Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 51-year-old man had suffered from massive pleural effusion due to invasion of malignant cells. The analysis of bone marrow aspiration showed the proliferation of myeloperoxidase-positive blasts. The surface marker analysis of the blasts revealed the positivities for CD7 and CD19 as well as CD13, CD33 and CD34, while the karyotypes of 20 cells were normal. Therefore, CD7 positive AML was diagnosed. The patient was treated with araC and daunorubicin as a remission induction therapy. Peripheral blood stem cells were harvested by leukapheresis after first and second consolidation therapies. Then, 3 x 10(4) cells/kg of CFU-GM were infused. Complete remission has been maintained for 8 months after autologous blood stem cell transplantation. Pleural involvement as an initial manifestation is rare in AML. Extramedullary growth of AML cells may be related to their immaturity, indicated by the expression of the cell surface antigens.
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PMID:[CD7 positive acute myelogenous leukemia exhibiting pleural involvement as an initial manifestation]. 752 3

Reports of treatment of patients with minimally differentiated acute myeloid leukemia (AML-M0) are limited, heterogeneous, and controversial. We verified the prognosis of this subtype by analyzing the results of 189 consecutive patients with de novo AML. Fifteen cases fitting the criteria of AML-M0 were identified. No clinical features distinguished them from other patients with AML. The median age was 61 years (range 27 to 70), with a leukocyte count ranging from 0.6 to 185 x 10(9)/L. In all cases the leukemic cells expressed CD34 and reacted with at least one of the antibodies to early myeloid antigens, ie, CD13, CD33, or myeloperoxidase. Immunophenotypic analysis also showed positivity for CD7 in seven samples and the multidrug-resistance P-glycoprotein (P-170) in six. Cytogenetic analysis was abnormal in 12 of the 13 patients in whom an adequate number of mitoses could be evaluated. No single abnormality prevailed, the most common findings being trisomy 8 (three cases) and aberrations of chromosome 7 (two cases). Antileukemic treatment differed according to age, but for remission induction, all patients received a combination of cytosine arabinoside and an anthracycline or mitoxantrone. The prognosis of patients with AML-M0 was remarkably poor as compared with the other French-American-British subtypes. Whereas the overall rate of complete remission (CR) was 58% with a median survival of 63 weeks, only 6 of the 15 patients with AML-M0 achieved a CR, and the median survival of this group was 16 weeks (range 3 to 39). The major determinant of treatment failure was unresponsiveness to chemotherapy, as only one patient died of infection during the hypoplastic phase. The CR duration of responders was short, ranging from 3 to 22 weeks, and no second remissions were observed. We conclude that conventional combination chemotherapy yields disappointing results in AML-M0. The reason for this may be the convergence of various unfavorable prognostic factors, such as (1) the high incidence of cytogenetic abnormalities; (2) the lack of differentiation features and the expression of immaturity markers such as CD34 and CD7; and (3) the frequent expression of P-170. Nonconventional therapeutic approaches should be developed to alter the prognosis of this form of leukemia.
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PMID:Analysis of treatment failure in patients with minimally differentiated acute myeloid leukemia (AML-M0). 812 53

Recent evidence has suggested that the immaturity of the neonatal intestine may play a key role in the development of ischemic injury. However, relatively little data exist on the susceptibility of the neonatal intestine to ischemic injury at various ages especially in the fed versus fasted states. In this study, the levels of xanthine oxidase ([XO] an enzyme which is a known, major source of free radicals in postischemic tissue) and myeloperoxidase ([MPO] an index of tissue neutrophil infiltration) were measured in 1-, 5-, 10-, 15-, and 20-day-old Sprague-Dawley rats. Rats were divided into fed (n = 8/day) and fasted (n = 8/day) groups 4 hours prior to sacrifice. The entire small intestine was removed and divided into five segments: the duodenum, proximal jejunum, distal jejunum, proximal ileum, and distal ileum. The specimens were homogenized and assayed for XO and MPO levels. A significant increase in XO was observed in the fasted animals compared to the fed animals on all days. Peak levels in XO were observed in both groups from day 5 to 10. MPO levels were significantly higher in the fasted versus fed animals on day 1. MPO levels decreased as the animals aged. These data demonstrate dramatic differences in the levels of inflammatory enzymes of the newborn rat in the fed versus fasted states. Also, marked variations with age are seen in both XO and MPO. Whether the XO and MPO levels present at the time of ischemic insult affect severity of injury remains to be seen.
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PMID:Inflammatory enzyme composition of the neonatal rat intestine: implications for susceptibility to ischemia. 839 43

