PubMed Health⌕ Search

Biomedical subjects

M Zandecki

Publications and source records attributed to M Zandecki.

At least 55 records · Page 3Linked to original sources
PubMed1994

Inactivation of the retinoblastoma gene appears to be very uncommon in myelodysplastic syndromes.

Rearrangements of the retinoblastoma (RB) gene have been reported in a few cases of myelodysplastic syndromes (MDS). In addition, low or absent expression of the RB protein is found in 20-30% of cases of acute myeloid leukaemias (AML), particularly in AML with a monocytic component (M4 or M5). We performed Southern blot analysis of the RB gene in 90 cases of MDS, including 37 cases of chronic myelomonocytic leukaemia (CMML). None of them had progressed to AML at the time of study. In 37/90 patients (including 20 CMML) Northern blot analysis, study of RB protein by immunocytochemistry on bone marrow slides, and detection of point mutations in exons 20-24 of the RB gene was also made, using single strand conformation polymorphism analysis (SSCP). No abnormal Southern profile was found in any of the 90 patients. Northern blot and immunocytochemical study of RB protein were normal in the 37 cases studied. SSCP analysis detected a point mutation in 2/37 patients tested. Direct sequencing confirmed the mutation in each case, which involved intron 21 and intron 23, respectively, and was located outside splicing sites of the neighbouring exons. These findings suggest that abnormalities of the RB gene and its expression must be very rare in MDS, and play a minor role, if any, in the pathophysiology of those disorders, at least before progression to AML.

Base Sequence↗
PubMed1994

Over-expression of the MDM2 gene is found in some cases of haematological malignancies.

We looked for MDM2 gene amplification and over-expression by Southern and Northern blot analysis in 135 and 66 cases of haematological malignancies, including ALL, AML, CML in chronic phase, CLL, MDS, PLL, non-Hodgkin's lymphoma (NHL) and myeloma. No amplification of the gene was found. An over-expression of MDM2 RNA was seen in 9/66 (14%) patients tested, including 3/9 ALL, 3/24 AML, 2/4 myelomas, 1/1 PLL, but 0/2 CML, 0/2 NHL and 0/21 MDS. None of the patients over-expressing MDM2 had modifications of P53 gene transcript or p53 mutations. Most of the patients over-expressing MDM2 gene had poor prognostic features (including 'unfavourable' cytogenetic abnormalities), poor response to chemotherapy and short survival. Our findings suggest that over-expression of MDM2 is seen in a relatively small number of haematological malignancies, and is associated with poor prognosis.

Aged↗
PubMed1994

Significance of circulating plasma cells in multiple myeloma.

The number of circulating plasma cells (CPC) was determined on mononuclear cell preparations after Giemsa (morphology) and light chain staining (immunocytochemistry). Both methods gave reproducible and identical results when CPC were 1% or more. Using this limit, no CPC were observed in MGUS (0/11) and primary amyloidosis (0/2), whereas 45/98 (45.9%) multiple myeloma (MM) pts had > or = 1% CPC. 3/14 pts (21.4%) in stage I, 5/13 pts (38.5%) in stage II, 20/28 pts (71.4%) in stage III, 4/25 pts (16%) at plateau phase, and 13/18 pts (72.2%) at relapse had > or = 1% CPC (p < 0.001). Mean beta-2 microglobulin was 3.77 mg/l and 6.08 mg/l for pts without or with > or = 1% CPC, respectively p = 0.0001). Presence of CPC was also correlated with an higher percentage of bone marrow PC, but not with the number of Ki-67 positive BM-PC, and not with CRP or LDH levels. K/L and Gamma/Alpha CPC isotype ratio showed these cells as monotypic in nearly all pts. The prognostic value could not really be assessed in this study, as only the initial response to therapy was investigated, and the latter failed to give any difference between pts with and without CPC. So, presence of CPC is not an infrequent finding, but is highly related to tumor mass and active disease; in most if not all patients they are monotypic and certainly belong to the malignant clone. Their prognostic value is unclear but under current investigation; CPC are correlated with B-2M level.

Cell Count↗
PubMed1994

[Evaluation of Abbott CD 3500 in severe leukopenia].

