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Biomedical subjects

A Amiel

Publications and source records attributed to A Amiel.

At least 73 records · Page 4Linked to original sources
PubMed1995

Eilatin: a novel marine alkaloid inhibits in vitro proliferation of progenitor cells in chronic myeloid leukemia patients.

We examined the effect of Eilatin, a novel marine product, on the survival of human myeloid progenitor cells (CFU-C) isolated from normal individuals and from 12 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared its effect to the effect of interferon-alpha (IFN-alpha) and cytosine arabinoside (Ara-C). Eilatin, IFN-alpha, and Ara-C inhibited the proliferation of CFU-C from normal individuals and CML patients in a dose-dependent manner. The percent survival of colony-forming units from bone marrow (BM) of seven CML patients in chronic phase exposed for 16 hours to Eilatin (10(-7) and 10(-6) M), IFN-alpha (500 U/mL), or Ara-C (10(-9) M and 10(-8) M) was found to be statistically lower (p < 0.05) than the percent survival of myeloid progenitors from normal individuals. A 16-hour exposure of CD34+ cells isolated from peripheral blood (PB) of three CML patients in blastic crisis and from BM of two patients in chronic phase to Eilatin 10(-7) M, IFN-alpha 500 U/mL, Ara-C 10(-9) M resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using fluorescent in situ hybridization (FISH), we evaluated detection of the BCR/ABL fusion product in the CD34+ cells. All five patients were 100% Ph+ at diagnosis. BCR/ABL translocations were detected in 94.6 +/- 0.6% of CD34+ cells after growth in liquid culture for 7 days. The level of BCR/ABL fusion signals detected after exposure of CD34+ cells for 16 hours to Eilatin 10(-7) M, IFN-alpha 500 U/mL, or Ara-C 10(-9) M were 54.5 +/- 5%, 63.6 +/- 5%, and 70 +/- 4%, respectively (mean +/- SE, n = 5). Our data indicate that Eilatin, a substance isolated from the Red Sea purple tunicate Eudistoma sp., has an antileukemic effect against in vitro Ph+ cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or PB of CML patients in conjunction with autologous bone marrow transplantation.

Adolescent↗
PubMed1995

[Coronary artery disease in hypertensive patients: improvement of the diagnostic value of exercise test by heart rate adjusted ST segment depression].

UNLABELLED: Hypertensive patients complaining of chest pain often have a normal coronary angiogram despite a pathological exercise tolerance test. The aim of the present study was to establish whether the prevalence of these "false-positive" tests could be lowered by adjusting ST segment depression for exercise-induced increase in heart rate. METHODS: 60 hypertensive patients, mean age 59 years, with typical or atypical chest pain, underwent both a symptom-limited exercise test and a coronary angiogram within a median period of 1 day. The ST segment depression was measured every 20 ms from the J point. A stepwise discriminant analysis was performed: a canonical variable took into account the Detrano index, the quantified rate-recovery loop index (QRL index) as well as the presence of a LV hypertrophy (Romhilt Estes Score). RESULTS: [table: see text] CONCLUSION: in hypertensive patients with chest pain, the specificity and the positive predictive value of exercise test are significantly improved by adjusting ST segment depression for heart rate both during effort and recovery and by taking into account the score of Romhilt Estes on the baseline ECG recording.

Aged↗
PubMed1995

Potent antileukemic activity of the novel agents norsegoline and dibezine.

We examined the effect of norsegoline, a natural marine product, and dibezine, a synthetic product, on the survival of human myeloid progenitor cells [colony-forming unit-cells (CFU-C)] from normal individuals and from 10 patients with Philadelphia-positive chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared their effect to the effect of IFN-alpha. Norsegoline, dibezine, and IFN-alpha inhibited the proliferation of CFU-C in a dose-dependent manner. The number of CFU-C from bone marrow (BM) of five CML patients in chronic phase exposed for 16 h to norsegoline (10(-8)-10(-6)M), dibezine (10(-8)-10(-6)M), and IFN-alpha (500 units/ml) was found to be statistically lower (P < 0.05) than the number of CFU-C derived from normal individuals. A 16-h drug exposure of CD34(+) cells isolated from the peripheral blood of three CML patients in blastic crisis and from BM of two patients in chronic phase resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using the fluorescent in situ hybridization technique, we evaluated detection of the BCR/ABL fusion product in the CD34(+) cells. All five patients were 100% Philadelphia positive at diagnosis. BCR/ABL translocations were detected in 94.6 +/- 0.6% of cells following their growth in liquid culture for 7 days. Following exposure of CD34(+) cells to norsegoline, dibezine, or IFN-alpha, BCR/ABL fusion signals could be detected in 73 +/- 11%, 66.5 +/- 4. 7%, and 66.0 +/- 2.5% of cells from BM and 72.3 +/- 5%, 68.8 +/- 7%, and 60.6 +/- 6.8% of peripheral blood, respectively. Our data indicate that norsegoline and dibezine have in vitro an antileukemic effect against Philadelphia-positive cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or peripheral blood of CML patients in conjunction with autologous bone marrow transplantation.

