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A Bardi

Publications and source records attributed to A Bardi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cytogenetic and interphase cytogenetic characterization of atypical chronic lymphocytic leukemia carrying BCL1 translocation.

Conventional chromosome analysis (CCA) and fluorescent in situ hybridization (FISH) studies, using a 390-kb yeast artificial chromosome probe spanning the area of multiple breakpoints of the BCL1 locus at 11q13, were performed on 57 patients fulfilling the French-American-British criteria for the diagnosis of atypical B-cell chronic lymphocytic leukemia (CLL). To better define the incidence of 13q deletions and trisomy 12, FISH analysis was also performed using a cosmid probe that recognized a DNA sequence between the Rb gene and the D13S25 locus at band 13q14 and a chromosome 12-specific pericentromeric probe. All patients were characterized by cytoimmunological and hematological studies. Fourteen cases displayed three fluorescent signals in 41-98% interphase cells when hybridized to the BCL1 yeast artificial chromosome probe, documenting the presence of BCL1 translocation (BCL1-positive cases). The presence of t(11;14)(q13;q32) was ascertained in 12 cases using CCA and by dual color interphase FISH using the BCLI probe and a 14q telomere probe in 2 karyotypically normal cases. The remaining 43 cases had two signals in more than 95% interphase cells (BCL1-negative) and did not have the t(11;14) at CCA. Although 13q14 deletions were seen by means of CCA in only 5 of 14 BCL1-positive cases, hemizygous or homozygous deletions at band 13q14 were detected by FISH in 11 of 14 BCL1-positive cases, as compared with 17 of 43 BCL1-negative cases (P = 0.01). A subclone with trisomy 12 in addition to BCL1 translocation and del(13q14) was present in four BCL1-positive cases. We arrived at the following conclusions: (a) FISH with this BCL1 YAC probe is an efficient method for the detection of the t(11;14) and of the corresponding involvement of the BCL1 locus in this lymphoproliferative disorder; (b) the majority of BCL1-positive atypical CLLs by French-American-British criteria may carry 13q14 deletions; (c) the recognition of this cytogenetic subset of atypical CLL, sharing some immunological and cytogenetic features with mantle cell lymphoma, may be important, because these patients usually present isolated peripheral blood and marrow lymphocytosis, with or without mild to moderate spleen involvement, and may require early cytotoxic treatment.

Chromosomes, Artificial, Yeast↗
PubMed1997

Flow cytometry measurement of GM-CSF receptors in acute leukemic blasts, and normal hemopoietic cells.

A quantitative analysis of expression levels of GM-CSF receptors was performed by flow cytometry in different disease categories, ie AML (n = 72), ALL (n = 18), and MDS (n = 12), as well as 12 healthy volunteers, using three different unconjugated GM-CSF/R monoclonal antibodies (McAbs) (HGM-CSFR (CD116), M5D12, 4B5F5), and appropriate standards. By using the reference HGM-CSFR McAb, in healthy subjects we found detectable levels of GM-CSF/R on blood monocytes (mean MESF (molecules of equivalent soluble fluorochrome)/cell: 36.1 x 10[3]), neutrophils (mean MESF/cell: 7.4 x 10[3]), bone marrow (BM) myelo-monocytic precursors (MESF range for the myeloid component, ie promyelocytes, myelocytes, metamyelocytes: 11.7-40.5 x 10[3], and for the monocytic lineage: 25.7-69.2 x 10[3]), and in two distinct subsets of BM CD34+ progenitor cells (GM-CSF/R dim: 2.5 x 10[3] MESF/cell, GM-CSF/R bright (10% of the total number of CD34 cells: 22.0 x 10[3] MESF/cell). In these subjects, there was no correlation between the expression levels of GM-CSF/R and CFU (CFU-GM, CFU-GEMM, BFU-E) colony production. Among the AML samples, M5D12 McAb was positive in 33%, 4B5F5 McAb in 90%, and HGM-CSF/R McAb in 78% of the cases examined (range of MESF/cell for the HGM-CSFR McAb: 0.9 x 10[3]-106.7 x 10[3]). The highest MESF values were seen in the M5 FAB subvariety (mean: 39.4 x 10[3]), where all the patients tested (n = 20) showed a strong positivity for the HGM-CSFR McAb. On the contrary, all ALL samples were GM-CSF/R negative except in two patients, who displayed a dim GM-CSF/R positivity (My+ALL: 1.3 x 10[3] MESF/cell; pro-B ALL: 1.0 x 10[3] MESF/cell). In most (>70%) M1 FAB subtypes, GM-CSF/R+ blasts co-expressed CD34low, HLA-DRhigh, CD33, CD38 antigens, and had little or no capacity to form CFU-GM colonies. GM-CSF/R+ blasts from the M5 FAB category were also positive for CD14, CD11c, CD33 and CD87. Furthermore, the number of GM-CSF/R expressed by leukemic cells from five out of 72 (7%) AML patients was above the highest values seen in normal samples (>69.2 x 10[3] MESF/cell), allowing the possibility of using this marker for the monitoring of the minimal residual disease (MRD) in a subset of AML. Cell culture studies aimed at evaluating GM-CSF receptor modulation following AML blast exposure to rhGM-CSF showed two distinct patterns of response; in the first group (6/10 cases) rhGM-CSF down-modulated GM-CSF receptors, whereas in the second group (4/10 cases), rhGM-CSF treatment was associated with either an increase or no change in the number of GM-CSF/R. In conclusion, cellular GM-CSF/R expression was variable and ranged from undetectable (ALL and a minority of AML) to very high intensities in M5 AML, and were also documented in some M0 AML, thus suggesting the concept that GM-CSF/R detection may be of help in lineage assignment of undifferentiated forms. Since the number of GM-CSF/R on AML blasts may be modulated after GM-CSF treatment, it can be postulated that the clinical use of GM-CSF in this disease may be optimized by a dynamic analysis of the number and the affinity status of GM-CSF-R in blasts and normal hemopoietic cells.