Leucopenia patient follow-up remains, in terms of laboratory turnaround, a heavy workload due to the leucoconcentrations necessary for evaluating leucocytic formulas. We tested the CD 3500 with the objective of defining its' analytical performances and routine practice. 101 leucopenia samples (< 2.10(9)/l) procured from the onco-hematology department (adults and children) were studied during a 1 month period. The leucocytic formula obtained after leuconcentrations was our reference. The alarm sensitivity, as a whole, was of 97% for a 15.5% specificity. The correlation coefficients (Cell-Dyn/microscope) for polynuclears, lymphocytes and monocytes were respectively 0.889, 0.925 and 0.926. The correlation coefficients observed in both following subgroups: < or = 0.5.10(9)/l and > 0.5.10(9)/l were superposable. In 95% of the cases, the numeric value difference between the two methods attained a maximum of 21% for all neutrophils and lymphocytes and 13% for the monocytes. There was an excellent concordance between both methods for eosinophilia and basophils with confidence intervals of +/-8.8% and +/-2.2%. In practice, we feel that the use of a CD 3500 in post chemotherapy leucopenia, is perfectly adaptable and appreciated for leucocytic formulas, as well as a good exit for aplasia.

Autoanalysis↗
PubMed1993

Improved cytogenetic analysis of bone marrow plasma cells after cytokine stimulation in multiple myeloma: a report on 46 patients.

Cytogenetic analysis was successfully performed in 46 consecutive myeloma patients (40 newly diagnosed and six relapsed patients). Karyotype was performed on bone marrow cells after long-term cultures (6 d) stimulated by GM-CSF, GM-CSF+IL6 or GM-CSF+IL6+IL3. Nineteen patients (41%) had cytogenetic abnormalities including 17/40 patients at diagnosis (42.5%) and 2/6 patients at relapse. Hyperdiploidy was found in 12 patients and hypodiploidy in four patients. Of the 17 newly diagnosed patients with cytogenetic abnormalities, five died from myeloma after 1-14 months and three other patients had primary drug resistance. Our results suggest that cytogenetic analysis after stimulation of cultures by cytokines detects clonal abnormalities in 40-50% of newly diagnosed myeloma patients and that these patients often have a short survival and/or primary drug resistance.

Bone Marrow↗
PubMed1993

Philadelphia negative, BCR-ABL positive adult acute lymphoblastic leukemia (ALL) in 2 of 39 patients with combined cytogenetic and molecular analysis.

We performed cytogenetic and molecular analysis of the BCR-ABL rearrangement by polymerase chain reaction (PCR) in 39 consecutive cases of adult acute lymphoblastic leukemia (ALL). Eleven patients had a Philadelphia (Ph) chromosome. Thirteen patients had a BCR-ABL rearrangement, involving minor breakpoint cluster region (m-bcr, situated in intron 1 of the BCR gene) in 11 cases, and major breakpoint cluster region (M-bcr, 'specific' of chronic myeloid leukemia) in the remaining two cases. All of the 12 BCR-ABL cases studied immunologically were of early B, CALLA-positive immunophenotype. The 13 BCR-ABL positive cases included the 11 Ph-positive cases, and two patients with normal karyotype at diagnosis. In the two Ph-negative BCR-positive cases, seven (patient 1) and 18 (patient 2) mitoses had been examined at diagnosis. In patient 1, Ph negativity at diagnosis could certainly be explained by the small number of mitoses analyzed, as a Ph chromosome was found at relapse. This was less probable in patient 2, who raised the issue of whether authentic Ph-negative BCR-ABL-positive ALL exists (as in the chronic myeloid leukemia model) or not. Whatever the explanation, our results suggest that molecular detection of BCR-ABL should be more widely used in B-lineage ALL.

Adult↗
PubMed1992

Decreased expression of eosinophil peroxidase and major basic protein messenger RNAs during eosinophil maturation.

We evaluated the levels of mRNAs encoding cationic proteins in peripheral blood eosinophils (PBE) purified from patients with eosinophilia and in eosinophils differentiated from cord blood cells (CBC) by culture with recombinant human interleukin-3 (rhIL-3), rhGM-CSF, and rhIL-5. Messenger RNAs encoding eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) were detected by Northern blot hybridization with the respective specific oligonucleotide probes. In mature PBE, MBP mRNA appeared to be absent, whereas EPO mRNA was barely detectable in only 5 of the 19 patients. In contrast, EDN and ECP mRNAs were observed in the PBE of all patients. In CE, EPO, and MBP, mRNAs were abundant in immature eosinophils and their amounts decreased after differentiation toward eosinophils. ECP and EDN mRNAs followed the same patterns, but mRNAs were less abundant at all timepoints studied. Study of mRNA t1/2 during the time course of differentiation indicated that changes in the stability of the different mRNAs were not responsible for the variations observed in the steady-state levels. Together, these results suggest that regulation of expression differs among EPO, MBP, EDN, and ECP mRNAs during the time course of eosinophil differentiation.

