6 PR and 4 failures. The 8 responding patients had a mean interval to response of 20 days. The 6 PR were short and did not exceed 15 days. Our results do not support a superiority of this treatment compared to other modes of administration of vinca alkaloids in ITP (intravenous bolus, vinca loaded platelets).
Inhibitory effect of peak 2–4 of uremic middle molecules on platelet aggregation
Authors: Palés J. L. , Asensio A. , Merola E. , Company X. , Deulofeu R. , Garcia M. , Balagué A. , López A.
Published: July 2010

It is well‐known that uremic patients present prolonged bleeding times as a common complication. Factors responsible for this disorder have been extensively investigated. In order to elucidate the possible role of uremic middle molecules as responsible for the bleeding tendency observed in uremia, we have studied the effect on platelet aggregation of middle molecules obtained from uremic plasma by Sephadex and ionexchange chromatography. Our results show that some purified middle molecular fractions have a specific inhibitory activity on platelet aggregation and suggest an important role for these compounds in the pathogenesis of uremic bleeding.
Potential value of vintristine‐adriamycin‐dexamethasone combination chemotherapy (VAD) in refractory and rapidly progressive myeloma
Authors: Collin R. , Greaves M. , Preston F. E.
Published: July 2010

10 patients with myeloma refractory to alkylating agents were treated with either 4‐d pulses of high‐dose dexamethasone therapy, or 4‐d pulsed high‐dose dexamethasone in combination with 4‐d continuous infusions of vincristine and adriamycin (VAD). 8 patients were evaluated after a median duration of treatment of 2.3 courses (range 1 to 4). 6 of the 8 evaluable patients achieved reduction in serum and/or urine paraprotein levels with a mean reduction in serum paraprotein of 74.1%. There was a concomitant improvement in wellbeing in these responding patients. 2 evaluable patients failed to show biochemical or clinical response (1 treated with VAD, 1 high‐dose dexamethasone). 2 patients currently survive 390 d and 180 d, respectively, on continuing therapy. 8 patients died with a mean duration of survival of 99 d (range 10 to 246 d). We conclude that the use of VAD chemotherapy in patients with refractory myeloma confers both a worthwile remission of disease symptoms and biochemical evidence of disease regression, and that trials of VAD as primary treatment for myeloma are indicated.
Polyclonal B‐cell activation after intravenous immunoglobulin therapy in idiopathic thrombocytopenic purpura — an anti‐idiotype response?
Authors: Wangel A. G. , Lorenzetti M. , Pettersson T.
Published: July 2010

Polyclonal B cell activation occurred in 3 patients following treatment with intravenous immunoglobulin (i.v. Ig) for idiopathic thrombocytopenic purpura (ITP). The possibility that this may represent an anti‐idiotype response and the hypothesis that prolonged remission of ITP may be induced by this mechanism are discussed.
Enrichment of blood units with young red cells (neocytes) with the IBM 2991 cell washer
Authors: Picot C. , Girot R. , Loutounda J. , Mattlinger B. , Maier‐Redelsperger M. , Feo C. , Chevalier A. , Barritault L.
Published: July 2010

The transfusion of young red blood cells (neocytes) is a complementary approach to the present treatment of thalassaemia major patients. Fresh neocytes were harvested from 34 volunteers with the IBM 2991 cell washer (CW). The upper part of 24 units was separated into 6 aliquots (T1‐T6) of 15 ml each and the residue homogenized. Four biological criteria were used to evaluate young red cell quality, the erythrocyte pyruvate kinase activity, the mean corpuscular volume, the reticulocyte count and ektacytometry; each sample (T1‐T6) showed an enrichment with neocytes as compared with the standard unit. A real efficiency of this technique with the IBM 2991 CW was obtained with the first third of the unit, corresponding to the T1‐T4 fractions. The estimation of the theoretical mean life span of T1‐T2 was 270 days. The last 10 units were separated into two halves: the enrichment of the first half was worse than in the first third of the previous technique. We concluded that the transfusional program of thalassaemia patients could profit by the use of the most enriched part of a standard blood unit with the IBM 2991 CW.
Effect of 32P treatment for polycythaemia vera on blood lymphocyte subpopulations and their functions
Authors: Petrini B. , Blomgren H. , Wasserman J. , Svedmyr E. , Stedingk L. V. , Schnell P. O.
Published: July 2010