Acute Disease↗
PubMed1997

Chromosome aberrations in atypical chronic lymphocytic leukemia: a cytogenetic and interphase cytogenetic study.

To define better the chromosomal profile of atypical chronic lymphocytic leukemia (aCLL), cytogenetic and interphase cytogenetic studies were performed in 43 cases, using mitogen-stimulated cultures and DNA probes detecting the two most frequently occurring aberrations in CLL, ie +12 and 13q14 deletions. All cases showed monoclonal CD5/CD19-positive lymphocytosis, with more than 10% large lymphocytes and/or prolymphocytes in peripheral blood smears and reactivity with FMC7, or bright expression of surface immunoglobulins in a fraction of the cases. Karyotype aberrations were detected in 27 of 43 cases (62.8%). Recurrent chromosome changes were +12 (nine cases), 13q14 aberrations (five cases), 11q anomalies (three cases), 6q21-q23 abnormalities and 4q anomalies with different breakpoints (two cases each). Additional chromosome changes were seen in four cases with +12, in three cases with 13q14 anomalies, in two cases with 11q anomalies, in one case with 6q and 4q anomalies. Trisomy 12 was associated with 13q14 anomalies in three cases, one of which also had an 11q abnormality; other associations, found in one case each, were: 13q14 deletion with a 6q anomaly, 11q anomaly with 13q- and 7q-, a 6q anomaly with 7q- and +12. Interphase cytogenetics confirmed the results of chromosome banding analysis and showed that six patients with normal karyotype or no mitosis in fact had concomitant +12 and 13q14 deletion in four cases and isolated +12 or 13q14 deletion in one case each, with a resultant 76% overall incidence of cytogenetic abnormalities. The presence of +12, 13q14 deletions, 11q, and 6q21-q23 anomalies in 19 cases was associated with a 2-month median interval between diagnosis and start of treatment, as compared with a 24-month median interval in 14 cases with normal karyotype or non-recurrent chromosome changes (P = 0.003). We conclude that aCLL is characterized by a relatively high incidence of chromosome anomalies, with recurrent chromosome changes, involving chromosomes 12, 13q14, 6q21q23, 11q, and, possibly, 4q. The presence of complex karyotypes, with concomitant abnormalities of 13q, +12, 6q, 11q, suggests that the development of sequential chromosome changes, rather than any single specific anomaly, may underlie leukemogenesis in this cytologic subset of CLL, partially accounting for the relatively aggressive clinical course.

Adult↗
PubMed1996

Interleukin-3 plus interleukin-6 may improve chromosomal analysis of multiple myeloma: cytologic and cytogenetic evidence in thirty-four patients.