Actins↗
PubMed1992

Acute monocytic leukemia with (8;22)(p11;q13) translocation. Involvement of 8p11 as in classical t(8;16)(p11;p13).

A new case of acute monocytic leukemia observed in a 73-year-old male (ANLLM5) with an unusual t(8;22)(p11;q13) is reported. The blasts did not demonstrate erythrophagocytosis, but the presence of both naphthol-ASD-chloro-acetate esterase and butyrate esterase activities was similar to that seen in cases with t(8;16)(p11;p13). Involvement of the 8p11 region in ANLLM4 and M5 is discussed, being the third most frequent rearrangement in acute leukemia with monocytic components seen at our Center.

Aged↗
PubMed1992

Rare occurrence of P53 gene mutations in multiple myeloma.

We looked for mutations of exons 5-8 of the P53 gene in bone marrow cell from 37 cases of multiple myeloma, using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and DNA sequencing. 25 patients also had cytogenetic analysis. A point mutation, leading to an amino acid change in the P53 protein was found in only one case, involving exon 5. These findings suggest that P53 mutations are very rare in multiple myeloma, and that this disease may be categorized among the few neoplasms where P53 abnormalities have very limited role, if any.

Base Sequence↗
PubMed1992

Levels of soluble IL-2 receptor in plasma from asthmatics. Correlations with blood eosinophilia, lung function, and corticosteroid therapy.

Evidence now suggests that eosinophils and T lymphocytes infiltrating bronchial tissues may play a key role in the pathophysiology of asthma. Circulating eosinophils, lung function, and plasma soluble IL-2 receptor (sIL-2R) were measured in 42 asthmatic patients referred for symptomatic asthma. The patients were divided into two groups based on the presence or absence of atopy. The group of non-atopic asthmatics was further divided according to the patients' requirement for long term oral corticosteroids. The mean sIL-2R +/- s.d. was 36.3 +/- 9.9 pM in the control group, 28.9 +/- 9.2 pM in the atopic asthmatics, 43.3 +/- 18.07 pM in the non-atopic asthmatics without oral steroid therapy, but was increased in the steroid-treated group (62.2 +/- 19.3 pM, P less than 0.01). A significant correlation was found between FEV1 and circulating eosinophils in atopic asthmatics and in non-atopic asthmatics without oral corticosteroid therapy, but not in the steroid-treated group. Furthermore, significant correlations were found between sIL-2R and FEV1, and between sIL-2R and blood eosinophils, in the group of non-atopic asthmatics not on oral steroid therapy. No such correlations were evidenced in the other groups of asthmatics. Similar results were obtained during the clinical course of three non-atopic patients followed for more than 1 year. These data suggest that T cell activation appears more prominent in non-atopic asthma than in atopic asthma. Moreover, it appears that T cell activation can occur in severe forms of asthma despite steroid treatment. Finally, the results suggest a possible link between T cell activation, eosinophils, and lung function, which may reflect a particular pathogenetic mechanism involved in non-atopic asthma.

Adrenal Cortex Hormones↗
PubMed1991

Usefulness of electron microscopy in the diagnosis of congenital dyserythropoietic anemia type I: report of a case.

This report describes a case of congenital dyserythropoietic anemia (CDA) type I diagnosed in a 22-year-old woman with a two year history of macrocytic anemia. Light microscopy study of bone marrow disclosed only minor and nonspecific findings, without erythroid hyperplasia. Electron microscopy of bone marrow erythroblasts surprisingly showed most of the classical features of CDA type I. Electron microscopy may be an important tool for the diagnosis of macrocytic anemia of obscure origin, especially in young patients.

Adult↗
PubMed1990

Translocations (5;17) and (7;17) in patients with de novo or therapy-related myelodysplastic syndromes or acute nonlymphocytic leukemia. A possible association with acquired pseudo-Pelger-Huët anomaly and small vacuolated granulocytes.

