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E Juvonen

Publications and source records attributed to E Juvonen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Development of erythrocytosis in the course of essential thrombocythemia.

Erythrocytosis is not a feature of essential thrombocythemia (ET); this is the most important difference between ET and polycythemia vera (PV). Transformation of ET to PV has only rarely been described. We have reviewed the blood cell counts of 170 ET patients with a median follow-up of 63 months (range 11-313). Eleven of 170 patients (6.5%) developed erythrocytosis at a median of 29 months (range 12-138) after the diagnosis of ET. According to the present results, the development of erythrocytosis in patients with ET is not a rare phenomenon.

Adult↗
PubMed1999

Podocalyxin in rat platelets and megakaryocytes.

Podocalyxin is a membrane protein of rat podocytes and endothelial cells. It has not been described in other cell types, and no amino acid or DNA sequence data are available about it. Here we show that podocalyxin antigens are present in rat platelets and megakaryocytes. In resting platelets, the antigens are mainly intracellular but become surface exposed after thrombin stimulation, as shown by immunofluorescence and flow cytometry. By Western blotting, platelet podocalyxin has an apparent Mr of 140,000. Cytocentrifuge slides of rat bone marrow show that anti-podocalyxin antibodies recognize large polyploid cells also expressing CD62P, indicating that the cells are megakaryocytes. From a rat glomerular cDNA library we isolated a clone covering the carboxyl-terminal nucleotides of rat podocalyxin. Its putative transmembrane or intracellular domains are 100% or >93% identical, respectively, with the human and rabbit podocalyxin-like proteins. The truncated extracellular domain extends to include two of the four conserved cysteines shared by podocalyxin-like proteins. By Northern blotting, a 5.5-kb renal cortical transcript is seen. By in situ hybridization, cRNA probes recognize podocytes, endothelial cells, and megakaryocytes, and by reverse transcription polymerase chain reaction, platelets are shown to contain podocalyxin mRNA. Our results show that rat podocalyxin is a homologue of the previously cloned podocalyxin-like proteins and suggest that also in mammals podocalyxin has a role in hematopoiesis, as previously shown in the chicken.

Amino Acid Sequence↗
PubMed1999

The prognostic value of in vitro cultures of erythroid and megakaryocyte progenitors in myelodysplastic syndromes.

The prognostic value of colony formation by granulocyte-macrophage progenitors (CFU-GM) in myelodysplastic syndromes (MDS) has been investigated in several studies. We studied the in vitro growth patterns of hematopoietic progenitors of 83 patients with an MDS to find out whether erythroid (BFU-E) and megakaryocyte (CFU-Meg) cultures yield additional prognostic information to that obtained with CFU-GM cultures. Thirty-nine of 82 patients showed normal CFU-GM colony formation; the others had either excessive growth of colonies/clusters or reduced growth. Five of 74 patients had normal BFU-E and nine of 39 patients normal CFU-Meg growth; the others showed reduced or absent colony formation. The cultures of each cell lineage had a similar prognostic impact: the patients with a normal growth pattern had a lower risk of developing leukemia and a longer survival than those with an abnormal growth pattern (significant difference or trend). All patients with normal BFU-E or CFU-Meg colony growth also had normal CFU-GM colony formation, and all patients with normal BFU-E growth also had normal CFU-Meg growth. Among the patients with normal CFU-GM cultures, those with normal erythroid or megakaryocyte colony formation had a trend towards a better outcome compared to those with an abnormal growth pattern in the same cell lineage. In conclusion, erythroid and megakaryocyte cultures did not significantly contribute to the prognostic information obtained with CFU-GM cultures in MDS.

Cells, Cultured↗
PubMed1999

Variant Bernard-Soulier syndrome due to homozygous Asn45Ser mutation in the platelet glycoprotein (GP) IX in seven patients of five unrelated Finnish families.