To better define the role of interleukin-3 (IL-3) and IL-6 in the cytogenetic analysis of multiple myeloma (MM), we performed concomitant chromosome and cytologic studies in 34 patients. In each case, 10-30 x 10(6) bone marrow cells were incubated in two independent cultures consisting of conventional cytogenetic medium with and without IL-3 plus IL-6 added for 72 hours. 1-ml aliquots of each culture were aspirated at 24, 48, and 72 hours and exposed to colcemid for 6 hours. Cytospin preparations were then made and mitotic cells were counted and identified as plasma cells or as nonmalignant cells based on their reactivity with an appropriate anti kappa/lambda serum. Slides for conventional cytogenetic analysis were prepared at 72 hours. A greater than two-fold increase of mitotic plasma cells was observed in cytospin preparations from stimulated cultures versus unstimulated cultures in 15 of 34 cases, whereas a less than 2-fold increase, no variation or no mitosis was recorded in 19 cases. Comparison of the number of mitotic plasma cells in stimulated cultures at 24, 48, and 72 hours showed a decreased mitotic activity at 72 hours. Clonal abnormalities were detected by conventional cytogenetic analysis in 19 of 34 cases (55.8%). Recurrent clonal aberrations involved chromosome 13 (4 cases), chromosomes 1p, and 14q (3 cases); chromosomes 3p, 6q, 7q, and 9q (2 cases). We conclude that IL-3 + IL-6 may increase the number of dividing plasma cells in cytogenetic cultures and that a 2-day culture with these cytokines may facilitate the detection of chromosome abnormalities in MM.

Bone Marrow↗
PubMed1995

Heterogeneity of lineage involvement by trisomy 8 in myelodysplastic syndrome. A multiparameter analysis combining conventional cytogenetics, DNA in situ hybridization, and bone marrow culture studies.

To better understand the role of trisomy 8 in myelodysplastic syndrome (MDS), we performed a multiparameter analysis combining conventional chromosome studies (CCS), fluorescence in situ hybridization (FISH), and bone marrow (BM) culture studies in two patients with MDS evolving into acute myeloid leukemia (AML). A mosaicism of a cytogenetically normal clone and a clone with trisomy 8 was detected in both patients throughout the course of the disease, a finding confirmed by FISH on BM cells. The relative size of the trisomic clone increased from 52% to 71% (p < 0.0001) and from 53% to 69% (p = 0.001) of all BM cells at the time of the leukemic switch in patients 1 and 2, respectively. Combined FISH and immunophenotyping of BM cells showed involvement of the granulomonocytic lineage in patient 1 and involvement of erythroid cells as well as of the granulomonocytic lineage in patient 2. Only disomic lymphocytes were detected in both patients. FISH on single hemopoietic colonies grown in semisolid media detected trisomic CFU-GM and disomic BFU-E in patient 1, whereas a proportion of CFU-GM and BFU-E deriving from the trisomic clone was detected in patient 2. However, the percent of trisomic colonies was lower than the percent of involved granulomonocyte precursors and involved erythroblasts, as detected by combined FISH and immunophenotyping on fresh BM samples. We have thus shown heterogeneity of lineage involvement by trisomy 8 in MDS undergoing transformation into AML. Although preferential growth of disomic clones may occur in vitro, the finding of an increased size of the trisomic clone at the time of leukemic switch suggests that these cells had proliferative advantage in vivo over cells without trisomy 8.

Aged↗
PubMed1995

Cytogenetics of hybrid acute leukemias.

Although the recognition of hybrid acute leukemia (HAL) is still controversial, several reports have described cytogenetic findings in these leukemias over the last 3 years. A distinct chromosomal profile appears to be associated with different immunologic subsets of HAL. The classical t(15;17), and inv(16) as well as abnormalities of the long arm of chromosome 5 and/or 7 are preferentially associated with acute myeloid leukemia (AML) with T-cell features; the t(8;21)(q22;q22), the Ph chromosome, and 11q23 rearrangements are more frequently found in AML with B-cell features; the Ph chromosome, t11q23 and 14q32 breaks without rearrangements of the immunoglobulin heavy chain gene may be associated with acute lymphoblastic leukemia (ALL) with myeloid markers. In addition, some chromosome aberrations may be encountered more frequently in acute leukemia with major phenotype deviations than in unselected cases of acute leukemia: namely the Ph chromosome, 11q23 rearrangements, and +13. These chromosome changes appear to be associated with a low complete remission (CR) rate. An association has been documented in some patients with ALL between the presence of the t(9;22) and a minor myeloid component consisting of 5-15% blast cells with myelomonocytic features, raising the possibility that a diagnosis of bilineal acute leukemia would be more appropriate in such cases. These patients appear to have a severe outcome with significantly lower CR rate than similar cases of Ph-positive ALL without a minor myeloid component.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

CD34+ leukemic cells assessed by different CD34 monoclonal antibodies.

