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Biomedical subjects

A Brizard

Publications and source records attributed to A Brizard.

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

Trisomy 8q due to i(8q) or der(8) t(8;8) is a frequent lesion in T-prolymphocytic leukaemia: four new cases and a review of the literature.

Cytogenetic abnormalities found in four cases of T-cell prolymphocytic leukaemia (T-PLL) are described. An isochromosome 8q was found in three patients and a t(8;8) in one. In the four cases, karyotypes were complex and showed a high degree of instability. In addition, we reviewed 27 published cases of cytogenetically studied T-PLL. On the whole, the most frequently recurring anomalies in T-PLL are 14q lesions with nonrandom breakpoints, inversion (14)(q11q32) or tandem translocations (14;14) (not seen in any of our cases) and trisomy for 8q. mainly due to i(8q), found in more than 40% of patients each. Similar structural anomalies were found almost as frequently among the 23 cytogenetically studied cases of so-called T-chronic lymphocytic leukaemia (T-CLL) reported prior to 1989. It is now accepted that the T-cell counterpart of B-CLL either does not exist or is exceedingly rare and thus previously reported cases of T-CLL sharing the chromosomal characteristics of T-PLL may well have been misdiagnosed examples of T-PLL. Isochromosomes 8q are exceptionally found in other types of haematological malignancies. However, i(8q) could not be shown to be the primary lesion in any case in T-PLL and the role of trisomy for 8q, as well of the associated monosomy 8p, is entirely unknown.

Adult↗
PubMed1994

Proliferative response of B chronic lymphocytic leukemia lymphocytes stimulated with IL2 and soluble CD23.

The in vitro proliferative response of purified B-chronic lymphocytic leukemia (B-CLL) lymphocytes cultured in the presence of soluble CD23 (sCD23) with or without IL2 was compared to the responses induced by phorbol 12-myristate 13-acetate (PMA), Staphylococcus aureus strain Cowan I (SAC), IL1, IL2, IL4, IL6 and the combination of IL2 and interferon (IFN) alpha or IFN gamma. As expected, B-CLL lymphocytes proliferated with PMA, SAC and IL2 with a clear enhancement of the IL2-induced response by IFN alpha or IFN gamma. They failed to proliferate in response to sCD23, IL1, IL4 or IL6 alone nor to the combinations of sCD23 and any of the 3 latter cytokines. However, sCD23 significantly increased the proliferation of B-CLL cells induced by IL2, suggesting a protective effect of sCD23 on apoptosis. Serum levels of sCD23 and CD23 membrane expression were high in every patient which is compatible with the hypothesis of an autocrine or paracrine activation loop. Detectable CD23 expression was lost in all cultures except for that stimulated by PMA. Only supernatants of PMA-stimulated cultures contained high sCD23 levels.

Adult↗
PubMed1994

Unclassifiable high grade malignant T-cell lymphoma with clonal evolution.

We report a case of leukemic malignant T-cell lymphoma with mixed small and large cells. The small cells displayed a mature CD8-positive phenotype, a diploid DNA distribution by cell cycle analysis, and structural karyotypic abnormalities. Large cells were near triploid, showed additional structural cytogenetic abnormalities and a more immature membrane phenotype without CD8 expression. Altogether, these data provide suggestive evidence for a clonal evolution from a mature small cell T-cell lymphoma to a more immature large cell proliferation.

Aged↗
PubMed1994

Effects of alpha-interferon on MHC unrestricted cytotoxicity in chronic myelogenous leukemia.

The capacity of alpha-interferon (alpha-IFN) to induce lymphokine activated killer (LAK) cytotoxicity in the absence of interleukin-2 (IL2) has prompted us to test whether its ability to reduce dramatically the number of Ph1+ clones in chronic myelogenous leukemia (CML) patients is in part mediated through the generation of natural killer (NK) or LAK activity. The latter were tested using NK-sensitive (K562) and NK-resistant (Raji) cell lines in a target-cell colony-growth inhibition assay. Effector cells (E) were patient blood mononuclear cells (MC) without in vitro activation prior to their coculture with targets (T). Here we report that cytogenetic remission in alpha-IFN-treated patients is associated with significantly enhanced NK and LAK activities. Nevertheless, some patients under alpha-IFN therapy were found to develop lymphoid blast crisis despite high levels of NK and LAK activities, and partial or total cytogenetic remission. In contrast, most of the patients who developed nonlymphoid blast crisis presented 100% Ph1+ cells and displayed defective NK and/or LAK activity. These observations could favor the hypothesis that there is an indirect but complex effect of alpha-IFN on leukemic cells, mediated by cells involved in immune surveillance; and also that lymphoid blast cells may actually escape LAK cytotoxicity.

Adolescent↗
PubMed1994

Molecular remission after allogeneic bone marrow transplantation for chronic lymphocytic leukemia.

A 51-year-old man with previously treated CLL received an allogeneic sex mismatched BMT after total body irradiation and high dose chemotherapy. Residual disease was studied at phenotypic and molecular levels including Y chromosome DNA amplification by PCR assay. The patient was clinically disease-free 20 months after BMT with disappearance of the leukemic clone assessed by the most sensitive methods of detection. Long-term follow-up is necessary to ascertain the relevance of Y DNA amplification in predicting outcome in this patient.