Adolescent↗
PubMed1994

Delta-T-lymphocytosis in a patient with thymoma.

BACKGROUND: Malignant thymoma is composed of neoplastic epithelial cells and small lymphocytes. Rarely, patients also may have peripheral T-lymphocytosis. These lymphocytes have been considered nonneoplastic because of their microscopic appearance and immunophenotype, as well as gene rearrangement studies. METHODS: A 42-year-old man developed lymphocytosis 3 years after the completion of intensive combined chemoradiotherapy protocol for lymphocytic thymoma. These peripheral blood lymphocytes were evaluated phenotypically and genotypically. RESULTS: Immunophenotyping established that the cells were CD3 positive, CD4 negative, CD8 negative, T-cell receptor (TCR)-alpha/beta negative, and TCR-gamma/delta positive. Gene rearrangement studies with TCR-delta probe confirmed the monoclonality of these cells. Chromosome analysis showed deletion of chromosome Y. The clinical course was progressive and had the features of malignant lymphoma. CONCLUSIONS: To the authors' knowledge, this is the first report of a patient with thymoma in whom monoclonal proliferation of T-gamma/delta peripheral blood lymphocytes was confirmed immunophenotypically and genotypically. These monoclonal TCR-gamma/delta lymphocytes may belong to the malignant clone of the thymoma; however, the possibility that they represent an evolution of a second lymphatic malignancy cannot be excluded.

Adult↗
PubMed1994

Systemic chimerism in sex-mismatched liver transplant recipients detected by fluorescence in situ hybridization.

Fluorescent in situ hybridization (FISH) is a reliable, rapid, sensitive, and quantitative method for detection of residual host cells following sex-mismatched bone marrow transplantation. Recently, donor-derived long-term multilineage hematopoiesis was detected in a sex-mismatched liver transplant recipient. We therefore assessed chimeric status in 12 patients (F 9, M3), mean age 42.5 years (range 16-57), for a median period of 18 months (range 7-32) following sex-mismatched liver transplantation. Peripheral blood hematolymphoid cells were hybridized with Y- or X-chromosome fluorescently labeled specific probes, and the donor-typed hematopoietic cells were enumerated. In two F recipients 4-5% male hematolymphoid cells were detected in the peripheral blood at 15 and 22 months after sex-mismatched liver transplantation, respectively. These two patients with systemic chimerism suffered from primary biliary cirrhosis and fulminant Wilson's disease before transplantation. One of them had evidence of graft rejection only once during the posttransplant course and the other had no episode of graft rejection. Two other female patients who were found to have approximately 2% male hematolymphoid cells, which is considered to be in the false-positive range, also had no signs of graft rejection during the posttransplant follow-up period. Among the remaining eight patients, in whom systemic chimerism was undetectable, there was at least one episode of acute cellular rejection during the posttransplant period. In summary, the FISH technique enables us to detect systemic chimerism following sex-mismatched liver allografts. Inasmuch as balanced systemic chimerism after organ transplantation is of major importance for self tolerance, our findings may enable us to treat patients after liver transplantation without the need for immunosuppression.

Adult↗
PubMed1994

Detection of minimal residual disease state in chronic myelogenous leukemia patients using fluorescence in situ hybridization.