Twelve patients [two with de novo myelodysplastic syndrome (MDS), four with secondary MDS, five with de novo acute nonlymphocytic leukemia (ANLL), one with secondary ANLL] showed a 17p deletion resulting from translocations involving 17p: t(5;17)(p11;p11) in four cases, t(7;17)(p11;p11) in six cases, complex (5;17)(q23;p12) translocation with dicentric chromosome in one case, and t(17;?)(p11-12;?) in the remaining patient. All these structural anomalies were observed in hypodiploid clones associated with total or partial monosomy of chromosomes 5 and 7 (12 cases), monosomy 12 (five cases), monosomy 3 (four cases), and monosomy 4 (three cases). Median survival was only 3.3 months (range 3 days to 8 months). Striking features were observed in bone marrow mature granulocytes: all but one case had a pseudo-Pelger-Huët anomaly in a significant number of granulocytes, and eight patients had granulocytes with reduced size and clear cytoplasmic vacuoles. Careful cytological review of 51 patients with MDS or ANLL and various cytogenetic anomalies was performed for comparison: vacuolated granulocytes were a very uncommon finding. On the other hand, eight patients had a pseudo-Pelger-Huët anomaly, which correlated significantly with total monosomy 17 in these patients. A possible correlation between cytological anomalies and cytogenetic data is discussed, and the role of 17p in the nuclear segmentation of granulocytes is stressed.

Adult↗
PubMed1990

Prognostic value of dysmyelopoietic features in de novo acute myeloid leukaemia: a report on 132 patients.

The prognostic value of cytological features was assessed in 132 patients with de novo acute myeloid leukaemia (AML) treated by anthracycline-cytosine-arabinoside combination chemotherapy. Of these patients, 98 (75%) achieved complete remission (CR). A significantly lower CR rate was seen in patients with trilineage dysmyelopoiesis (TDMP) (P = 0.003), but not in patients with dyserythropoiesis and/or dysgranulopoiesis without abnormal megakaryocytes. Other unfavourable factors were age greater than 50 years (P = 0.042), leucocyte count greater than 100 x 10(9)/l (P = 0.006), M5 FAB subtype (P = 0.013), presence of complex cytogenetic rearrangement or abnormalities of chromosome 5 and/or 7 (P = 0.001). Bone marrow eosinophilia greater than 3% was significantly associated with a higher CR rate (P = 0.04). In a multivariate analysis, a low CR rate was best predicted by the presence of a complex karyotype or abnormalities of chromosome 5 and/or 7 (P = 0.0001) and by the TDMP (P = 0.0036). Median actuarial disease-free survival (DFS) was 24 months. Actuarial DFS was significantly shorter in patients with TDMP (P = 0.0001) and an elevated leucocyte count (P = 0.02). Age, FAB subtype and karyotype had no significant incidence on DFS. Presence of TDMP appears to be an important prognostic factor in de novo AML. This could be used as one of the guidelines to therapy.

Adolescent↗
PubMed1989

Burkitt cell acute leukaemia (L3 ALL) in adults: a report of 18 cases.

Between 1981 and 1987, L3 ALL was diagnosed in 18 adult patients, with a median age of 26 (range 16-66) and M/F ratio of 3.5. At diagnosis, 11 patients had splenomegaly, 11 had enlarged lymph nodes, and 15 patients had central nervous system (CNS) disease, of whom 10 had mental neuropathy. Anaemia was found in 13 patients, thrombocytopenia in 17 and the median white cell count was 25.5 x 10(9)/I (range 8.6-89). Surface immunoglobulins were found on the blasts of every patient. Seventeen patients had a t(8;14) (q24;q32) translocation. One had an apparently normal karyotype, but only six mitoses could be examined. During the period of the study different treatment protocols, which comprised increasingly intensive systemic and CNS chemotherapy, were used. Six patients died less than 3 weeks after admission, two of them of acute tumour lysis syndrome and two of CNS haemorrhage. In two other patients, rapid progression of CNS leukaemia was seen in spite of the treatment. Ten patients (56%) achieved complete remission (CR). Two were allografted and two were autografted early in CR. Four patients relapsed, three of the four relapses involving the CNS. A median actuarial disease-free survival was not attained, and a plateau was achieved at 57% after 7 months, with no later relapse. Median actuarial survival of the 18 patients was only 6 months, but a plateau was obtained at 31% after 11 months. Prognosis seemed related to the intensity of chemotherapy: recent patients, treated more aggressively, achieved CR more often than earlier patients, treated with less intensive protocols, although the number of patients was too small to draw any firm conclusion. The initial white cell count was also a prognostic factor, as none of the patients with more than 30 x 10(9)/I leucocytes achieved CR. Our results suggest that the outcome of adult L3 ALL can be improved, as in children, by increased intensity of treatment, particularly with regard to CNS leukaemia therapy. Early deaths are still frequent, however, but their incidence can probably be reduced by better prevention and early management of the acute tumour lysis syndrome.

Adolescent↗