Antineoplastic Agents↗
PubMed1994

Detection of monosomy 7 and trisomies 8 and 11 in myelodysplastic disorders by interphase fluorescent in situ hybridization. Comparison with acute non-lymphocytic leukemias.

Cells from 50 patients with myelodysplastic syndrome (MDS) and 20 patients with acute non-lymphoblastic leukemia (ANLL) were studied by fluorescent in situ hybridization (FISH) using alphoid biotinylated probes to detect numerical chromosome 7, 8 and 11 aberrations in interphase nuclei. FISH data were compared with cytogenetic results. Both methods were in agreement in 25/50 MDS and 20/20 ANLL cases. Trisomy 11 was found neither by cytogenetic study nor by FISH. In 11 MDS patients the percentage of abnormal cells was higher by FISH than by classical cytogenetic analysis. FISH revealed monosomy 7 which was undetectable by karyotypic study in 5-22% cells from 15 MDS patients. It also allowed the identification of two small markers and a ring chromosome in two MDS cases. FISH hence appears to be useful for the detection of minor abnormal clones and is a convenient complement to conventional cytogenetic analysis in the study of MDS.

Aged↗
PubMed1993

Effects of sCD23 on proliferation of leukemic cells from a patient with chronic myelogenous leukemia during blast crisis.

The present study has attempted to further delineate the growth factor requirements of peripheral blasts of a patient with CML in acute phase. Phenotypic analysis of leukemic blasts from this patient before culture has shown a homogenous population of CD34+ cells at the onset of blast crisis. In the second and third samples the percentage of CD34+ DR+ blast cells decreased slightly and up to 32% of cells in the third sample expressed the CD19 antigen. Optimal proliferation of cells derived from the first sample required the presence of exogenous sCD23 and to a lesser extent IL7. The stimulatory effects of sCD23 and IL7 were clearly reduced 4 months later and no longer detected after 6 months. This variability in growth factor response along with disease progression may be related to phenotypic differentiation. There was no evidence for lymphoid or myeloid maturation after 4 days of liquid culture. Our results in conjunction with previous studies are in agreement with sCD23-involvement in the complex control of proliferative processes at both normal and leukemic stages, demonstrating that cytokines are critical in determining CML cell proliferation.

Acute-Phase Reaction↗
PubMed1993

Complete variable region deletion in a mu heavy chain disease protein (ROUL). Correlation with light chain secretion.

In a patient affected with chronic lymphocytic leukemia with lymphocyte surface mu and kappa determinants and vacuolated bone marrow plasma cells, the serum contained polymers of a truncated mu chain and normal-sized kappa chains. These light chains were present as monomers and covalent dimers in studies performed under dissociating conditions, but they were linked by non-covalent bridges to a portion of the serum short mu chains. The patient's urine contained a kappa type Bence-Jones protein. Study of a messenger RNA and complementary DNA from blood cells showed the abnormal mu chain to lack the entire variable region, likely due to a direct splicing of the leader peptide exon onto the CH1 exon. The production of light chains, a rare event in heavy chain diseases, appears to correlate with the occurrence of a heavy chain deletion restricted to the variable domain, likely because the non-covalently linked light chains allow these unusual heavy chains to be secreted.

Amino Acid Sequence↗
PubMed1993

Hematopoietic progenitor content of fetal cord blood collected using citrate-phosphate-dextrose: influence of holding temperature and delays.

Storage of unseparated fetal cord blood collected into citrate-phosphate-dextrose (CPD) for 48 hours has been studied using progenitor cell assays [plasma clot technique with plasma-conditioned medium, erythropoietin (EPO), erythropoietin + IL-3 as growth factors]; collected fetal blood volume was low [61 +/- 4 ml, mean +/- 95% confidence interval (CI)]. The CFU-GM concentration in total cord blood was 2460 +/- 1476 CFU-GM/ml, comparable to normal bone marrow collected into medium RPMI + heparin (2350 +/- 1258); 2 of 12 samples contained fewer than 10(3) CFU-GM. Storage of unseparated cord blood CFU-GM in CPD was better at 4 degrees C (rapid decrease at day (D) 2 from 15 +/- 9 x 10(4) at D0; 14 +/- 11 x 10(4) at D1 to 6 +/- 4 x 10(4) at (D2) than at 22 degrees C (strong decrease since D1: 5 +/- 4 x 10(4) CFU-GM). The CFU-GEMM content remained steady at 4 degrees C: from 16 +/- 16 x 10(4) at D0 to 18 +/- 16 at D2. Cryopreservation and thawing of unfractionated cord blood at D0 did not affect the CFU-FM cloning rates. Whether mature progenitors are more affected than stem cells by storage in CPD remains to be determined.

Adult↗
PubMed1993

Endogenous lymphokine activated killer cell activity and cytogenetic response in chronic myelogenous leukaemia treated with alpha-interferon.