Detection of minimal residual disease and relapse remain major problems in chronic myelogenous leukemia (CML) patients following bone marrow transplantation (BMT). In order to disclose the 9;22 Philadelphia translocation, we used a fluorescence in situ hybridization (FISH) technique. BCR and ABL gene fragments were used as probes for the detection of the BCR/ABL fusion product in peripheral blood and bone marrow cells from 11 CML patients in which 5 were post-BMT. The sensitivity and specificity of this approach were compared to conventional cytogenetic and polymerase chain reaction (PCR) methods. FISH demonstrated a high degree of sensitivity (1%) for the detection of the BCR/ABL translocation in these patients. A linear correlation was found between FISH detection of the BCR/ABL fusion product and routine chromosomal analysis (r = 0.995; p < 0.001). Detection of the BCR/ABL signal by FISH was observed in all patients showing a positive PCR signal. A significant reduction in BCR/ABL signal was observed post-transplant (p < 0.001). However, the BCR/ABL translocation was detected in four of five transplanted patients immediately (0.75-2.5 months) following transplant and was found in patients with a low expression of the translocation.

Adult↗
PubMed1994

Detection of minimal residual disease after sex-mismatch bone marrow transplantation in chronic myelogenous leukemia by fluorescence in situ hybridization.

Detection of minimal residual disease is one of the major goals in bone marrow transplantation. We used a fluorescence in-situ hybridization technique to detect residual Philadelphia-chromosome positive cells in chronic myelogenous leukemia (CML) patients after sex-mismatch BMT. We analyzed the level of detection using probes for the BCR/ABL fusion product by comparison with results obtained with probes for the Y and X sex chromosomes. Detection of sex-mismatch chromosomes was significantly higher than that of the BCR/ABL translocation. In contrast, a higher specificity of residual tumor cell detection by the BCR/ABL probe was demonstrated because most of the sex-mismatch cells detected by FISH had a normal karyotype. Tumor-specific markers probes are thus superior and more accurate than sex-mismatch probes for detection of MRD in CML patients after BMT.

Adult↗
PubMed1994

Detection of bcl rearrangements in B-CLL by fluorescence in situ hybridization.

Data concerning oncogene activation in CLL are very limited. When studied by Southern blot, rearrangements of bcl-1, bcl-2, and bcl-3 have been only infrequently reported. We evaluated the role of fluorescence in situ hybridization (FISH) in the detection of gene rearrangements in two CLL patients. We used multiple DNA probes, including those of chromosome 12, immunoglobulin heavy and light chains, and the oncogenes bcl-1, bcl-2, and bcl-3. Additionally, routine cytogenetic study was performed. In one patient, trisomy 12 and bcl-2 translocation were demonstrated by both methods, while trisomy 12 and bcl-1 translocation were seen in the second patient, who had a normal karyotype. Larger studies should evaluate the role of FISH in the detection of oncogene involvement in CLL and compare it with other molecular methods.

Aged↗
PubMed1994

Prenatal testing for Down syndrome in the Jewish and non-Jewish populations in Israel.

The present work evaluated the efficacy of a prenatal diagnosis program in which amniocentesis and chorionic villus sampling were offered free of charge to all pregnant women in Israel aged > or = 37 years. The number of Down syndrome (DS) live births that occurred during the period of the program (1978-92) was correlated to the prevalence of old maternal age (> 35 years) and the utilization of prenatal test in the Jewish and non-Jewish populations in 1990 and 1992. It was noted that in the Jewish population, there was a slight increase in the DS live birth rate, from 1.05 in 1978, to 1.37 DS cases/1,000 live births in 1987, which corresponded to an increase in the prevalence of older pregnant women, from 8.0% in 1978 to 14.8% in 1987. Thereafter, however, there was a continuous decline, to 0.71 DS cases/1,000 live births in 1992, as a result of increased acceptance of prenatal testing by women > or = 37 years (67%) and, recently, also by younger women (from 5.6% in 1990 to 14% in 1992). In the non-Jewish population, there has been a very low acceptance rate of prenatal testing (23.3-16.1% in women > or = 37 years and 0.36-0.63% in women < 37 years). As a result, a very low prenatal detection rate (8-16% of all DS cases) and a high prevalence of DS live births (1.4 cases/1,000 live births) were observed. We suggest that a unique genetic counseling approach is required in the non-Jewish population to improve prenatal DS prevention in Israel.

Adult↗
PubMed1993

In situ hybridization: a simple and sensitive method for detection of trisomy 12 in chronic lymphocytic leukemia.