The current hypothesis for the pathogenesis of myelofibrosis involves the intramedullary release of growth factors from defective or abnormal megakaryocytes. We describe a case of an acute micromegakaryocytic leukaemia, in a patient with chronic myelofibrosis, that provides additional evidence for this concept. The micromegakaryocytes, which reached 223 x 10(9)/l, were characterized morphologically by both light and electron microscopy, immunocytochemically and by platelet peroxidase activity. The cells were shown to have a mature cytoplasm, containing alpha granules and the associated proteins; vWF:Ag, fibrinogen, fibronectin and protein S. DNA analysis, by both a Seescan Solitaire Plus image analysis system and flow cytometry, revealed nuclear immaturity, with 92% of cells being diploid. Serum markers of connective tissue synthesis, namely carboxy terminal peptide of procollagen I (PICP), procollagen terminal peptide III (PIIIP) and laminin all increased significantly following transformation and were associated with an increase in platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta). These observations support the current hypothesis for bone marrow fibrosis formation and provide, for the first time, a link between in vivo growth factor release, bone marrow stromal turnover and megakaryocyte mass. In addition, the release of biologically active TGF-beta may explain both the increased fibronectin and angiogenesis characteristic of myelofibrotic bone marrow.
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PMID:Characterization of an acute micromegakaryocytic leukaemia: evidence for the pathogenesis of myelofibrosis. 843 38

Neuron addition is one means whereby the nervous system can compensate for increased body size. Neurons can be added either by mitosis of stem cells or by late differentiation of committed precursors. Previously, the doubling of hind limb dorsal root ganglion (DRG) neurons in postmetamorphic bullfrogs (Rana catesbeiana) was found to occur in the absence of neuron proliferation (St. Wecker and Farel [1994] J. Comp. Neurol. 342:430-438). In the present study, we identify a population of cells in the DRGs of juvenile frogs that lack the appearance typical of sensory neurons yet are immunoreactive to a neuron-specific probe for neurofilament protein. These less differentiated (type-L neurons) could not be labeled retrogradely with horseradish peroxidase from the periphery or dorsal root. Despite their apparent immaturity, type-L neurons appear to have extended axons both centrally and toward the periphery, because axon number in dorsal roots and peripheral nerves was similar in juvenile and adult frogs. These findings are consistent with the existence in juvenile frogs of a population of incompletely differentiated DRG neurons that lack the physiological properties and appearance typical of mature neurons.
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PMID:Neuron addition during growth of the postmetamorphic bullfrog: sensory neuron and axon number. 942 Nov 39

Precise point-to-point connectivity is the basis of ordered maps of the visual field. The immaturity of the newborn hamster's visual system has allowed us to examine emerging topography in the geniculo-cortical projection well before thalamic axons have reached their cortical target, layer IV. Using anterograde transneuronal labeling with wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), we visualized the ingrowth of the whole population of geniculate fibers in the neonatal hamster. Two days after birth (P2), the bulk of the fibers is in the deep cortical layers and the subplate. At the same age, injections of paired retrograde tracers (red and green fluorescent latex microspheres) into area 17 reveal an unordered projection from the dorsal lateral geniculate nucleus (dLGN) to cortex. Individual labeled cells are found throughout the dLGN, and quantitative analysis reveals no segregation of the red and the green populations. At P6, when the pattern of geniculate back label appears ordered and essentially adult-like, geniculate fibers have reached layer IV. The role of selective cell death in this process was investigated by making a tracer injection at P2 and allowing the animals to survive to P6 or P12, when the map is mature. The results show early labeled neurons that made inappropriate connections when the projection was scattered surviving through the period of geniculate cell death. We conclude that the geniculo-cortical map develops from an initially unordered projection to the subplate and the lower cortical layers. Selective cell death appears not to contribute significantly to this process.
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PMID:The development of topography in the hamster geniculo-cortical projection. 967 65

The Bayer-Technicon hematological devices differentiate leukocytes by their peroxidase activity and their volume, displaying them as separate clusters. Peroxidase deficiencies are manifested by the irregular location of these clusters. This makes it possible to identify persons totally or partially lacking myeloperoxidase. The deficiency is quantified by the myeloperoxidase index, which is expressed for every routine analysis and for which normal values were determined. Values of the myeloperoxidase index confirm varying degrees of deficiency and prevalence. Family studies using these degrees show that the hereditary pattern must be more complicated than the classical autosomal-recessive mode. A bigenic mode is suggested. While about half of the totally deficient individuals detected were free of typical symptoms, in the other half we found infectious complications that were sometimes life-threatening. The hematological devices allow the identification of persons suffering from eosinoperoxidase deficiency and from MPO deficiency of the monocytes. The latter symptom seems to indicate immaturity of these cells and may lead to unexpected diagnosis of malignancy.
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PMID:Prevalence of myeloperoxidase deficiency: population studies using Bayer-Technicon automated hematology. 976 44