The capacity of alpha-interferon (alpha-IFN) to induce lymphokine activated killer (LAK) cytotoxicity in the absence of interleukin-2 (IL2) has prompted us to test whether or not its ability to reduce dramatically the number of Ph1+ clones in chronic myelogenous leukaemia (CML) patients is in part mediated through the generation of natural killer (NK) or LAK activity. The latter were tested using NK-sensitive (K562) and NK-resistant (Raji) cell lines in a target-cell colony-growth inhibition assay. Effector cells (E) were patient blood mononuclear cells (MC) without in vitro activation prior to their coculture with targets (T). Out of 16 patients tested so far, three failed to undergo cytogenetic remission under alpha-IFN therapy. No NK nor LAK cells could be detected in the MC from two of them while the other displayed NK activity within upper normal limits. 13 patients underwent complete (eight) or partial (five) cytogenetic remission together with significantly high NK and/or LAK activity as compared to normal controls. These observations could favour the hypothesis of an indirect effect of alpha-IFN on leukaemic cells, mediated by cells involved in immune surveillance.

Adolescent↗
PubMed1993

Chromosomal analysis of purified B-chronic lymphocytic leukemia lymphocyte cultures: comparison with whole blood cultures and in situ hybridization.

Chromosomal analysis of stimulated whole blood cells and purified B lymphocytes was performed in 13 stage A(0) and 1 stage C(IV) chronic lymphocytic leukemia (B-CLL) patients. Abnormal clones were found in 6 cases in purified B lymphocytes cultures and in a single one in whole blood cultures. In situ hybridization with a chromosome 12 probe was in accordance with the chromosomal analysis of purified B-CLL lymphocytes and not with the results obtained using whole blood culture. Cytogenetic analysis of isolated B cells is simple and sensitive. It enhances the detection of abnormal clones in B-CLL and applied to larger series of patients, it should allow a precise evaluation of the incidence of chromosomal abnormalities in CLL and of their clinical (prognostic) significance.

Aged↗
PubMed1993

Cytogenetic heterogeneity in t(11;19) acute leukemia: clinical, hematological and cytogenetic analyses of 48 patients--updated published cases and 16 new observations.

We report on 16 cases of t(11;19) acute leukemia and review data of published observations: altogether updated data of 48 patients are analyzed. Four hematological groups could be distinguished: (i) 13 cases of acute lymphoblastic leukemia (ALL) of B lineage, mostly CD19+; (ii) eight cases of biphenotypic leukemia: CD19+ (most often) ALL but with simultaneous or inducible expression of differentiation marker of monocytic lineage. The B lineage and biphenotypic leukemias were predominantly found in female infants; (iii) four cases of T-ALL in children; and (iv) 23 acute non-lymphocytic leukemia (ANLL) cases generally of M4 or M5 subtype, predominantly in males. Cytogenetically, at least two subtypes were observed with possibly an identical breakpoint on 11q23 but discrete breakpoints on 19p: lymphoid, biphenotypic, and most congenital myeloid cases showed a distal breakpoint on 19p13 producing 11q- and 19p+ derivatives, while most older myeloid cases showed 11q+ and 19p- derivatives as a result of a more proximal breakpoint on 19p12 or p13.1. The latter type was clearly detected using R bands but barely visible using Q or G bands while the other translocation was easy to detect with G bands but could be missed with R bands. The white blood cell count is usually high in these t(11;19) acute leukemias and prognosis is poor, except for T-ALL cases.

Adolescent↗
PubMed1993

Improvement of cytogenetic results in B-cell chronic lymphocytic leukemia using immuno-purified leukemic cells.

Cytogenetics of purified B lymphocytes and whole blood cultures were studied in 14 patients with B-CLL and fluorescence in situ hybridization (FISH) was performed on interphase cells in 12 of these cases in order to detect trisomy 12. Only one minor abnormal clone was found on whole blood cell cultures, clonal anomalies were found in a large proportion of mitoses of 6/14 cultures of purified B cells. FISH detected a trisomy 12 in a case, not found in whole blood cultures but found in 78% metaphases of cultures of purified B lymphocyte. This method may be as sensitive as FISH for the detection of trisomy 12 and improves the detection of clonal abnormalities in CLL.

Adult↗
PubMed1992

Simultaneous injection of hepatitis B vaccine with BCG and killed poliovirus vaccine.

In most developing countries, hepatitis B virus is endemic and prevention has to be carried out early in life and on a mass scale. In these regions, simultaneous administration of multiple antigens is normal practice. We have therefore investigated the interaction of hepatitis B vaccine with BCG and inactivated polio vaccine. The serological antibody response to poliovirus and HBsAg as well as the cellular immune response to tuberculin post BCG immunization were assessed. The immune responses to HBsAg, BCG and polio vaccines injected simultaneously were comparable to those observed after separate administration of each vaccine. Moreover, no increase of adverse reactions was noted. Results confirmed that HB vaccine could be introduced into the WHO expanded programmes on immunization without impairing the expected protective efficacy against the targeted vaccine-preventable diseases.

BCG Vaccine↗