Bernard-Soulier syndrome (BSS), a rare bleeding disorder with macrothrombocytopenia, is caused by a defect of the platelet glycoprotein (GP) Ib/IX/V complex. Here we report a variant form of BSS in eleven patients of five unrelated families who originate from a particular area of Finland. The differential diagnosis from idiopathic thrombocytopenic purpura was difficult. Bleeding symptoms were epistaxis and haematomas debuting in childhood, but no spontaneous, severe bleeding episodes were reported. The platelet count varied from 43 to 81x10(9)/l. Screening the entire GP Ibalpha, GP Ibbeta, GP IX and GP V genes revealed a recurrent homozygous Asn45Ser mutation in GP IX in all probands. Flow cytometry showed markedly reduced expression of GP Ib (<10%), and only moderately reduced expression of GP IX (24-36%) and GP V (38-49%). The expression of subunits seemed to vary independently from the normal polymorphisms. Heterozygotes did not differ significantly from controls by their GP Ib/IX/V expression. Since the Asn45Ser mutation has also been reported in three other kindreds of northern and central European origin, this study reveals that instead of being a mutation hot spot, it may be ancient and scattered in Europe. Moderate, chronic thrombocytopenia should be carefully studied to diagnose variant BSS correctly from treatment resistant idiopathic thrombocytopenia.

Amino Acid Substitution↗
PubMed1998

Essential thrombocythemia at diagnosis: causes of diagnostic evaluation and presence of positive diagnostic findings.

The reasons for diagnostic evaluation and the clinical and laboratory data at diagnosis of 170 patients with essential thrombocythemia (ET) were studied retrospectively. The age distribution was 19-88 years (median 52 years), and 52 patients were under the age of 45 years. In 111 patients (65%) thrombocytosis was a chance finding, but the past history of 37 of these patients revealed symptoms known to be related to ET. The diagnosis was based on a chance finding in a significantly higher proportion of female (74%) than male (53%) patients. The diagnosis of ET is based mostly on negative findings, i.e., on the exclusion of other causes of thrombocytosis, and positive diagnostic tests would be useful. We evaluated the presence of positive diagnostic findings of myeloproliferative disorders in ET. Splenomegaly was seen in 26% and an abnormal karyotype in 5% of the patients. Abnormal megakaryocyte morphology was seen in 80%, abnormal in vitro growth of hematopoietic progenitors in 74%, and abnormal platelet function in 83% of the patients. Both in vitro cultures of hematopoietic progenitors and platelet functions were studied in 36 patients, and in only two of these were both tests normal. We conclude that in most patients with ET the diagnosis can be strongly supported by positive findings, especially by in vitro cultures of hematopoietic progenitors and studies of platelet function.

Adult↗
PubMed1997

Granulocytopenia in Cohen syndrome.

Cohen syndrome is an autosomal recessive disorder characterized by mental retardation, microcephalia and typical craniofacial features, myopia and chorioretinal dystrophy. As some patients were reported to have leucopenia, we collected the haematological data of 26 Finnish Cohen patients. They all had experienced periods of isolated granulocytopenia from an early age. Granulocytopenia was mild to moderate, non-cyclic and never fatal. Most patients suffered from prolonged or repeated gingival or skin infections. We restudied 16 patients. Bone marrow examination revealed in all patients a normo- or hypercellular marrow, with a left-shifted granulopoiesis in 8/16 patients. The response to adrenaline stimulation was subnormal in 12/14 and to hydrocortisone in 8/16 patients, but administration of rhG-CSF caused granulocytosis in the three patients studied. No bone marrow malignancies were seen.

Adolescent↗
PubMed1997

Proposal for revised diagnostic criteria of essential thrombocythemia and polycythemia vera by the Thrombocythemia Vera Study Group.

