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Biomedical subjects

F Mitelman

Publications and source records attributed to F Mitelman.

At least 397 records · Page 22Linked to original sources

Variant Ph translocations in chronic myeloid leukemia.

Variant translocations were found in eight of 142 consecutive patients with Ph-positive, chronic myeloid leukemia encountered in our laboratory during the last decade. Two patients had simple, two-way variant translocations: t(17;22)(p13;q11) and t(16;22)(q24;q11). Both of these patients had an additional translocation involving chromosomes #9: t(7;9)(q22;q34) and t(9;17)(q34;q21), respectively. Complex variant translocations were found in four cases: t(2;9;22)(p23q12;q34;q11), t(3;9;22)(p21;q34;q11), t(9;12;22)(q34;q13;q11q13), and t(13;17;22)(p11;p11q21;q11). In two cases, the only discernable cytogenetic aberration was del(22)(q11). A review of the chromosomal breakpoints involved in this series and in 185 cases of variant Ph translocations previously reported in the literature reveals that a disproportionately large number of breakpoints are located in light-staining regions of G-banded chromosomes. Furthermore, the breakpoints in simple variant translocations are more often located in terminal chromosomal regions, whereas, the breakpoints in complex translocations typically affect nonterminal bands. No obvious correlation was detected between variant Ph translocation breakpoints and either fragile sites, oncogene locations, or consistent chromosome breakpoints in other malignancies.

Adult↗

Chromosome analysis in 100 cases of first trimester trophoblast sampling.

The cytogenetic findings in 20 experimental and 80 diagnostic cases of first trimester trophoblast biopsy are presented. All samples were obtained between the 8th and 13th week of gestation with the direct vision, trans-cervical technique. Except when fetal sexing because of X-linked disease was the issue, long-term culture with in situ preparation was the method routinely employed in processing the biopsies for cytogenetic analysis. In 78 of the 80 clinical cases and in all reported experimental cases we were successful in establishing a karyotype from the sampled tissue. Unbalanced karyotypes were found in two experimental and six clinical cases. Tetraploidy was found in one clinical case, but was not confirmed in subsequently sampled amniotic fluid cells. In another clinical case, we were unable to confirm in the aborted placenta the trisomy 18 found in the trophoblast biopsy. In the rest of the induced abortions in the clinical series, the karyotype arrived at prenatally has been confirmed, and the 27 babies so far born have been healthy and with phenotypic sex corresponding to the prenatal findings. Six women have miscarried after sampling; in one of these cases the fetus had the karyotype 47,XX, + 13.

Adult↗

Trophoblast samples suitable for long-term culture.

Chorionic villi were obtained by a direct vision technique. Villi without vessels (38 cases) failed to grow in vitro, irrespective of the amount of tissue. Vascular villi with an estimated weight exceeding 5 mg (71 cases) grew in vitro--with two exceptions.

Biopsy↗

First-trimester diagnosis on chorionic villi obtained by direct vision technique.

An improved technique for direct vision chorionic biopsy that gives a clear view of the amniotic sac was developed. With this technique, used in 48 women prior to vacuum aspiration and in six cases for diagnosis (karyotyping or enzyme analysis), it was possible to obtain chorionic villi free from contamination by maternal tissue. It was also possible to pick out villi (rich in blood vessels and with abundant buds on their surface) found to be most capable of growing in vitro. In the diagnostic cases, the pregnancies have continued uneventfully since the sampling; one pregnancy is now in the 32nd week.

Adult↗

Sister-chromatid exchanges in human lymphocytes after a non-S-phase incubation period to allow excision DNA repair-in vitro exposure to N-acetoxy-2-acetylaminofluorene and ethylene oxide.

Sister-chromatid exchanges (SCE) were analyzed in human peripheral blood lymphocytes at the baseline level, after induction of DNA damage by N-acetoxy-2-acetylaminofluorene (NA-AAF) and ethylene oxide (EO), and after a subsequent 18-h DNA-repair incubation period. There was a significant difference between the baseline SCE frequencies as compared to those after 1 h of NA-AAF or EO treatment. There was no significant difference between the SCE frequencies after 1 h of NA-AAF treatment and those after 18 h of DNA-repair incubation, suggesting that only a low level of NA-AAF damage to DNA had been removed. However, there was a significant difference between the SCE frequencies after 1 h of EO treatment and those after 18 h of DNA-repair incubation, indicating that a significant level of EO induced DNA lesions had been repaired. Thus, it seems likely that the EO induced DNA damage is more easily recognized, and hence more rapidly repaired than the NA-AAF induced damage. The reason for this may be the different chemical nature of the DNA lesions induced, which, in turn, leads to different kinetics of DNA repair.

2-Acetylaminofluorene↗

The relationship between growth in agar, karyotype and prognosis in acute leukaemia.

The growth pattern in agar culture and the karyotype of bone marrow cells were studied in 79 patients with untreated acute non-lymphocytic leukaemia (ANLL). Results were divided into the following groups: (A) colony and cluster formation; (B) growth of less than 600 small clusters per 10(5) cells; (C) growth of more than 600 small clusters; (D) no growth in agar. Cytogenetically, the patients were divided into 3 categories: NN, normal metaphases only; AN, both abnormal and normal metaphases and AA, abnormal metaphases only. An association was seen between growth pattern and karyotype: the majority of NN patients (33/37) belonged to group (A + B) while in group (C + D) 20/24 patients were AN or AA. 37 patients were prognostically evaluable. The growth pattern in agar but not the cytogenetic pattern had prognostic implications. 25 patients with acute lymphocytic leukaemia (ALL) were also studied at diagnosis. Different growth patterns in agar had no impact on prognosis. No relationship was detected between growth pattern and karyotype in ALL.

Acute Disease↗

A twin study of sister chromatid exchanges in human lymphocytes following carcinogen exposure and DNA repair incubation.

Sister chromatid exchanges (SCEs) were analyzed in peripheral lymphocytes obtained from nine healthy monozygotic (MZ) and nine healthy dizygotic (DZ) pairs of male twins. In addition, increases in SCE rates following in vitro treatment of whole blood with 100 microM N-acetoxy-2-acethylaminofluorene (NA-AAF), and after an 18-h DNA repair incubation period, were analyzed in the same twins. There was no significant intrapair difference in the variance of SCE frequencies among MZ and DZ twins at the baseline level, after NA-AAF treatment, or after a DNA repair incubation period. It was concluded that genetic factors probably do not contribute significantly to the individual variation that has been observed in baseline or NA-AAF-induced SCE rates. Thus, any observed alterations in SCE frequencies are probably caused by environmental influences.

2-Acetylaminofluorene↗

A 3q+ marker chromosome in EBV-carrying nasopharyngeal carcinomas.

The malignant epithelial cells of two anaplastic EBV-carrying nasopharyngeal carcinomas (NPC) were investigated cytogenetically by Giemsa banding technique. Both tumors had a similar 3q+ marker chromosome with an involvement of band q25, either a duplication of the region q25-q27, or insertion of an unidentified segment at band q25.

Animals↗