The influence of 12P treatment on the blood lymphocyte population was examined in 16 patients with polycythaemia vera who had not previously been treated with cytotoxic drugs or irradiation. Before treatment the lymphocyte counts were within the normal range but the expression of certain membrane structures, as detected by monoclonal antibodies directed against total T cells (CD 3 and 5), helper/inducer (CD 4) and suppressor/cytotoxic T cells (CD 8), were slightly reduced. In addition, mitogenic responses of the lymphocytes to PHA and PWM‐induced Ig secretion were severely impaired. Following a single oral dose of 32P (150–305 MBq), which was shown to normalize the production of erythrocytes and/or platelets, the blood lymphocyte counts were reduced by approximately 40% 12 wk after treatment. Subset analysis showed that the proportion of B cells, as identified by monoclonal antibodies (CD 20), was reduced to the highest relative extent. On the other hand, lymphocytes expressing the above T cell markers were somewhat increased. 32P treatment sharply increased PHA reactivity but it further reduced PWM‐induced Ig secretion. The latter observation was in line with the finding that serum concentrations of Ig were reduced following treatment.
Alpha interferon in the treatment of symptomatic myelofibrosis with myeloid metaplasia
Authors: Parmeggiani L. , Ferrant A. , Rodhain J. , Michaux J. L. , Sokal G.
Published: July 2010

2 patients with myelofibrosis and myeloid metaplasia had symptomatic splenomegaly and were treated with interferon alpha‐2c (IFN alpha‐2c). The splenic pain and pressure symptoms disappeared, accompanied by a decrease in the size of the spleen. However, the peripheral blood count worsened and no improvement in the bone marrow fibrosis could be observed.
Adult T‐cell leukemia following long‐term remission from non‐Hodgkin's lymphoma
Authors: Yonekura Shuji , Nagao Tadami , Komatsuda Mitsumoto , Arimori Shigeru
Published: July 2010

A female patient who had been initially diagnosed with non‐Hodgkin's lymphoma (NHL) and achieved complete clinical remission with combined chemotherapy, developed overt adult T‐cell leukemia (ATL) after 9 yr of disease‐free survival. This is the first case of the development of ATL following the complete remission of NHL. Secondary malignant neoplasms are not well‐documented in patients previously diagnosed with Hodgkin's disease. Although there have been a few reports concerning the occurrence of secondary malginancy in patients with non‐Hodgkin's lymphoma (NHL), there has never been a documented case of ATL following long‐term survival from NHL. Here, we report a case of typical adult T‐cell leukemia (ATL) which occurred after 9 yr disease‐free survival from NHL.
Correlation between bone marrow karyotype and the occurrence of erythroblast micronuclei and nuclear budding in patients with myelodysplastic syndromes
Authors: Teerenhovi L. , Lintula R. , Ruutu T. , Knuutila S.
Published: July 2010

147 patients with myelodysplastic syndromes were investigated for the presence of micronuclei and nuclear budding in bone marrow erythroblasts. The patients were divided into subgroups on the basis of bone marrow karyotype. 31 healthy bone marrow donors constituted a control group. Patients with monosomy 7 or 7q‐ and patients with major karyotypic abnormalities (MAKA) had significantly more erythroblasts with micronuclei and nuclear budding than the control group. Patients with a 5q‐ chromosome as the sole karyotypic aberration had more micronuclei than the controls. For other patients with MDS the differences were statistically nonsignificant.
Staging and treatment of non‐Hodgkin's lymphoma of intermediate‐grade malignancy: A retrospectective study of 102 cases
Authors: Schaafsma M. R. , Bieger R. , Hermans J. , Kluin Ph. M. , Noordijk E. M. , Willemze E R.
Published: July 2010

Since the introduction of the Working Formulation for Clinical Usage, 3 different prognostic groups are recognized among the various histological classifications of non‐Hodgkin's lymphomas. We looked at the lymphomas of intermediate‐grade malignancy and studied retrospectively the staging and treatment of 102 patients. Almost half of the patients with clinical stage I disease, who therefore received radiotherapy only, later appeared to have had more extended disease. For patients with stage II, III and IV disease the complete remission rate was significantly higher with CHOP than with CVP (76% versus 36%). However, once complete remission was achieved there was no difference in disease‐free survival between the 2 groups (at 4 yr, 50% of the patients were in complete remission). As far as the amount of cytostatic drugs given during the initial courses of chemotherapy is concerned, no difference was found between patients who achieved complete remission and those who did not. Most patients did not receive the full dosage. For those patients who did not respond well to initial therapy, or who suffered a relapse, second line therapy was disappointing.
A synthetic hemoregulatory peptide (HP5B) inhibits human myelopoietic colony formation (CFU‐GM) but not leukocyte phagocytosis in vitro
Authors: Laerum Ole Didrik , Sletvold Olav , Bjerknes Robert , Paukovits Walter R.
Published: July 2010