The present study revises the criteria of the Polycythemia Vera Group (PVSG) for the diagnoses of essential thrombocythemia (ET) and polycythemia vera (PV) in view of accumulating data on in vitro cultures of hematopoietic progenitors and by adding histopathology from bone marrow biopsies. The majority of ET patients show spontaneous megakaryocyte or erythroid growth or both, but in about 35% the growth pattern is normal. So far none of the patients with reactive thrombocytosis have shown either spontaneous megakaryocyte or erythroid colony growth. Virtually all PV patients show spontaneous or endogenous erythroid colony (EEC) formation, whereas patients with secondary erythrocytosis and healthy controls do not show any erythroid colony growth in the absence of erythropoietin (EPO). Some rare patients with a disorder other than a myeloproliferative disease (MPD) may show spontaneous growth of erythroid colonies caused by a mutation in the EPO receptor. Megakaryocytes in bone marrow smears and biopsy material from ET and PV patients are typically increased in number and size. Enlarged megakaryocytes with mature cytoplasm and multilobulated nuclei and the tendency of these megakaryocytes to cluster in a normal or slightly increased cellular bone marrow represent the diagnostic hallmark of ET. Increase and clustering of enlarged, mature, and pleiomorphic megakaryocytes in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses is the diagnostic feature of untreated PV. In reactive thrombocytosis and secondary erythrocytosis the size and morphology of megakaryocytes remain normal and there is no tendency of the megakaryocytes to cluster. Both spontaneous EEC and histopathology of bone marrow biopsies appear to offer specific clues to the diagnosis of overt and latent ET or PV and have the potential to differentiate ET from reactive thrombocytosis and PV from secondary erythrocytosis. Moreover, bone marrow histopathology has the diagnostic power to distinguish and to stage the various MPDs without regard to clinical and laboratory data.

Biopsy↗
PubMed1996

Granulocyte-colony-stimulating factor after allogeneic and autologous bone marrow transplantation in children.

We evaluated the use of granulocyte CSF (G-CSF) after both allogeneic BMT (allo-BMT) and autologous BMT (ABMT) in children. After allo-BMT, G-CSF was used in 15 children who were compared with 20 historical controls. The ABMT patients were two sequential groups: the G-CSF group of 13 children and 11 historical controls. The patients were conditioned with different high-dose chemotherapy regimens with or without total body irradiation. G-CSF was administered at 5 micrograms/kg/day s.c. and was continued until an absolute neutrophil count (ANC) of 1,000 x 10(6)/l was reached. Following allo-BMT, G-CSF accelerated myeloid engraftment with a difference of 5 days at the ANC level of 500 x 10(6)/l (P<0.02) and 9 days at 1,000 x 10(6)/l (P<0.001). In the ABMT patients, G-CSF also accelerated myeloid engraftment. The difference between the G-CSF group and the control group was 6 days at ANC 200 (P<0.05), 11 days at ANC 500 (P<0.02) and 17 days at ANC 1,000 (P<0.005). In the ABMT patients, benefit by G-CSF was also observed in a smaller number of days with fever and days on antibiotics. We conclude that G-CSG significantly accelerated myeloid engraftment, after both allogeneic and autologous BMT in children, and also decreased the duration of febrile illness in the ABMT patients.

Adolescent↗
PubMed1996

Long-term bone marrow cultures in polycythaemia vera and essential thrombocythaemia.

Bone marrow samples of 8 patients with essential thrombocythaemia and three patients with polycythaemia vera were cultured in long-term bone marrow cultures. The production of non-adherent cells and colony-forming unit-granulocyte-macrophage harvested weekly did not differ from that of 29 healthy bone marrow transplant donors. There was a trend towards less complete stromal confluence in patients with a myeloproliferative disease.

Adult↗
PubMed1996

Invasive cutaneous mucormycosis caused by Absidia corymbifera after allogeneic bone marrow transplantation.

Mucormycotic infections caused by fungi of the families Rhizopus, Mucor or Absidia are rare and usually associated with diabetes or immunosuppression. We describe a patient with invasive necrotizing cutaneous mucormycosis caused by Absidia corymbifera shortly after allogeneic BMT. The infection was successfully treated with surgical debridement and liposomal amphotericin B for 6 weeks. Recognition of these rare infections requires a high index of suspicion. These patients should be evaluated with tissue biopsy and cultures and treated without delay.

