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Interphase cytogenetic analysis of cervical intraepithelial neoplasia.

The aim of this study was to detect numerical chromosomal aberrations that may be involved in the progression of cervical intraepithelial neoplasia (CIN) toward cervical carcinoma. Therefore, cervical lesions (five CIN 1, seven CIN 2, six CIN 3, six invasive carcinomas, and six normal samples) were studied by in situ hybridization (ISH) on serial 3-microm-thick paraffin tissue sections, using a panel of eight centromeric DNA probes for chromosomes 1, 3, 6, 7, 8, 11, 17, and X. An estimation of the percentage of dysplastic epithelium with abnormal ISH signals per nucleus was made. Chromosome aneusomy could be detected in all persisting and high-grade CIN lesions and invasive carcinomas. In most cases, when one of the chromosomes showed aneusomy then all studied chromosomes showed numerical changes. Interestingly, the abnormal ISH signals were found only in a varying part of the morphologically dysplastic epithelium, the remainder showing no such changes. In aneuploid regions of the CIN 1 lesions the mean chromosome index for all chromosomes was 1.97+/-0.03 with a range of 1.92 to 2.00. The chromosome index ratios of chromosomes 1, 7, and X showed a significant positive correlation with CIN grade (r > or = 0.74; P < or = 0.006). It is concluded that chromosome aneusomy of chromosomes 1, 7, and X may be involved in the progression of CIN lesions.

Adult↗

The cellular interphase.

A brief outline is given of the impact of molecular genetics on the study of morphogenesis. Two approaches have been used, one beginning at the molecular level and applying knowledge gained in this way to observations of whole organisms; the other starting with descriptions of the organism and tracing the causes of developmental changes to cellular and then molecular events. The availability of experimentally induced mutants has facilitated the study of development, but such work must be combined with detailed information on the normal process. Comparative studies have exploited evolutionary conservation to identify functionally important gene activities, and allowed knowledge gained from one organism to be rapidly applied to other species. The successes achieved at the molecular level are impressive, but the time has come to return to studying the cells that are the real mediators of the transmission of the genetic information.

Animals↗

A computer simulation of conduction block: effects produced by actual block versus interphase cancellation.

A reduction in compound muscle action potential (CMAP) amplitude and area following proximal versus distal stimulation is the accepted clinical hallmark of conduction block; however, quantitative criteria for determining conduction block remain ambiguous. In this study, digitized records of individual motor unit action potentials (MUAPs) elicited by incremental stimulation in vivo were arithmetically combined in a computer simulation of CMAP generation. Through simulation of possible phase interaction patterns of individual MUAPs, we have shown that abnormal temporal dispersion alone can produce reductions in CMAP area of up to 50%, values that are commonly thought to represent conduction block. Furthermore, by simulating conduction block without excessive temporal dispersion in defined subpopulations of axons, we have demonstrated the importance of the fastest conducting (largest MUAP) axons in determining CMAP amplitude and area. In conclusion, measurements of CMAP amplitude and area in determining conduction block may be misleading if there is significant abnormal temporal dispersion, and quantitation of the degree of conduction block is difficult without knowledge of which subpopulations of axons are affected.

Action Potentials↗

Detection of numerical and structural chromosome abnormalities in pediatric germ cell tumors by means of interphase cytogenetics.

In contrast to the cytogenetically well characterized testicular germ cell tumors (GCT) in adults, reports on cytogenetic studies in pediatric GCT are scarce. The presence of an i(12p) and numerical abnormalities involving chromosome 12 are the most frequent cytogenetic changes in GCT of adults. We have performed in situ hybridization (ISH) studies on paraffin sections and on isolated nuclei of 13 pediatric GCT with particular emphasis on those chromosome abnormalities that are common in adult GCT. These include numerical and structural abnormalities of chromosomes 1 and 12 as well as numerical deviations of chromosomes 8, 10, X, and Y. The histological subsets of the tumors investigated included two dysgerminomas (DGE), one seminoma (SE), two embryonal carcinomas (EC), four mixed and two pure yolk sac tumors (YST), and one undifferentiated (IT) and one differentiated teratoma (TD). Similar to the GCT in adults, additional copies of chromosome 12 were the most frequently observed numerical abnormalities. In contrast to the findings in adult GCT, changes in the size of the pericentromeric hybridization signals of chromosome 12, suggesting the presence of i(12p) chromosomes, were found in only two cases. No chromosome abnormalities were found in the pure TD or in the TD cells of mixed tumors containing a YST component. In the YST portion, however, Ip deletions and/or numerical chromosome changes were present. Surprisingly, deletions of the short arm of chromosome I, del(I)(p36.3), were frequent in pediatric GCT and were the sole abnormality detected in two cases. The Ip36 deletions were present in all stage-IV EC and YST investigated and were absent in the relatively benign TD and in one YST stage-I. Therefore, Ip36 deletions may have value as a prognostic marker in pediatric GCT.

Adolescent↗

Chromosome aberrations in adenomas of the colon. Proof of trisomy 7 in tumor cells by combined interphase cytogenetics and immunocytochemistry.

Thirty-five colon adenomas from 26 patients were analyzed with centromeric probes for chromosomes 1, 7, 17, X and Y in order to study numerical aberrations, chromosome imbalances, aneuploidy and tetraploidization. The fluorescent in situ hybridization (FISH) technique was applied to single-cell suspensions and a combination of FISH and immunocytochemistry (ICC) was employed to identify the cell type under study. Trisomy of chromosome 7 was detected in 37% of the cases. In 7 out of 13 cases this aberration was combined with abnormalities of one or 2 of the other investigated chromosomes. No correlation could be demonstrated between any of the detected chromosomal aberrations and size, localization or degree of epithelial dysplasia. With the combined FISH/ICC procedure, the abnormal cells were shown to be of epithelial rather than of stromal origin. Our data indicate that trisomy 7 is a common chromosome aberration in the epithelial component of colon adenomas.

Adenoma↗