A synthetic analog of a hemoregulatory peptide associated with mature human granulocyte (HP5B) has been investigated for inhibitory effects on human myelopoietic stem cells in vitro. In addition, it has been tested for effects on phagocytosis by human granulocytes and monocytes by use of an automatic flow cytometric method. A dose‐dependent inhibition of colony formation was found after preincubation of bone marrow cells for 1 h at 37°C in the range 10−7‐10−11 mol/l. Above or below these concentrations, no inhibitory effects were seen. The degree of inhibition varied from experiment to experiment, indicating variable responsiveness of the donor cells. Maximal effect was of magnitude 90% inhibition, and the optimal dose was 10−7 mol/l. The peptide had no effect on the kinetics of phagocytosis by measurements of the uptake of fluorescent Zymosan particles or Staphylococcus aureus. This may indicate a selective effect on the precursor cells, with no effect on the functional state of their progeny, the granulocytes and monocytes.
Effects of hypoxia on megakaryocytopoiesis and granulopoiesis
Authors: Petursson Sigurdur R. , Chervenick Paul A.
Published: July 2010

Previous studies have reported that exposure of mice to hypoxic conditions results in a decrease in blood platelets. To further explore the effect of hypoxia on megakaryocytopoiesis, megakaryocytes and their progenitor cells (CFU‐M) were studied in hypoxic mice. Mice were exposed to hypoxia by enclosure in cages covered with dimethyl‐silicone rubber membranes for up to 10 d. At various times during the hypoxic and ex‐hypoxic periods the total megakaryocytes and CFU‐M were determined in the humerus and spleen. CFU‐M were assayed in the soft gel colony forming assay using pokeweed mitogen‐stimulated spleen cell conditioned medium (PWCM) as a source of colony stimulating activity. After 10 d of hypoxia, packed red cell volume (PRCV) increased to 148% of control levels and blood platelets decreased to 40% of controls. Total megakaryocytes and CFU‐M per humerus decreased to 18% and 50% of controls respectively. 4 d into the ex‐hypoxic phase, PRCV was still increased at 128% of controls while marrow megakaryocytes and CFU‐M increased to normal levels. Platelet recovery was somewhat slower, returning to normal by d 6. In contrast to the findings in the marrow, total spleen megakaryocytes and CFU‐M increased to about 3‐ and 5‐fold of control levels respectively by 6 d of hypoxia. During the exhypoxic phase, CFU‐M decreased to normal on d 4, followed by a rebound of 3‐fold control values on d 8. Spleen megakaryocytes decreased more slowly, returning to normal by d 10. A marked granulocytosis was observed during the hypoxic phase. Changes in granulocytes and granulocyte‐macrophage progenitor cells (CFU‐GM) in marrow and spleen were similar to those observed for megakaryocytes and CFU‐M. The results indicate that the thrombocytopenia of hypoxia is due to a decrease in production of marrow megakaryocytes and CFU‐M and is not offset by a simultaneous increase in spleen megakaryocytopoiesis.
Impaired heme synthesis in a family with Pelger‐Huët anomaly, recurrent abdominal pain attacks and impaired neutrophil motility in vitro
Authors: Pasanen Aarne V. , Ruutu Petri , Kosunen Timo U. , Tenhunen Raimo
Published: July 2010

Heme synthesis was studied by measuring the activity of δ‐aminolevulinic acid synthase (AmLev synthase) in granulocytes, the activity of δ‐aminolevulinic acid dehydratase (AmLev dehydratase) and of uroporphyrinogen I synthase in erythrocytes as well as the concentrations of coproporphyrin and protoporphyrin in erythrocytes of 6 patients with Pelger‐Huët anomaly. 3 of these patients from the same kindred had a syndrome of recurrent attacks of fever and abdominal pains, a tendency to skin infections, delayed wound healing and impaired neutrophil motility. The other 3 patients were asymptomatic. The activity of AmLev synthase was depressed in all 3 symptomatic patients and normal in the asymptomatic patients. 1 symptomatic patient had a decreased erythrocyte protoporphyrin concentration. These findings indicate a derangement of heme synthesis in the symptomatic patients. Their abdominal pain attacks could be due to heme depletion. The findings suggest that the abdominal pains of patients with porphyria could be due to decreased heme synthesis rather than due to accumulation of porphyrin precursors in tissues. The cause of the impaired neutrophil motility may be a defect in energy metabolism due to decreased supply of heme for oxidative metabolism.
Successful oral chemotherapy with idarubicin in refractory anaemia with excess blasts
Authors: Johnson E. , Parapia L. A.
Published: July 2010

6 patients with refractory anaemia with excess blasts (RAEB) were treated with a new oral anthracycline, idarubicin. 3 patients achieved complete remission, and the remaining 3 achieved partial remission. These responses were maintained for 8–60 wk, the longer durations being in the patients who achieved complete remission. Treatment was given on an outpatient basis, and all but 1 patient remained at home for most of the disease course. Unwanted effects were mild. It would thus appear that oral idarubicin is an effective treatment for RAEB, in addition to allowing outpatient management. Larger studies are required for futher evaluation.
A first case of complete remission of β‐interferon sensitive adult T‐cell leukemia
Authors: Matsushima M. , Yoneyama A. , Nakamura T. , Higashihara M. , Yatomi Y. , Tanabe A. , Ohashi T. , Oka H. , Nakahara K.
Published: July 2010