Adult↗
PubMed1995

Defective in-vitro colony formation of haematopoietic progenitors in patients with cartilage-hair hypoplasia and history of anaemia.

UNLABELLED: Cartilage-hair hypoplasia (CHH) is a metaphyseal chondrodysplasia with short-limbed short stature. The CHH gene has been recently mapped to chromosome 9, and a generalized defect in cellular proliferation has been suggested. Immunological and haematological abnormalities are common findings in CHH. In the present study erythroid, megakaryocyte, and granulocyte-macrophage colony formation in vitro by progenitors from bone marrow and blood was investigated in eight patients with CHH. All patients showed decreased erythroid and megakaryocyte colony formation. Only one patient had a normal granulocyte-macrophage growth, while the others showed decreased numbers of colonies. The defect in colony formation did not correlate with the haemoglobin concentration, platelet count or neutrophil count. The impaired growth was not caused by a decreased number of progenitors as shown by erythroid cultures. The erythroid progenitors were incapable of colony formation in culture conditions sufficient for colony formation by normal progenitors. In a more effectively stimulated culture assay the number of erythroid progenitors was normal or increased. CONCLUSION: The present study shows defective in vitro colony formation in all myeloid lineages in patients with CHH, which is in accordance with the suggestion of a common cell proliferation defect in CHH.

Adolescent↗
PubMed1995

Idiopathic macrocytic anaemia in the aged: molecular and cytogenetic findings.

Macrocytosis in the elderly is often caused by abnormalities of haematological stem cell differentiation. In this study, a group of elderly patients was analysed for four molecular and cell biological parameters. The aim of the study was to screen elderly patients with idiopathic macrocytic anaemia or MDS for a set of alterations which are related to haematological dysplasia. The analyses used were: DNA-methylation at the calcitonin A gene 5'-area, NRAS point mutations at codons 12 and 13, in vitro colony formation of peripheral blood progenitor cells and cytogenetics of bone marrow cells. The results show that a significant portion of elderly patients with idiopathic macrocytosis have one or more of the abnormalities analysed. Hypermethylation of the calcitonin A gene 5'-area at the chromosome 11 band p15 is relatively common (7/15). Chromosomal aberrations (3/12) and NRAS oncogene point mutations (0/15) were rare findings. In vitro culture of erythroid progenitor cells was relatively frequently abnormal (7/15). Eight of our nine macrocytic patients who did not fulfill the FAB criteria for MDS had at least one of the alterations studied; this suggests that these patients might represent early phases of a stem cell disorder.

Aged↗
PubMed1995

Reemphasis on leukocyte transfusions: induction of myeloid marrow recovery in critically ill neutropenic children with cancer.

Neutropenia is the major factor predisposing to sepsis in cancer patients, and its duration is important for survival. We administered leukocyte transfusions (LT) to 10 children suffering from documented life-threatening infections during profound, prolonged neutropenia. Nine had acute leukemia, and one had aplastic anemia; three were bone marrow transplant recipients. These 10 were the only patients in our unit who received LT during the past 7 years. The median leukocyte dose was 0.6 x 10(9)/kg in total. Instead of leukapheresis products, we used pooled buffy coats from random donors, with a high relative content of lymphocytes and especially T lymphocytes. The leukocyte concentrates were irradiated with 15 Gy. In all 10 patients, we observed prompt and sustained myeloid marrow recovery following LT. Such an effect of LT has never been described before. We hypothesize that in the internal milieu of these aplastic patients the transfused leukocytes were stimulated to secrete cytokines, the result being a cascade-like phenomenon and stimulation and proliferation of the patient's own bone marrow cells. The bone marrow-stimulating effect of LT merits further study.

