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At least 19 recordsLinked to original sources
PubMed1992

Chromosome fragility and psychopathology in obligate female carriers of the fragile X chromosome.

The relationship between fragility (the percentage of cells exhibiting the fragile X chromosome abnormality) and psychopathological conditions was investigated in a sample of 40 obligate female carriers of the fragile X chromosome. Subjects were categorized by those with positive fragility greater than 0% (n = 19) and those with 0% fragility (n = 21). Compared with women with 0% fragility, it was expected that women with positive fragility would have a higher likelihood of manifesting a spectrum of social and psychological disability previously shown to be associated with fragile X syndrome in women. It was also expected that within the group with positive fragility, degree of fragility would be related to severity of symptoms. Results partially supported the hypotheses: women with fragility over 0% were more likely to be assigned a diagnosis of schizotypal features, were rated higher on symptoms associated with the schizophrenia spectrum, and scored lower on IQ, level of healthiest functioning, education, and socioeconomic status than women with 0% fragility. Subsequent comparisons with a control group indicated that the group with 0% fragility and normal controls did not differ on these variables. Within the group with positive fragility, increasing fragility was related to greater severity of symptoms and lower IQ, education, socioeconomic status, and levels of adaptive functioning, as predicted. Contrary to expectations, positive fragility was not associated with proportion of affective disorder diagnoses or ratings on affective disorder symptoms. The results of the study provide evidence that degree of fragility is a potentially important predictor of psychopathology among women with normal IQ who are carriers of the fragile X chromosome abnormality.

Adult↗
PubMed1992

Chromosome fragility in the Lennox-Gastaut epilepsy syndrome.

Chromosome fragility was sought in a well-defined cohort of patients with Lennox-Gastaut epilepsy syndrome. Twenty-five patients plus 25 age- and sex-matched normal controls had cytogenetic studies performed. All patients were taking sodium valproate, and four were also on hydantoin. Blood cultures from both patients and controls were set up simultaneously in an appropriate medium designed to elicit fragile-sites. Harvesting took place after 96 h by standard techniques. In addition to routine banded analysis, at least 50 cells were scored for chromosome breaks and gaps from each patient and control. Results showed no difference between the patients and the control group in the overall occurrence of fragility or the type of aberration detected. No fragile-X syndrome was detected. This study found no effect due to sodium valproate on the occurrence of chromosome aberrations.

Adolescent↗
PubMed1991

Chromosomal fragile site expression in dogs: I. Breed specific differences.

Peripheral blood lymphocytes from clinically normal Doberman pinscher and boxer dogs were cultured for folate-sensitive and, in preliminary studies, aphidicolin-inducible fragile site expression. Both autosomal and X chromosomal fragile sites were observed in canine cells cultured under folate/thymidine depletion and in cells cultured in medium containing aphidicolin. Results from the three dogs evaluated for both folate-sensitive and aphidicolin-inducible fragile site expression showed that the frequency of fragile site expression was significantly (P less than 0.05) greater in cells cultured in medium containing aphidicolin than in cells cultured in folate/thymidine-depleted medium. Cells from the boxer dog expressed a high percentage (66.67%) of aphidicolin-inducible fragile sites in contrast to the Doberman pinscher dog in which only 21.10% of the lymphocytes expressed aphidicolin-inducible fragile sites. The frequencies of spontaneous and folate-sensitive fragile site expression did not vary significantly by breed of dog. Age of dog was significantly and positively correlated with frequency of folate-sensitive fragile site expression in dogs of the boxer breed, but not in dogs of the Doberman pinscher breed. The dog X chromosome expressed three folate-sensitive and aphidicolin-inducible fragile sites. The G-band location of these three fragile sites showed homology with three recognized constitutive common fragile sites on the human X chromosome: Xp22, Xq21, and Xq27.2. Two specific autosomal fragile sites were identified, one on the distal end of the long arm of chromosome 1 and one on the distal end of the long arm of chromosome 8. Other autosomal fragile sites were also apparent but could not be assigned reliably to specific chromosomes.

Aging↗
PubMed1990

No difference in expression of chromosomal fragile sites in patients with solid malignant tumours and normal controls.