A case of complete remission of adult T‐cell leukemia (ATL) induced by β‐interferon is reported. A 46‐year‐old male was diagnosed as ATL because of the increased number of ATL cells with deeply indented and lobulated nuclei in the peripheral blood, accompanied by elevated values of the lactic dehydrogenase, the alkaline phosphatase, and the calcium in the serum. The result of the cell surface marker analysis of peripheral blood lymphocytes was compatible with ATL and anti‐ATL associated antibody (ATLA) was positive. The integration of proviral deoxyribonucleic acid (DNA) of human T‐cell leukemia virus type I(HTLV‐I) was proved in the peripheral blood lymphocytes using Southern blot hybridization. Since an ordinal chemotherapy was not so effective for this patient, he was treated with 1.8 times 107 units of recombinant β‐interferon (β‐IFN) per day for 7 days as one course. After 5 courses of treatment, a markedly favorable response was recognized, and he achieved complete remission. A lower dose of β‐IFN (9 times 106 units per day for 3 days as one course, one or two courses per month) has been continued and he has still been in a complete remission state for 10 months. It is concluded that β‐IFN should be used to treat ATL.
Cytogenetic and immunologic characterization of mitotic cells in chronic lymphocytic leukaemia
Authors: Autio K. , Elonen E. , Teerenhovi L. , Knuutila S.
Published: July 2010

Lymphocytes from 14 patients with chronic B‐cell leukaemia (B‐CLL) and one with chronic T‐cell leukaemia (T‐CLL) were studied by the MAC (Morphology, Antibodies, Chromosomes) method, which allows simultaneous analysis of the morphology, immunologic phenotype and karyotype of the same mitotic cell. Use of the MAC‐method in present studies has yielded new information about the cytogenetics of CLL. Although most of the interphase cells from patients with B‐CLL were positive for B‐cell markers, many of the mitotic cells turned out to be T cells, supporting the notion that the cells studied by conventional chromosome analysis are often non‐neoplastic T cells. In some B‐CLL cases with normal karyotype in the conventional chromosome study, however, most of the mitotic cells were B cells, indicating that neoplastic B cells may also have a normal karyotype. The patient with T‐CLL had normal karyotype even though most of the mitoses were T cells. The chromosome abnormalities found were restricted to cells with light chain clonality. Our results show that clonal chromosome abnormalities do occur in neoplastic B cells of patients with B‐CLL.
Granular common acute lymphoblastic leukaemia in adults: A morphological study
Authors: Hay C. R. M. , Barnett D. , James V. , Woodcock B. W. , Brown M. J. , Lawrence A. C. K.
Published: July 2010

2 cases of acute lymphoblastic leukaemia characterised by the presence of cytoplasmic inclusions morphologically similar to azurophil granules are described. Azurophil granulation of blasts is one of the cardinal features which differentiate acute myeloid from acute lymphoblastic leukaemia. Although such granulation of lymphoblasts has caused diagnostic confusion in the past, we found that the granules could be distinguished from myeloid azurophil granules both morphologically and by their characteristic cytochemical staining reactions. They were negative for peroxidase/sudan black and chloroacetate esterase, but gave coarse scattered granular positivity for both acid phosphatase and alpha‐naphthyl acetate esterase. Both the electron microscopic appearance of the granules and their cytochemical staining reactions suggested that they were lysosomes. Granular ALL does not appear to be associated with any morphological subtype or karyotype; but is strongly associated with the common ALL phenotype. Its prognostic significance remains uncertain. It occurs more frequently than the small number of previous reports might suggest and, given the potential for misdiagnosis, should be more widely recognised.
Abnormality of platelet size and T‐lymphocyte proliferation in an autosomal recessive form of dyskeratosis congenita
Authors: Juneja H. S. , Elder F. F. B. , Gardner F. H.
Published: July 2010

Dyskeratosis congenita (DC) is a rare familial hematologic disorder that has various modes of inheritance. We have studied 2 siblings with DC. 1 sibling had thrombocytopenia, which responded to therapy with nandrolone decanoate and oxymetholone. Platelets were abnormally small, which indicates that a qualitatively abnormal megakaryocytopoiesis is a feature of DC. Myeloid and erythroid progenitors in specimens of the blood and bone marrow from both siblings were either absent or greatly reduced in numbers. The qualitatively abnormal megakaryocytopoiesis, and the quantitative abnormality of hematopoietic progenitor cells committed to myelopoiesis and erythropoiesis, indicates involvement of the pluripotent stem cell in DC. Cytogenetic studies of the bone marrow and peripheral blood lymphocytes from these patients showed normal karyotypes, a normal sister chromatid exchange frequency, and a rapid proliferation of peripheral T lymphocytes, a feature of the disorder that has not been reported previously.
B‐cell chronic lymphocytic leukaemia with aberrant expression of CD8 antigen
Authors: Porwit A. , Borgonovo L. , ösby E. , Lenkei R. , Smith C. I. E. , Hammarström L.
Published: July 2010