CD34 monoclonal antibodies (McAbs) are widely used to identify and isolate hemopoietic progenitors and to classify acute and chronic leukemias. We assessed the reactivity of 17 CD34 McAbs from the 5th International Workshop on Leukocyte Differentiation Antigens with a variety of cells types: normal bone marrow hemopoietic progenitors, 10 AML, 6 ALL, 11 CML. The reactivity for these McAbs was compared with that of reference CD34 McAbs (Q-Bend 10 and 8G12). For each cell population the % of McAb binding cells, the peak channel and the mean fluorescence intensity (MFI) of the positive cells was evaluated. The peak channel, the MFI and the number of positive cells varied significantly from case to case, depending on the McAb and the type of leukemia. According to the spectrum of reactivity three groups of McAbs were defined; however, 7 McAbs do not belong to any of these subgroups. These groups were not entirely in accordance with McAb classification based on enzyme cleavage that identified three epitopes of the CD34 molecule. Some reagents were found to be more specific for AML, other for ALL, CML or normal CD34+ cells. Normal bone marrow light density cells showed a significantly higher percentage of positive cells for 43A1 and MD34.2 McAbs compared to that documented for the remaining McAbs. AML cells showed the most variable pattern of expression for the CD34 McAbs. In leukemic samples, MESF (molecular equivalents of soluble fluorochrome) values ranged from 18,200 to 322,000 and the number of binding sites per cells was 5,000-81,000.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1993

Chromosome aberrations in CD34-positive acute myeloid leukemia. Correlation with clinicopathologic features.

Morphologic, immunologic, and cytogenetic features were studied in 30 newly diagnosed patients with CD34-positive (CD34+) de novo acute myeloid leukemia (AML) in comparison with 30 patients with CD34-negative (CD34-) AML. Karyotype at diagnosis was abnormal in 25/30 CD34+ AML patients, of which nine had major karyotype aberrations (MAKA). Clonal chromosome changes were detected in 9/30 patients with CD34- AML. The most frequent chromosome aberration in CD34+ patients was -5/5q-, an aberration showing a strong association with the M2 FAB subtype of AML. Other recurring chromosome changes involved chromosome 16q (four cases) and chromosome 17p (three cases). Total or partial monosomy 7q was detected in three cases. Among CD34- AML, two patients had the classical t(15;17) and two had structural aberrations of 6q. Among patients with CD34+ AML, nine had MAKA in association with trilineage myelodysplasia (TMDS). TMDS was infrequent in CD34+ AML without MAKA and in CD34- AML. Complete remission (CR) was achieved in 8/30 CD34+ AML (26%), as compared with 22/30 CD34- AML (73%), and median survival was 2 months in the former group and 8 months in the latter. No patient with CD34+ AML and MAKA achieved CR, whereas 8/21 CD34+ AML without complex chromosome changes or with normal karyotype achieved CR. In conclusion, a distinct cytogenetic profile may be associated with CD34+ AML. Cytogenetic findings in CD34+ AML may be clinically relevant in that they may disclose a subset of patients with MAKA with a low CR rate.

Adult↗
PubMed1991

[Validity of laparoscopy in the diagnosis of digestive system diseases].

Laparoscopy, a diagnostic procedure used in Gastroenterology, Surgery and Gynecology is a safe and effective method allowing direct vision of the contents of the abdominal cavity. Since the introduction of different imaging techniques, indications of laparoscopy have decreased. However, it is still useful in the evaluation of peritoneal diseases, liver disease, lymphoma and granulomatosis. The usefulness of laparoscopy is limited in the diagnosis of jaundice, cysts and abdominal masses.

Adolescent↗
PubMed1990

Cyclic guanidines: synthesis and antiplatelet activity of 4,6,7,8-tetrahydro-1H-imidazo[1,2-a]pyrazolo[3,4-d]pyrimidin-7-ones and 1,4,6,7,8,9-hexahydropyrazolo [3',4':4,5]pyrimido[2,1-c] [1,2,4]triazin-7-ones.