The frequency and distribution of rare and common chromosomal fragile sites in metaphases derived from peripheral lymphocytes were compared in 26 patients with malignant solid tumours and 24 normal controls. In order to avoid bias in evaluation, the identity of each individual as patient or control was disclosed only after the study was completed. Rare heritable folic acid inducible fragile sites were found in five patients (2q13; 6p23; 8q22; 16p12) and two controls (8q22). Common fragile sites were present in 21 of 26 patients and in 19 of 24 controls. These differences are statistically not significant in the Fisher test. We conclude that the expression of fragile sites does not indicate a predisposition for solid tumours.

Chromosome Fragile Sites↗
PubMed1990

Prevalence of primary cutis verticis gyrata in a psychiatric population: association with chromosomal fragile sites.

The prevalence of cutis verticis gyrata was studied in a psychiatric institutional population of 494 patients, the majority of whom were mentally retarded or had chronic schizophrenia. Twenty-two subjects (21 males and 1 female) were found to have primary cutis verticis gyrata, yielding a prevalence of about 4.5%. The frequency of the scalp disorder was 11.4% among mentally retarded patients and 1.7% in schizophrenic subjects. A cytogenetic study was performed on patients with primary cutis verticis gyrata. In 9 out of 21 subjects there was evidence of chromosomal fragile sites: 5 patients had fragile sites on the X-chromosome, in 2 there was fragility of chromosome 12 and in 2, fragility of chromosome 9. The fragile X-site is the genetic marker of the 'fragile X-syndrome', a sex-linked inherited disorder often associated with mental retardation and other neuropathological findings.

Adult↗
PubMed1991

Chromosomal fragile site expression in dogs: II. Expression in boxer dogs with mast cell tumors.

Peripheral blood lymphocytes from boxer dogs with a history of cutaneous mast cell tumors were cultured for fragile site expression. As in a control group of dogs, cells from these dogs expressed folate-sensitive autosomal and X chromosome fragile sites. Cells from boxer dogs with mast cell tumors expressed the same three common fragile sites on the X chromosome as cells from control dogs. Three folate-sensitive autosomal fragile sites not observed in cells from the control dogs were identified in cells from boxers with mast cell tumors. These included fragile sites near the telomeres of the arms of chromosomes 3 and 4 and a fragile site on the distal half of chromosome 15. Cells from boxers with mast cell tumors showed a greater frequency of fragile site expression than did cells from control dogs, but this observation was attributed to an unintended selection bias for younger boxer dogs without mast cell tumors and older boxer dogs with mast cell tumors and an increased frequency of fragile site expression with increasing age in dogs of the boxer breed.

Aging↗
PubMed1992

Chromosome fragility in lymphocytes of women with cervical uterine lesions produced by human papillomavirus.

We studied 30 women with cervical lesions that showed human papillomavirus infection (HPV). Cervical HPV infection was diagnosed by cytology, histology, immunohistochemistry, and electron microscopy, as well as by DNA viral hybridization in situ with 6, 11, 16, and 18 HPV types. Three groups of patients were studied: 15 women infected by HPV of 6 and 11 types with koilocytic lesions and benign evolution, 15 women infected by HPV of 16 and 18 types with koilocytic lesions and malignant evolution, and 15 normal women without cervical lesions who served as controls. For each group, chromosome fragility was studied in peripheral blood lymphocytes. Aphidicolin (AP) was used as a clastogenic agent at a concentration of 0.12 microM. There were significant differences (p less than 0.001) between the control population and the patients affected by HPV. There were also significant differences (p less than 0.001) between the two groups infected with HPV. Our findings support the concept that chromosome fragility could serve as a cytogenetic marker to measure evolution, prognosis, and treatment of cervical lesion associated with HPV.

Adolescent↗
PubMed1992

Chromatin structure, DNA methylation, and gene expression at sites of viral integration in human fibroblasts. Implications for chromosomal fragility.

We analyzed the structural and functional properties of a chromosomal region in which a recombinant hybrid virus adenovirus 5/SV40 preferentially integrates. Our results demonstrated that the structure of the cellular targets for DNA and RNA viruses is very similar and that the cellular sequence flanking the integrated virus possesses, simultaneously, all the features postulated to be the molecular basis for chromosomal fragility.