The monoclonal antibodies against CD8 (T suppressor/cytotoxic) antigen (Leu2/OKT8) were found to bind to leukaemic lymphocytes from a patient with chronic lymphocytic leukaemia. The cells also had an unusual type of rod‐like cytoplasmic immunoglobulin of IgM/γ type as seen by light, fluorescence and electron microscopy, and displayed several antigens characteristic for B lymphocytes. Gene rearrangement analysis showed rearrangement of μ heavy chain gene. In spite of an expression of CD8 antigen, T‐cell receptor genes were not rearranged.
Variation in iron accumulation, transferrin membrane binding and DNA synthesis in the K‐562 and U‐937 cell lines induced by chelators and their iron complexes
Authors: Forsbeck Klas , Nilsson Kenneth , Kontoghiorghes George J.
Published: July 2010

Eight chelators – 8‐hydroxyquinoline, 1‐hydroxypyridine‐2‐thione (omadine), tropolone, pyridoxal isonicotinoyl hydrazone, 2‐methyl‐3‐hydroxypyr‐4‐one (maltol), 1‐methyl‐3‐hydroxypyrid‐2‐one, 1,2‐dimethyl‐3‐hydroxypyrid‐4‐one and mimosine – and their iron complexes were tested on cells of the established human tumour cell lines K‐562 (erythroleukaemic) and U‐937 (monoblastoid) for their effects on a) cellular accumulation of iron provided by transferrin (Tf) via receptor‐mediated endocytosis, b) specific cell surface binding of Tf, c) cell viability and, d) DNA synthesis. The lipophilic chelators suppressed the accumulation of Tf‐supplied iron in the K‐562 cells and less so in the U‐937 cells, whereas the effects of the other chelators were closer to control range. The lipophilic chelators pyridoxal isonicotinoyl hydrazone, tropolone, 8‐hydroxyquinoline and omadine were found to be cytotoxic in this order, with the U‐937 being generally more sensitive than K‐562. The presence of iron diminished the toxicity. The DNA synthesis was also affected, from a partial suppression in K‐562 to a slight increase in U‐937 in the presence of pyridoxal isonicotinoyl hydrazone and to strong suppression with 8‐hydroxyquinoline and omadine. Addition of iron partially reversed the inhibition. The other chelators had low cytotoxic effects that disappeared upon iron saturation. Maltol, particularly in the absence of iron, 1,2‐dimethyl‐3‐hydroxypyrid‐4‐one and 1‐methyl‐3‐hydroxypyrid‐2‐one supported DNA synthesis. Long‐term culturing (24 h) of both cell types in the presence of the non‐cytotoxic chelators resulted in increased specific Tf binding, which was interpreted as the result of an increased Tf‐receptor synthesis. This is presumably triggered via the chelators' interaction with a certain cellular iron pool.
Specificity of haematological indicators for ‘5q‐ syndrome’ in patients with myelodysplastic syndromes
Authors: Teerenhovi L.
Published: July 2010

83 patients with myelodysplastic syndromes were analyzed for the presence of three haematological features: (1) macrocytic anaemia, (2) normal or high platelet count and (3) megakaryocytic hypolobulation in most megakaryocytes. In 10 of the 83 patients, a 5q‐ chromosome was the the only clonal aberration; 31 patients had other chromosomal aberrations (including 6 patients with 5q‐ chromosome and other abnormalities in the same clone) and 42 patients had a normal karyotype in their bone marrow cells. 9 patients displayed all three haematological features investigated. In 8 of these patients the 5q‐ chromosome was the only clonal aberration. The 9th patient had a karyotype of 47,XX, + 8. None of the 6 patients with 5q‐ chromosome and additional abnormalities in the same clone fulfilled all criteria. The ‘5q‐ syndrome’, a situation with the 5q‐ chromosome as a sole aberration, should be accepted as a diagnostic entity within the macrocytic anaemias. This syndrome can be suspected on the basis of the above haematological indicators and the diagnosis confirmed with bone marrow karyotype analysis.
Quantitation of hemoglobin in single erythrocytes with and without fetal hemoglobin
Authors: Meletis J. , Yataganas X. , Papavasiliou E. , Vaiopoulos G. , Fessas Ph.
Published: July 2010