Chromosome aberrations are detected in only 50% of patients with chronic lymphocytic leukemia (CLL), owing usually to the low mitotic rate exhibited by the neoplastic lymphocytes. Fluorescence in situ hybridization (FISH) is a simple method for identifying numerical abnormalities of the target chromosome in interphase nuclei. Therefore, we used the FISH procedure with chromosome 12-specific a-satellite probe to evaluate 19 patients with CLL. Trisomy 12 was detected in interphase cells of 12 patients (63%). Cytogenetic analysis, performed in nine patients, yielded trisomy 12 in four (44%). FISH detected three patients with trisomy 12 in whom conventional cytogenetic method yielded a normal karyotype. FISH is a simple, reliable, and sensitive method for detection of trisomy 12 in patients with CLL.

Aged↗
PubMed1993

Elevated human chorionic gonadotropin levels in pregnancies with sex chromosome abnormalities.

Numerous reports have dealt with the usefulness of the maternal serum alpha-fetoprotein marker (MsAFP) and human chorionic gonadotropin (MshCG) levels in the detection of Down syndrome (DS) and other autosomal trisomies. Only few reports have discussed the possible association of elevated levels of MshCG and sex chromosome aneuploidy. We wish to report on 3 cases in which this association was found.

Adult↗
PubMed1993

The correlation between the frequency of sister-chromatid exchange and human reproductive hormones.

Different frequencies of sister-chromatid exchanges (SCEs) during various stages of the menstrual cycle have previously been observed. We tested the hypothesis that sex hormones, particularly steroids, influence the frequency of SCEs in women undergoing ovulation induction for in vitro fertilization treatment. These women undergo extreme hormonal changes and therefore serve as a good model for testing the rate of genetic damage due to these changes. As controls, we tested fertile women with regular menstrual cycles who received no hormonal treatment. Peripheral lymphocytes were obtained during different stages of the normal and treated cycles. We examined SCE frequency as related to the different hormones of the reproductive cycle at each of the stages. In general, an increased SCE frequency was observed around ovulation time in the controls, and around the time of human chorionic gonadotropin administration in the group undergoing ovulation induction. However, in the latter group, SCE frequency was significantly higher. SCE frequency was positively correlated with the level of testosterone and FSH in the ovulation induction group, and positively correlated with the estradiol level in both groups.

Adult↗
PubMed1993

Clinical detection of BCR-abl fusion by in situ hybridization in chronic myelogenous leukemia.

We describe the use of the fluorescence in situ hybridization (FISH) technique to detect residual Philadelphia chromosome-positive (Ph+) cells in a patient with blastic phase chronic myelogenous leukemia (CML) after aggressive cytoreductive treatment. The analysis was made in interphase nuclei because of the very small number of recognizable metaphases in leukemic patients. FISH was a reliable tool for the detection of chromosome translocations in interphase nuclei as compared with conventional cytogenetic and polymerase chain reaction (PCR) techniques.

Adult↗
PubMed1993

Fluorescent in situ hybridization for the detection of t(8:14) in Burkitt's lymphoma.

Burkitt's lymphoma cells exhibit the reciprocal balanced chromosomal translocation t(8:14) in 75% of patients. Cytogenetic analysis is time-consuming, requires in vitro culture with mitogens and enables to analyse a relatively small number of cells. We evaluated the role of multicolor fluorescent in situ hybridization (FISH) in the rapid detection of t(8:14) in Burkitt's lymphoma cells. FISH detected the JH/myc translocation in 100% of the cells of five cell lines carrying the classical t(8:14) and in fresh cells obtained from a newly diagnosed Burkitt's lymphoma patient. In contrast, the translocation was not detected in the Bajb cell line that does not carry t(8:14). We conclude that FISH is a rapid and reliable diagnostic tool for the detection of the JH/myc translocation in Burkitt's lymphoma patients.

Biopsy, Needle↗
PubMed1992

The dilemma of a low rate of chromosomal mosaicism found in fetal blood sampling.

We report a case in which mosaicism of trisomy 13 was detected in 4/10 cells (40 per cent) in amniotic fluid cell cultures, followed by a low rate of mosaicism (1/160 cells) detected in a fetal blood sample. This finding presents a dilemma both for the genetic counsellor and for the parents in determining whether or not to terminate the pregnancy.

Adult↗