Chromosome breakage in control and fragile X subjects using folate-deficient culture conditions.
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Adolescent↗
Biomedical subjects
G M Joseph
Publications and source records attributed to G M Joseph.
Metaphase chromosome folds and X-inactivation.
To evaluate the suggested nonrandom folding of Xq13-q21 (center of Barr body condensation) of the inactivated X chromosomes, metaphases from nine subjects with or without X chromosome abnormalities (eight females and one male) were investigated with RBG-staining. A significant increase (p less than .05) in the number of arm folds (Xq13-q21) of the late-replicating X chromosome, particularly in early to mid-metaphase, was observed in four of eight females. Therefore, the stage of chromosome contraction was an important factor with more folds observed at the centromeres and in longer chromosomes in early metaphase compared with mid- to late metaphase. X chromosome folds were present in cells of subjects treated with or without bromodeoxyuridine. While our study agrees with the relationship of Xq13-q21 fold with the X-inactivation center, the correlation of extended chromosomes and folding limits this method as a sole indicator of X-inactivation in routine mid-metaphase, but is useful in the analysis of early metaphase chromosomes.
Dosage Compensation, Genetic↗
High resolution chromosome and DNA analysis in multiple endocrine neoplasia type II syndrome.
Multiple endocrine neoplasia type II (MEN-II or Sipple's syndrome) is an autosomal dominant disorder characterized by medullary thyroid cancers, pheochromocytomas, and parathyroid adenomas. A blind analysis of high resolution G-banded chromosomes was performed on blood specimens from eight MEN-II individuals from three unrelated families and six control subjects. Seven of eight MEN-II patients and one of six control subjects were determined to have a deletion at 20p12.2. These findings support the hypothesis that MEN-II patients have a 20p12.2 deletion (chi 2 = 6.99; p less than 0.01). Genomic DNA from seven of the eight MEN-II patients was studied using the DNA probe, D20S5, localized by in situ hybridization to 20p12. The probe binding site is not deleted in some MEN-II patients, as demonstrated by the presence of two alleles detected as restriction fragment length polymorphisms. Thus, D20S5 does not hybridize to DNA sequences that are deleted based on cytogenetic analysis in MEN-II patients.
Alleles↗
Cytogenetic studies of individuals from four kindreds with multiple endocrine neoplasia type II syndrome.
Multiple endocrine neoplasia type II (MEN-II) syndrome is an autosomal dominant condition characterized by medullary carcinoma of the thyroid, pheochromocytoma, and parathyroid adenoma. A cytogenetic investigation was conducted on 13 MEN-II syndrome patients from four unrelated kindreds and 13 age-matched control subjects for chromosome instability and the chromosome 20 deletion reported in MEN-II syndrome. A significant increase (p less than 0.05) was found in the total number of chromatid and chromosome aberrations in MEN-II cells (12.3%) compared with control cells (6.9%) grown at 96 hours in mitomycin C (20 ng/ml, final concentration). The major difference between the two groups was in chromatid, and not chromosome, aberrations. There was no difference between MEN-II and control individuals in fragile site expression, the number of sister chromatid exchanges or cell kinetics. A blind analysis of high-resolution G-banded chromosomes was performed on blood specimens from 13 MEN-II and seven control individuals. Twelve of 13 MEN-II patients and one of seven control subjects were scored as having a 20p12.2 deletion (chi 2 = 12.6; p less than 0.001). Additional research is needed to determine if this cytogenetic finding is due to a chromosome deletion, inversion, or polymorphism.
Adult↗
Domain knowledge and hypothesis generation in diagnostic reasoning.
The role of domain knowledge in the process of hypothesis generation during diagnostic reasoning was examined. Subjects were given a clinical case presented one segment at a time on a microcomputer. They were prompted to think aloud after presentation of each segment of the clinical case. A combination of discourse and protocol analysis techniques was used to investigate the problem solving process in two groups of experts working on an endocrine problem. The groups consisted of high-domain-knowledge subjects (HDK), endocrinologists, and low-domain-knowledge subjects (LDK), cardiologists. The results showed no significant differences between the groups in terms of selection of relevant and critical cues from the case. However, specific differences were found in the links or relations between the cues, with the HDK subjects using more relations to connect important information. The HDK subjects generated accurate diagnostic hypotheses early in the problem encounter and spent the rest of the time confirming the hypotheses by explaining the given cues. The LDK subjects also generated accurate diagnostic hypotheses but were unable to discriminate between and eliminate alternative hypotheses. A two-stage problem solving process and its relationship to domain specific knowledge are proposed.
Clinical Competence↗