The hemoglobin content was determined by microspectrophotometry in single erythrocytes with and without fetal hemoglobin (Hb F) from 16 normal subjects, 30 patients with anemia of different etiology and severity and 20 individuals with thalassemic disorders. Hb F‐containing cells were identified by an indirect immunofluorescent method. The relative single cell value: total extinction (TE) at 415 nm, cell size (A) and the ratio TE/A, were used to indicate single cell values of MCH, MCV and MCHC respectively. The TE (MCH) and/or TE/A (MCHC) did not differ significantly between Hb F‐containing (F‐cells) and non‐F cells in normal subjects and in cases with various forms of acquired anemia. On the contrary, the TE and/or TE/A of F‐cells was found significantly higher in F compared to non‐F cells in 11 of 20 (55%) of the cases with thalassemia. The results suggest that, in some cases of thalassemia, hemoglobin F is an important substitute for hemoglobin A and may improve the level of hemoglobinization.
Serum and plasma measurements of neutrophil granule proteins during cardiopulmonary bypass: A model to estimate human turnover of lactoferrin and myeloperoxidase
Authors: Venge P. , Nilsson L. , Nyström S‐O , Åberg T.
Published: July 2010

During extracorporeal circulation (ECC), granule proteins such as lactoferrin and myeloperoxidase escape to the plasma in large amounts. ECC was used to study the turnover of these proteins and compare their variations in plasma and serum. During ECC both proteins rose to very high levels and the variations were similar in both serum and plasma (r = 0.93 for lactoferrin and 0.80 for myeloperoxidase). The initial elimination after termination of operation (t1/2) was, for lactoferrin 0.75 and for myeloperoxidase 0.5 h. Both proteins followed a second order kinetics of elimination with a t1/2 for lactoferrin of about 9 and for myeloperoxidase of about 25 h. 48 and 72 h postoperatively serum levels, but not plasma levels, of myeloperoxidase rose again 10‐fold. We conclude that serum and plasma measurements of neutrophil granule proteins are complementary. The period after disconnection of the patient from the extracorporeal device may be used to estimate the turnover kinetics of neutrophil granule proteins.
Danazol in the treatment of myelodysplastic syndromes
Authors: Buzaid Antonio C. , Garewal Harinder S. , Lippman Scott M. , Durie Brian G. M. , Katakkar Suresh B. , Greenberg Bernard R.
Published: July 2010

20 patients with myelodysplastic syndromes (MDS) were treated with danazol, 800 mg daily in 4 divided doses. 18 patients were evaluable for response. 3 patients (17%), whose principal problem was anemia, responded to treatment, but only with an increase in platelet count. Responses were short‐lived and lacked clinical significance. No patients with anemia or leukopenia responded to treatment and none of the 7 patients with a platelet count less than 30 times 109/l responded. Danazol appears to have limited clinical utility in the treatment of MDS. However, occasional patients with thrombocytopenia may benefit.
Primary splenic hairy cell leukaemia: A case report and review of the literature
Authors: Ng Jean‐Pierre , Hogg R. B. , Cumming R. L. C. , McCallion J. , Catovsky D.
Published: July 2010

Hairy cell leukaemia affecting primarily the spleen is a very rare feature of this disease at presentation. Splenectomy in such cases would seem to provide a cure. We report a case of primary splenic hairy cell leukaemia in which clinical and haematological remission were achieved after splenectomy, and we review the literature.
The significance of HIV antigen and HIV antibodies specific against envelope and core proteins in serum of HIV‐infected hemophiliacs
Authors: Rollag Halvor , Evensen Stein A. , Frøland Stig S. , Glomstein Anders
Published: July 2010

Serial serum samples from the 21 HIV‐infected Norwegian hemophiliacs have been assayed for the presence of HIV antigen and antibodies to HIV specific for the core protein p24 and the envelope protein gp41. HIV antigen was detected in 4 patients, of whom 3 have developed AIDS to date. HIV antigen appeared in serum 10 to 24 months before the diagnosis in these patients. Antibodies to gp41 was a constant finding. Antibodies to p24 disappeared from the serum in 1 patient who developed AIDS and from 3 persons free of symptoms related to the HIV infection. The detection of HIV antigen in HIV antibody‐positive hemophiliacs appears to be of considerable prognostic significance.
Hodgkin's disease, clinical stages IA to IIIB: Combined modality therapy (3 MOPP followed by curative and prophylactic radiotherapy including the spleen). Six‐year results
Authors: Colonna P. , Andrieu J. M. , Ghouadni R. , Zouaoui‐Benhadji Z. , Afiane M. , Kubisz P. , Tourani J. M. , Belhadj‐Merzoug K. , Schlienger M.
Published: July 2010

From January 1980 to September 1985, 82 patients with IA to IIIB clinical stage (CS) Hodgkin's disease were treated by three MOPP chemotherapy (CT) cycles followed by extended field radiotherapy (RT) including the spleen (30–40 Gy). 2 patients died during the treatment (medullary aplasia, pulmonary edema). 6 were in failure after three MOPP cycles; they received other CT; 3 died and 3 are alive in remission (survival: 2.5 to 3.5 yr). 74 were in complete remission (CR) after completion of treatment. 4 patients relapsed (all alive after re‐treatment) and 4 died in first CR (tuberculosis, hepatitis, myeloma, unknown cause). At 6 yr, actuarial survival and relapse‐free survival are respectively 89.8% for the 82 patients and 93% for those in CR. These good results are due to: the administration of CT before RT, limited to three cycles; identification of failures after CT; inclusion of the spleen in RT ports in all cases; and a short lumbo‐aortic port in CS I and II.
Weekly low‐dose cyclophosphamide and alternate‐day prednisone: An effective low toxicity regimen for advanced myeloma
Authors: Brandes Lorne J. , Israels Lyonel G.
Published: July 2010