Adenoviridae↗
PubMed1990

Chromosome fragile sites in Down syndrome patients.

We report on the fragile site expression in lymphocytes from 16 Down syndrome (DS) men aged 24 to 52 years. Among rare fragile sites, 16q22 has been reported to be induced or enhanced by alpha-interferon. Since DS cells have three copies of the receptor for alpha-interferon, we hypothesized a possible enhancement of 16q22 expression. This fragile site has also been related to a specific rearrangement in M4 acute nonlymphocytic leukemia. In view of the high incidence of acute leukemia in DS subjects, we studied the expression of 16q22 in lymphocyte cultures treated with 5-bromodeoxyuridine or alpha-interferon. We also studied whether the repair deficiency of DS cells could affect the expression of aphidicolin-induced fragile sites. The level of chromosomal aberrations was compared with that found in aphidicolin-treated cultures from 12 normal subjects of the same age. We found neither spontaneous or BrdU-induced fragility at 16q22 nor induction by alpha-interferon. Chromosomal breakage rate was increased in alpha-interferon-treated cultures in comparison with control cultures of the same subjects. Aphidicolin-induced fragile sites expression in DS patients did not differ significantly from that found in the lymphocyte cultures from control subjects.

Adult↗
PubMed1991

Preferential integration of marker DNA into the chromosomal fragile site at 3p14: an approach to cloning fragile sites.

Fragile sites are specific regions of chromosomes that are prone to breakage. In cells cultured under conditions that induce fragile site expression, high levels of inter- and intrachromosomal recombination have been observed involving chromosomal bands containing fragile sites. To determine whether expression of specific fragile sites would facilitate preferential integration of exogenous DNA at these recombination hot spots, the vector pSV2Neo was transfected into a Chinese hamster-human somatic cell hybrid containing a derivative chromosome 3 as its only human component. Chromosome 3 contains a common fragile site at band 3p14.2 (FRA3B) that is induced by aphidicolin. Both cells induced to express FRA3B and the uninduced control cells were transfected with the pSV2Neo selectable plasmid. In situ hybridization of a biotin-labeled pSV2Neo probe to metaphase chromosomes revealed one to three integration sites in each stably transfected clone. Four of 13 clones transfected under conditions of FRA3B induction showed integration of pSV2Neo at 3p14; these clones also showed specific integration into hamster chromosome 1 and a rearranged chromosome characteristic of CHO cells (mar2). The 7 control clones, however, showed an apparently random pattern of pSV2Neo integration. Significant hybridization of pSV2Neo to both FRA3B and Chinese hamster chromosomes 1 and mar2 was seen in 100 cells from pooled colonies transfected after treatment with aphidicolin. These results suggest that preferential integration of marker DNA into human and Chinese hamster fragile sites occurs with exposure to aphidicolin. The nature of the DNA sequences at fragile sites is unknown and, despite a number of approaches, these sequences have not yet been isolated; our procedure may represent an approach to the cloning of fragile sites.

Animals↗
PubMed1992

[Chromosomal restructurings and the distribution of chromosome fragile sites in the peripheral blood lymphocytes in a breast cancer patient after cytostatic therapy].

Cytogenetic analysis was performed repeatedly on a breast cancer patient since the beginning of the antitumor treatment. Double minute chromosomes (DMS, 2-10 per cell) were found in less than 2% of peripheral blood lymphocytes besides other chromosomal abnormalities after radiation therapy and 8 months after chemotherapy. The level of structural chromosomal aberrations two years after the therapeutic treatment was 0.13-0.14 aberrations per cell, but DMS were not observed. Estimation of the fragile site (FS) frequency and distribution at this time revealed a significant expression of the common FS FRAGF (9q1.2) after the treatment of blood culture with 5-bromo-2-deoxyuridine at dose levels of 7 and 50 g/l and enhanced fragility in chromosome band 1p35-36.1 (FRA1A) in folate-deprived conditions. Rare FS were not found. The presented data are discussed.

Antineoplastic Combined Chemotherapy Protocols↗