Hematopoietic progenitor cells from different sources have been widely characterized, but their ultrastructural morphology has never been described in detail. In this study, imunomagnetically separated CD34+ cells from normal bone marrow (BM), mobilized peripheral blood (PBSC) and human umbilical cord blood (CB) were studied by transmission electron microscopy (TEM) using a cytochemical method which reveals endogenous myelo-peroxidase (MPO) activity. This technique is particularly suited for detecting early signs of the myeloid commitment. The CD34+ cells from PBSC were morphologically very homogeneous and 94.7+/-4.5% of these cells were MPO-: these ultrastructural features are generally considered typical of immature cells. The CD34+ BM cells were instead more heterogeneous, with 24.6+/-7.4% showing intense MPO activity. The ultrastructural characteristics of CB cells fell between those observed in PBSC and BM, but there was a high percentage of morphologically immature cells with no evidence of MPO activity (about 83%). The number of apoptotic cells within samples from different sources was also examined both by TEM and flow cytometry. The percentage of apoptotic cells was 0.7% in PBSC, 2.3% in BM, 2.9% in CB from vaginal delivery and 11.6% in CB from cesarean section. These observations confirm the relative phenotypic immaturity of CB in comparison with BM cells; they also suggest that CB collected after cesarean section may be associated with reduced stem cells viability.
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PMID:Ultrastructural features of CD34+ hematopoietic progenitor cells from bone marrow, peripheral blood and umbilical cord blood. 1169

Knowledge of the blast phenotype in myelodysplastic syndrome (MDS) would be valuable, as in other malignancies, but remains sparse. This is mainly because MDS blasts are a minor population in clinical samples, making analysis difficult. Thus, for this blast phenotype study, we prepared blast-rich specimens (using a new density centrifugation reagent for harvesting blasts) from blood and marrow samples of 95 patients with various MDS subtypes and 21 patients with acute leukemia transformed from MDS (AL-MDS). Flow cytometry revealed that a high proportion of the enriched blast cells (EBCs) from almost all patients showed an immunophenotype of committed myeloid precursors (CD34(+)CD38(+)HLA-DR(+)CD13(+)CD33(+)), regardless of the disease subtype. The cytochemical reaction for myeloperoxidase was negative in 58% of the cases. Thus, the EBC phenotype is more immature in MDS than in de novo acute myeloid leukemia. MDS EBCs often coexpressed stem cell antigens and late-stage myeloid antigens asynchronously, but rarely expressed T- and B-lymphoid cell-specific antigens. Markers for myeloid cell maturation (CD10 and CD15) were more prevalent on EBCs from low-risk MDS (refractory anemia [RA] and RA with ringed sideroblasts), whereas markers for myeloid cell immaturity (CD7 and CD117) were more prevalent on EBCs from high-risk MDS (chronic myelomonocytic leukemia, RA with excess blasts [RAEB], and RAEB in transformation) and AL-MDS. A shift to a more immature phenotype of EBCs, accompanying disease progression, was also documented by sequential phenotyping of the same patients. Further, CD7 positivity of EBCs was an independent variable for a poor prognosis in MDS. These data represent new, valuable information regarding MDS.
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PMID:Clinical significance of phenotypic features of blasts in patients with myelodysplastic syndrome. 1239 41

Spleen is a common site of extramedullary hematopoiesis. Extramedullary hematopoiesis seen in non-neoplastic conditions can occasionally be extensive and raise concerns for a myeloid neoplasm. We compared the morphologic and immunohistochemical features of splenic hematopoietic proliferations seen in neoplastic myeloid disorders (eg chronic myeloproliferative disorders, myelodysplastic/myeloproliferative disorders and acute myeloid leukemias) to extramedullary hematopoiesis seen in a variety of reactive conditions. In all, 80 spleen specimens were reviewed. The presence of each marrow-derived lineage, dysplasia and immunohistochemical results were evaluated (CD34, CD117, myeloperoxidase, CD68, p53, TdT, CD42b and hemoglobin). Neoplastic hematopoietic proliferations in chronic myeloproliferative disorders are characterized by trilineage hematopoiesis with significant dysplasia in all cell lineages. Acute myeloid leukemia showed an increase in immature forms, which were highlighted by immunohistochemistry. Reactive extramedullary hematopoiesis showed variability in histologic features. Post-bone marrow transplant and thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome spleens showed extramedullary hematopoiesis with some morphologic features of immaturity, which could simulate chronic myeloproliferative disorder. However, they lacked characteristic immunohistochemical features of neoplastic myeloid disorders such as positivity for CD34 or CD117.
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PMID:Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders. 1611 26


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