10 of 20 patients with advanced myeloma treated with a simple regimen consisting of weekly low‐dose cyclophosphamide (C; 150–300 mg/m2; maximum weekly dose = 500 mg) given intravenously or orally, and alternate‐day oral prednisone (P; 50–100 mg) responded clinically and with a fall in serum M protein > 50% or urine M protein > 90%. 3 of these responders were previous primary treatment failures, all having received cyclophosphamide in combination with other drugs given at 3‐ to 4‐wk intervals. 2 patients treated with this regimen as primary therapy also responded. Although the median survival for the 10 responders was reached at 24.5 months, 3 patients remain alive and well 50+ months from the start of CP therapy. An additional 5 patients had disease stabilization or major improvement in bone pain and/or pancytopenia for over 12 months despite failure to meet strict criteria for response. The data suggest that disease control may be achieved by the more frequent scheduling of known active drugs such as cyclophosphamide (although it alone or in combination with other drugs may be ineffective when given at standard 3‐ to 4‐wk intervals) in combination with prednisone on a more continuous basis. This is an effective yet simple therapeutic approach to myeloma with the distinct advantage of less toxicity than the multiple drug regimens in current use. It may have particular applicability to patients who are elderly or debilitated or in patients in whom cytopenia is present initially or develops on standard melphalan/prednisone regimens.
Ferritin synthesis by monocyte‐derived macrophages in thalassemic patients with intrinsic iron overload
Authors: Saab Ghaleb A. , Jurjus Abdo , Sarrou Elias A.
Published: July 2010

Macrophage ferritin content was determined following culture of peripheral blood monocytes for a period of 8 d in 40% autologous plasma to render them mature macrophages. Ferritin content was measured prior to and following culture using the radioimmunoassay. The normal range of values was established in a group of 22 healthy volunteer blood donors. A significant increase in the ratio of macrophage/ monocyte ferritin was observed in every donor studied (range 1.2 ‐ 1.8, p < 0.001). Also, a further significant increase was observed when these macrophages were additionally incubated for 6 h with heterologous antibody‐coated sheep red blood cells (range 1.2 ‐ 1.57, p < 0.001). Finally, the same studies were performed on a group of thalassemic patients with and without intrinsic iron overload. Again there were significant increases in monocyte ferritin content following culture as well as ingestion of heterologous sheep red cells, with magnitudes similar to those obtained with normal donor monocytes. Therefore we could not demonstrate the presence of a cellular ferritin synthesis defect in macrophages of thalassemic patients with intrinsic iron overload to explain the uncontrolled absorption of dietary iron from their gut.
Heterogeneity of TdT +, HLA‐DR + acute leukaemia: Immunological, immunocytochemical and clinical evidence of lymphoid and myeloid origin
Authors: Basso Giuseppe , Putti Maria Caterina , Catoretli Giorgio , Consolini Rita , Galdiolo Donata , Guglielmi Cesare , Messina Chiara , Milanesi Carla , Testi Anna Maria , Xillo Marta Zillo Monte , Zulian Francesco , Foá Robert
Published: July 2010

15 cases of acute leukaemia (AL) displaying a TdT +, HLA‐DR + phenotype were studied; surface immunoglobulins, T cell markers and the common acute lymphoblas‐tic leukaemia (c‐ALL) antigen were negative, as were peroxidase and non‐specific esterase cytochemical reactions. All cases were extensively investigated by conventional immunofluorescence (IF) and immunoperoxidase (IP), with a panel of monoclonal antibodies (MoAb), using both light and electron microscopy, and for ultrastructural myeloperoxidase (MPO). 8 cases, which were OKB2+, BA1 +, B4+, J5‐ and BA2‐by IF, expressed the J5 antigen in IP. These cases were therefore re‐classified as ALL with a weak expression of the C‐ALL antigen. The other 7 cases showed an OKB2‐, BA1‐, B4+, BA2+ phenotype at IF and were also positive for 1 or more anti‐myeloid MoAb. These features were confirmed by IP study. 4 patients also presented ultra‐structural positivity to MPO. These cases were considered as proliferations of early precursor cells capable of expressing both myeloid and lymphoid features. This study, while demonstrating the heterogeneity of TdT +, HLA‐DR + AL, suggests that the cell origin of many cases may be defined by extensive immunotyping at both IF and IP level. The prognostic and therapeutic implications of these findings are discussed, also in view of the poor prognosis often observed in the more undifferentiated cases of AL.
Migration of leukaemic lymphocytes (chronic lymphocytic leukaemia) through a 3‐D collagen gel: a possible prognostic factor
Authors: Shiu W. , Schor S. , Chang J. , Crowther D.
Published: July 2010