Acute Disease↗
PubMed1994

Immuno- and cytochemical characterization of congenital leukemia: a case report.

Congenital leukemia (CL) is a rare disorder, which usually presents as a myelocytic leukemia based on morphological features. Very few reports include data on cyto- or immunochemical parameters. A case of CL with detailed description of immunochemical, cytochemical features, and colony formation properties of the progenitor cells is reported. This leukemia was classified as an M4 in FAB classification based on the morphological features and special stains. Two different cell populations were identified by flow cytometry. One consisted of small cells expressing early T- and early B-cell associating antigens as well as early myeloid-associated antigens, but not CD10 (CALLA antigen), which is normally present in cord blood lymphocytes. The other was a population of large cells expressing myeloid-associated antigens and a pan-T-antigen. The growth pattern of hematopoietic progenitors in the patient was compatible with both acute myeloid and acute lymphatic leukemia as well as erythroleukemia.

Bone Marrow↗
PubMed1994

Calcitonin gene methylation in chronic myeloproliferative disorders.

Alterations in DNA methylation appear to be an integral part of the malignant transformation. For example, the p15 region of chromosome 11 with multiple genes related to cell growth regulation exhibits different methylation patterns in the 5' area of the calcitonin A gene in healthy bone marrow cells, and in leukemic cell populations. In this work the methylation status of the 5' area of the calcitonin gene in myeloproliferative disorders (MPD) other than chronic myeloid leukemia (CML) is studied. A total number of 37 patients with polycythemia vera, essential thrombocythemia, or myelofibrosis were studied. A control group of 18 healthy persons and patients with reactive hematologic changes was included. The DNA isolated from peripheral blood or bone marrow cells was digested with the methylation-sensitive HpaII restriction enzyme. A Southern blot was hybridized with a 1.7 kb probe specific to the 5' area of the calcitonin gene. The result was visualized autoradiographically and analyzed with a densitometer. The results have been expressed as ratios between the abnormal and normal autoradiography band intensities, referred to as the calc-value or CALC. An increase in the calc-value signifies increasing methylation. In the control group the calc-value had a mean of 0.274. The myelofibrosis patients exhibited very strong hypermethylation in the calcitonin gene 5' area, with a mean calc-value of 11.1 (median 2.6). The polycythemia vera patients showed considerable variation in their methylation status, with a mean value of 1.52. The essential thrombocythemia patients exhibited weak hypermethylation, with a mean calc-value of 0.58. A correlation between karyotypic abnormalities and hypermethylation was observed. Complicated forms of MPD exhibited higher levels of methylation than the uncomplicated disease forms.

Adult↗
PubMed1993

Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis.

Erythropoietin regulates the proliferation and differentiation of erythroid precursor cells. Its effect is mediated by the erythropoietin receptor (EPOR), a member of a large family of cytokine receptors. The EPOR gene has recently been cloned, sequenced, and characterized. As shown experimentally, its intracellular C-terminal part contains a domain exerting negative control on erythropoiesis. Here we describe a G to A transition in nucleotide 6002 of the EPOR gene that converts a TGG codon for tryptophan into a TAG stop codon, predicting the truncation of the 70 C-terminal amino acids of the EPOR molecule. The mutation occurs in heterozygous form in the germ-line DNA of members of a large kindred in which primary erythrocytosis is segregating as a mild autosomal dominant trait. The mutation cosegregates with the disease phenotype in all 29 affected family members studied; it occurs in no unaffected family members or unrelated controls. This appears to be an example of a human condition caused by an EPOR mutation. Striking similarities exist between the human phenotype described here and phenotypes of cell lines expressing similarly truncated EPOR molecules produced experimentally. By analogy with these in vitro studies, one can hypothesize that the truncated EPOR molecules are activated by suppression of phosphorylation leading to loss of the down-modulation exerted by intact EPOR molecules. Experimental modifications of the EPOR gene may eventually have therapeutic applications.

Base Sequence↗