The genes for acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) are located within regions subject to non-random chromosomal abnormalities in the myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). Acetylcholinesterase is mapped to 7q22, within the critical deleted region presumed to contain a myeloid specific tumour suppressor gene. Butyrylcholinesterase is mapped to 3q26: abnormalities at this region are associated with sub-types of MDS and AML with thrombocytopenia, or with increased platelet counts. Both ACHE and BCHE have been implicated as playing a role in megakaryopoiesis and thrombopoiesis, and these genes have been observed to be co-amplified in acute myeloid leukaemia. Recent findings suggest a more significant role for the ACHE gene in haemopoiesis by regulating multipotent stem cell proliferation, and apoptosis in cells undergoing erythroid and myeloid differentiation. This led us to investigate gene copy-number alterations at these genes in MDS and AML. Samples were screened by slot-blot hybridization, and if changes were observed, by Southern blotting. A total of 42 samples from 31 de novo AML patients, 10 samples from eight cases of post-MDS AML and 85 samples from 67 MDS patients were analysed with probes for ACHE, BCHE, c-MYC, MDR-1 and globin control. Changes in ACHE and/or BCHE were observed in 9/31 de novo AML patients, and in 7/67 MDS patients: 1/37 cases of refractory anaemia (RA), 1/10 cases of refractory anaemia with excess blasts (RAEB) and 5/20 chronic myelomonocytic leukaemia (CMML) patients. The amplification events observed generated copy numbers no greater than 10, showed normal restriction patterns and had no clear correlation with megakaryopoiesis or thrombopoiesis. Loss of signal at the ACHE locus was observed: haploid signal intensity was seen in seven samples: one RA with thrombocytopenia, three CMML, one AML-M5a (no karyotypic abnormalities of chromosome 7), one AML-M4 (monosomy 7), and one case of AML-M7 (karyotype unknown). Homozygous deletion was observed at relapse of an additional patient with AML-M4. These data reinforce the possibility that ACHE may play a role as a myeloid tumour suppressor gene.

Acetylcholinesterase↗

PubMed1996

Situational familiarity and feature recognition in schizophrenia.

Research has shown that schizophrenia patients are less able to identify a situation's abstract features (goals) than its concrete features (actions). However, it has been unclear whether this differential deficit represents a cognitive dysfunction or a lack of familiarity with many situations because of impoverished social experiences. Twenty-nine inpatients with DSM-III-R diagnosis of schizophrenia completed the Situational Feature Recognition Test, Version 2 (SFRT-2). The SFRT-2 included familiar and unfamiliar situations of which subjects were asked to identify characteristic goals and actions. A 2 x 2 x 2 analysis of variance (group by feature abstraction by situational familiarity) found a significant three-way interaction. Post-hoc analyses suggested that patients were better able to recognize concrete features in familiar situations. Differences in discriminating power of the four conditions of the SFRT-2 had been diminished on standardization and cross-validation groups. Therefore, the differential deficits shown by the patient sample probably do not represent psychometric confound. Implications for remediation of social cognitive deficits are discussed.

Adult↗

PubMed1996

Sensitive and reliable PCR and sequencing used to detect p53 point mutations in fine needle aspirates of the breast.

AIMS/BACKGROUND: Fine needle aspirates (FNAs) of breast lesions are now a routine investigation and prognostic information at this stage would be useful for accurate management, p53 gene status can be used as prognostic indicator, an abnormal genotype being associated with high grade, oestrogen receptor poor tumours. As the main disadvantage with FNA is poor cellularity, the objective of this study was to develop a sensitive and reliable method for the assessment of the p53 status of the lesion. METHODS: Using PCR and subsequent direct sequencing, a method was developed that enables analysis of the p53 gene from relatively few malignant or suspicious cells in a background of normal cells. RESULTS: This method is both reproducible and sensitive. The sensitivity of the method is demonstrated and a mutant cell can be seen in a background of 90% of normal wild type cells. A mutation, not previously described in breast cancer, is also reported in a symptomatic FNA. CONCLUSIONS: This methodology is reliable and effective on samples with both variable cell numbers and quality of preservation, allowing it to be applied successfully to diagnostic cytology.

Base Sequence↗