Migratory properties of malignant lymphocytes in 27 patients with chronic lymphocytic leukaemia (CLL) were investigated using 3‐D collagen gel. There was significant impairment of migration in malignant lymphocytes as compared with normal lymphocytes. Moreover there was an inverse correlation between Rai's staging and the migration index. Patients with progression of disease also showed a decrease in migration index. There was no correlation between kappa and lambda type in terms of migration index. The prognostic significance of the migratory properties of malignant lymphocytes is also discussed.
Survival and prognostic factors in chronic lymphocytic leukemia
Authors: Pines Amos , Ben‐Bassat Isaac , Modan Michaela , Blumstein Tzvia , Ramot Bracha
Published: July 2010

The survival of 137 consecutive chronic lymphocytic leukemia patients, diagnosed between 1960 and 1982 and followed up at the Hematology Clinic of the Chaim Sheba Center, was correlated with demographic, clinical and laboratory data. The median survival time of the whole group was 104 months. Older age, hepatomegaly, anemia, thrombocytopenia and increased percent of lymphocytes in the peripheral blood at diagnosis were all associated with shorter survival. On the other hand, splenomegaly or lymph node enlargement did not influence survival. When divided according to both Rai's and the International Workshop staging systems, the survival of our patients seemed to be better than that reported in most previously published series of similar patients. We assume that this is related to a conservative approach to the treatment of chronic lymphocytic leukemia patients in this center.
Incidence and clinical significance of protein‐bound vitamin B12 malabsorption
Authors: Jones B. P. , Broomhead A. F. , Kwan Y. L. , Grace C. S.
Published: July 2010

Patient records from January 1975 to December 1984 were analysed to assess the possible incidence of protein‐bound vitamin B12 malabsorption. This condition is characterised by a low serum vitamin B12 level and a normal Schilling test but impaired absorption of vitamin B12 bound to protein. We found that 48 (25%) patients with a low serum cobalamin level unexplained by other causes had a normal Schilling test. Megaloblastic haemopoiesis was found in 25 of these. From this group, all 10 patients who had a test of protein‐bound vitamin B12 absorption showed impaired absorption. Protein‐bound vitamin B12 malabsorption may represent an early phase of pernicious anaemia when hypochlorhydria precedes intrinsic factor deficiency and should be tested for when the serum vitamin B12 level is decreased and the Schilling test is normal.
Modulation of human erythropoiesis by hydrocortisone in vitro
Authors: King Derek J. , Koekebakker Marijke , Barr Ronald D.
Published: July 2010

The effect of hydrocortisone on the formation of erythroid colonies was studied in vitro in cultures of normal human bone marrow in an agar system. A range of concentrations of hydrocortisone (10‐10 to 10‐3 mol/1) showed significant effects on erythroid burst formation, in terms of the number of colonies, on d 10 and 14 of culture. At subphysiological concentrations (10‐10 to 10‐8 mol/1), no effect was seen, but at both physiological (10‐7 mol/1) and pharmacological (10‐6 and 10‐5 mol/1) concentrations stimulation of erythroid burst formation was noted. At 10‐4 mol/1 hydrocortisone inhibited erythroid colony formation and 10‐3 mol/1 was uniformly lethal. In the concentration range of 10‐7 to 10‐5 mol/1 hydrocortisone also appeared to increase erythroid colony size. Thus hydrocortisone (10‐7 to 10‐5 mol/1) stimulates erythroid colony growth and it is suggested that the hormone may play a role in the physiological regulation of human erythropoiesis.
Low serum cobalamin levels occur frequently in the acquired immune deficiency syndrome and related disorders
Authors: Burkes Ronald L. , Cohen Hartley , Krailo Mark , Sinow Robert M. , Carmel Ralph
Published: July 2010

Low serum cobalamin levels in 10 patients with AIDS or AIDS‐related complex led us to also prospectively survey 40 homosexual men in our AIDS clinic. 8 of the latter (20%) had low cobalamin values. We found no evidence of megaloblastic changes in the blood or bone marrow. Assessment disclosed malabsorption of cobalamin in only 1 of 6 cases tested for it. 6 of the patients were treated with cobalamin and had no hematologic response. It appears that low serum cobalamin levels in AIDS and related disorders do not usually represent overt cobalamin deficiency. While malabsorption is occasionally responsible for the low cobalamin level, in most cases the cause is unknown and may reflect a serum abnormality similar to that in multiple myeloma. AIDS and related disorders should be considered in the differential diagnosis of unexplained low cobalamin levels.