A series of 4,6,7,8-tetrahydro-1H-imidazo[1,2-a]pyrazolo [3,4-d]pyrimidin-7-ones (1b-n) and 1,4,6,7,8,9-hexahydropyrazolo [3',4':4,5]pyrimido [2,1-c][1,2,4]triazin-7-ones (2a-d) has been synthesized. In view of their potential anti-aggregating activity the compounds were tested in vitro for inhibitory activity towards ADP- and collagen-induced aggregation of human platelets. Among the compounds studied, 8-benzyl-1-(2,5-dichlorophenyl)-4,6,7,8-tetrahydro-1H-imidazo [1,2-a]pyrazolo[3,4-d]pyrimidin-7-one (1n) exhibited the most favorable activity. The 2,5-dichlorophenyl side chain is an important lipophilic and/or steric pharmacophore.

Adenosine Diphosphate↗
PubMed1990

Synthesis and platelet aggregation inhibitory effects of N-[(1H-pyrazol-1-yl)alkyl]benzoylamides.

A series of N-[(1H-pyrazol-1-yl)alkyl]benzoylamides was synthesized and tested in vitro for their inhibitory effects on adenosine diphosphate-, collagen-, arachidonic acid- and thrombin-induced aggregation of human platelets. Among them, N-[(1H-pyrazol-1-yl)butyl]benzoylamide (Ve) was found to have the most potent inhibitory activity. The structure-activity relationships are reported. The biological activity of the title compounds is reported in parallel with that of a known inhibitor of thromboxane A2 synthetase.

Chemical Phenomena↗
PubMed1989

4-(1H-pyrazol-1-yl)-2-butylamine derivatives as inhibitors of blood platelet aggregation.

Reaction of pyrazole and 3,5-dimethylpyrazole with methyl vinyl ketone gave 4-(1H-pyrazol-1-yl)-2-butanones which were converted to N-substituted 4-(1H-pyrazol-1-yl)-2-butylamines by reductive amination using ammonium acetate, primary or secondary amines and sodium cyanoborohydride as reducing agent. These new pyrazole derivatives were found to have an inhibitory effect on platelet aggregation in vitro.

Adenosine Diphosphate↗
PubMed1989

[Hepatic cirrhosis with refractory ascitis and changes in renal function: effects of the infusion of fresh plasma and furosemide].

An alteration of renal function may be the main factor responsible for refractoriness of ascites in cirrhotic patients. We treated 10 such patients with intravenous infusion of 600 ml fresh human plasma and 600 mg of furosemide. Two hr after infusion, a significant increase in Na and K urinary excretion, urine volume and osmolality and GFR was observed. Twenty four hr after infusion, these values were decreased but still above pre infusion levels. We conclude that plasma infusion in association to furosemide significantly improves renal function in cirrhotic patients with refractory ascites.

Ascites↗
PubMed1988

Haplotypes of thalassaemic families from the Po river delta: importance for prenatal diagnosis of beta-thalassaemia.

The beta globin haplotypes, corresponding to 50 normal and 50 thalassaemic chromosomes, were determined in 25 families from the Po river delta area who had beta thalassaemia. The haplotypes were obtained by studying the familial segregation of 6 restriction fragment length polymorphisms of the beta globin gene cluster. The results show an almost exclusive presence of 3 haplotypes linked to the beta thalassaemia chromosomes of this area: haplotype I, II and IX according to Orkin's classification. It is therefore possible that only two thalassaemic mutations are present. A wider variety of haplotypes was found to be linked to normal chromosomes. Prenatal diagnosis, by the analysis of polymorphic sites (the 6 plus one other) was possible in 92% of the cases. The probable high homogeneity of the molecular mutations makes the use of specific oligonucleotides practical and applicable to prenatal diagnosis.

Child↗
PubMed1987

[Ethyl esters of N-amidinobenzoyl aminoacids: inhibitory effect on thrombin, blood coagulation and platelet aggregation].

In a previous paper we described the synthesis and the antiproteolytic activity of N-(3- and N-(4-amidinobenzoyl)-L-amino acids. As an extension of these studies we examined the possible inhibitory effect of these compounds on thrombin, blood coagulation and platelet aggregation. Values of Ki for the binding to thrombin are independent of the nature of the amino acids side chain and superimposable with those obtained for the formation of benzamidine-thrombin adduct. These data suggest slight effect on blood coagulation. The benzamidine derivatives are more active on platelets.

Amidines↗