Prospective multicentric molecular study for poor prognosis fusion transcripts at diagnosis in adult B-lineage ALL patients: the LALA 94 experience.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
N Frenoy
Publications and source records attributed to N Frenoy.
Occurrence of gammopathies and lymphoproliferative disorders in liver transplant recipients randomized to tacrolimus (FK506)- or cyclosporine-based immunosuppression.
Lymphoproliferative disorders (LPDs) are a serious side effect of immunosuppression after liver transplantation, and the introduction on the market of a new immunosuppressive drug has been associated with an increased risk of these disorders. To compare the effect of cyclosporine A (CSA) and FK506 in a clinical setting, the incidence of monoclonal or oligoclonal gammopathies known to often precede the appearance of LPDs was evaluated. A total of 88 adult patients was analyzed, 46 were prospectively randomized to CSA and 42 to FK506 for immunosuppression. None of these patients had gammopathy before transplantation. All the patients were tested for immunoglobulin abnormalities five to nine times during a period of 1 year and then two to four times per year thereafter from December 1990 until March 1997. The same incidence of serum immunoglobulin (Ig) abnormalities was observed in both groups (13%) with a mean delay of appearance of 11.1 +/- 5.9 versus 7.6 +/- 3.6 months for CSA and FK506, respectively (P > .05). In each group, the gammopathies were transient in 3 patients and persisted in 2. The class of Ig involved was IgG, and a monoclonal component was documented in 2 patients treated with CSA and in 3 patients with FK506. One patient treated with FK506 developed an LPD localized to the lymph nodes 8 months after the occurrence of serum protein abnormalities. The lymphoproliferative lesions subsequently disappeared with the reduction of immunosuppression. In this study, an immunosuppressive regimen of FK506 has not shown an increased incidence of lymphoproliferation compared with CSA in adult liver transplant patients.
Adrenal Cortex Hormones↗
Human T-cell lymphotropic virus-1-positive T-cell leukemia/lymphoma in a child. Report of a case and review of the literature.
Adult T-cell leukemia/lymphoma is a monoclonal T-cell neoplasm associated with human T-cell lymphotropic virus-1 (HTLV-1) that occurs almost exclusively in adults. This report concerns a Romanian girl who had recurrent skin eruptions since infancy, subcutaneous tumors in childhood, and peripheral blood lymphocytosis, which initially developed at the age of 12 years. The circulating lymphocytes were of helper T-cell immunophenotype. Serologic studies demonstrated a number of HTLV-1 antigens in the child and her mother, and molecular analyses revealed monoclonal T-cell-receptor gamma gene rearrangement and detectable HTLV-1 proviral DNA. Conventional cytogenetic studies revealed a t(3;6)(q23;q27) chromosome translocation in most of the neoplastic cells. The patient initially responded well to interferon alfa therapy and showed regression of skin lesions and diminished lymphocytosis, but 4 years later, she developed massive lymphadenopathy and leukemic infiltration of the breast. At last clinical follow-up, at the age of 17 years, the patient had stable low-level peripheral lymphocytosis and subcutaneous tumors while being continuously treated with interferon alfa. Our review of the literature revealed six additional children with HTLV-1-associated T-cell leukemia/lymphoma, including one case with a similar clinical presentation and ethnic background. To our knowledge, the t(3;6)(q23;q27) translocation identified in this patient's neoplasm has not been previously reported in adult T-cell leukemia/lymphoma cases and may explain the early onset of disease. Although adult T-cell leukemia/lymphoma is rare in Romania, the identification of healthy carriers and vertical transmission raise the possibility that Romania might be an endemic region for HTLV-1 infection.
Base Sequence↗
Dehydroepiandrosterone sulfate in a long-term care aged population.
Ninety-four institutionalized subjects (mean age 82.9 years; 13 men and 81 women) were assessed for serum dehydroepiandrosterone sulfate (DHEAS) levels. The mean value was 457 ng/ml (SD = 426) in this cross-sectional study. There was a significant decrease in DHEAS levels with age. There was no difference among demented patients with Alzheimer's disease (n = 46), other dementia cases (n = 16), and other individuals (n = 32). The subjects treated for arterial hypertension had significantly lower DHEAS levels. No correlation was found between DHEAS and cortisol values. After age adjustment, no association was observed between DHEAS and chronic diseases, medications, several biochemical or hematological parameters, or 3-year mortality.
Age Factors↗
Serum dehydroepiandrosterone sulfate levels as an individual marker.
To assess the significance of the serum dehydroepiandrosterone sulfate (DHEAS) concentration as a parameter of the individual hormonal milieu, two different groups of subjects were studied: DHEAS levels were determined 3 times at 6-month intervals in 47 elderly hospitalized women, aged 71-94 yr (group 1), and 6 times over 2 consecutive weeks in 10 healthy male volunteers, aged 24-30 yr (group 2). For reference, serum cortisol (F) levels were determined concomitantly. In each group and on each sampling occasion, the subjects were ranked according to their DHEAS or F values. The stability over time of the ranking was much higher for DHEAS than for F; estimated concordance coefficients were 92% (group 1) and 88% (group 2) for DHEAS vs. 51% (group 1) and 49% (group 2) for F. We conclude that due to a comparatively low within- to between-subject variability ratio, DHEAS is a highly specific individual marker.
Adult↗
Application of a new protocol for nested PCR to the detection of minimal residual bcr/abl transcripts.
Nested PCR (NPCR), a two-step procedure in which the products of a first PCR using 'outer' primers are reamplified using 'inner primers', has been successfully used to test for the chronic myeloid leukemia (CML)-specific bcr-abl transcripts. A major drawback of the conventional nesting strategy is linked to the opening of the reaction tube between the two successive PCR reactions, giving a risk of contaminating the second mix with amplicons. In this paper, the application of a new protocol for NPCR without reopening the reaction tube between the two steps of the procedure is described for the research of residual leukemic cells in the peripheral blood of 14 CML patients treated by bone marrow transplantation (BMT) or interferon (IFN). This assay which is both highly specific and sensitive, offers several advantages over the use of conventional NPCR: it is more sensitive, faster and decreases the risk of false-positive results. In addition, chemiluminescent detection of amplified DNA after transfer onto a nylon membrane, although comparable with radioactive hybridization in terms of sensitivity and speed, is more advantageous in safety and convenience. In conclusion, this assay could be adapted to a number of clinical diagnostic uses.
Base Sequence↗
Fast, manual, nonradioactive method for DNA sequencing.
We describe a protocol that allows nonradioactive detection of sequencing products after manual, direct, solid-phase sequencing of polymerase chain reaction-amplified DNA. The amplified DNA fragment to be studied is biotinylated at the 5' end of one of the two oligonucleotide primers used for amplification, allowing coupling to streptavidin-coated magnetic beads. The immobilized double-stranded DNA is then separated into single strands by alkaline treatment. A 5'-biotinylated sequencing primer is used after saturating with a biotin solution any possible remaining affinity sites on the streptavidin-coated magnetic beads. Sequencing is performed by using T7 DNA polymerase, and the sequencing products are electrophoresed in denaturing polyacrylamide sequencing gel. After transfer of the products to a nylon membrane, the sequencing pattern is revealed by chemiluminescence. Biotinylated alkaline phosphatase is bound to the 5' end of the sequencing primer via a streptavidin bridge and catalyzes the reaction by cleaving a phosphate group from a chemiluminescent substrate. The emitted photons are detected by exposing the membrane to x-ray film. This method is simple, rapid, and consistently successful and reproducible.
Base Sequence↗
Antigenic variants of the nonspecific cross-reacting antigen (NCA).
Monoclonal antibodies (Mab) were prepared against nonspecific cross-reacting antigen (NCA) and were selected on the basis of their absence of reactivity with carcinoembryonic antigen (CEA). Four Mab were found which allowed the characterization on CEA of three epitopes, defined A, B, and C. These epitopes were all located on the peptidic moiety of this highly glycosylated antigen and were present on NCA molecules of heterogeneous m.w. (greater than 100,000, 80,000, and 48,000 m.w., the latter being the most abundant). The amount of NCA was estimated in 251 human sera both by a conventional RIA, using a rabbit antiserum, and by EIA, using different Mab: Mab 4, 18, and 33, which reacted, respectively, with epitopes A, B, and C. Each assay gave a different value of the absolute concentration of NCA in the serum. On the whole, Mab 4 gave lower values, whereas Mab 18 and 33 gave higher values as compared to RIA. Furthermore, whereas all of the human sera contained NCA which was measurable by RIA, 67 sera typed negative in EIA when using Mab 4 or 18. Eight additional sera were negative in more than one EIA. Negativity when using Mab 33 was observed in only one serum, which was also negative with Mab 4 and 18. Twenty-five of 30 sera which were negative with Mab 4 came from cancer patients, and 32 of 37 sera negative with Mab 18 came from normal subjects and noncancer patients, giving a statistically highly significant difference between the two groups of sera (p less than 0.001). Analysis of tissue perchloric extracts and NCA samples purified from these extracts gave similar results. Three extracts (one from lung, two from cancer tissue) and the corresponding NCA samples were negative with Mab 18. The discrepancies observed in these assays are best explained by assuming the existence of antigenic variants of NCA which have not been described previously. These variants appear to exist in various proportions in the different sera. The variants may represent antigenically complete and incomplete molecules. Alternatively, most of the NCA molecules may be incomplete, lacking one or another of the several NCA-specific epitopes. Sequential immunoprecipitation experiments were in favor of the second hypothesis, showing that most of the NCA molecules were incomplete, lacking either epitope A or B.
Antibodies, Monoclonal↗
Production of monoclonal antibodies against the non-specific cross-reacting antigen (NCA).
Hybridomas were prepared by fusion of mouse spleen cells immunized with purified NCA (non-specific cross-reacting antigen) with cells of myeloma SP2/0. After cloning, several clones were obtained which produced antibodies specific for NCA, i.e., not reacting with CEA. All antibodies were IgG1 Kappa. Their affinity constants were higher at 4 degrees C than at 37 degrees C. They revealed the existence of at least two epitopes on the specific moiety of NCA.
Animals↗