Biomedical subjects

J H Ford

Publications and source records attributed to J H Ford.

At least 55 records · Page 3Linked to original sources

PubMed1984

Spindle microtubular dysfunction in mothers of Down syndrome children.

Trisomy 21, Down syndrome, is more prevalent in the children of older mothers and thus theories relating to its induction have suggested alterations in reproductive physiology, sexual performance, or accumulated errors as explanations. Such theories largely neglect observations demonstrating mitotic errors in the parents and families of children with Down syndrome, which suggest that a mechanism of chromosome error, basic to both mitosis and meiosis, may exist in Down syndrome parents. This paper describes such a mechanism of error and concludes that Down syndrome parents may have a condition of microtubular dysfunction which contributes to an increased rate of hyperploidy in all their dividing cells. It is suggested that sporadic microtubular dysfunction may occasionally be induced in otherwise "non-susceptible" individuals.

Adult↗

PubMed1984

Chromosome displacement and spindle tubule polymerization. 2. Effect of alterations of extracellular calcium on displacement parameters.

Human lymphocytes were grown for either the entire culture period of 72 h or the final 6 h of culture, in media with different concentrations of calcium. Cultures were harvested without colchicine or hypotonic treatment and 'displaced' chromosomes were analysed. Long or short term exposure to various concentrations of calcium gave similar results. The frequency of cells showing displacement and the median number of displaced chromosomes per cell were highly correlated with calcium concentration (r = 1). Only the smaller chromosomes, 13-22, showed a significant correlation for displacement rate and calcium concentration. Individual chromosomes showed a consistent response to calcium which appeared to be specific for each chromosome. Chromosome 17 was the most sensitive to calcium, but chromosomes 16, 19 and most C-group chromosomes showed no response. The acrocentric chromosomes 13, 14, 15, 21 and 22 all showed a modest but similar response. An hypothesis is advanced that these responses may be controlled by specific amounts of microtubular associated proteins and/or calmodulin in the spindle tubules attached to the different chromosomes.

Calcium↗

PubMed1983

Interactions between C-bands of chromosomes 1 and 9 in recurrent reproductive loss.

The size of the heterochromatic regions of chromosomes 1 and 16 was measured in a Test group of women with histories of recurrent spontaneous abortion and a Control group of fertile women. Measurements were made on Giemsa banded preparations and the euchromatic regions of 1q and 16q were used to correct for between-cell contraction. For each chromosome pair, the larger and smaller chromosome was identified and populations of each were compared between the two subject groups. For chromosome 1, the smaller chromosome of the Test group was significantly smaller than that of the Control group (P less than 0.001) and the size of the pair difference was larger in the Test than in the Control group (P less than 0.01). For chromosome 16, the smaller chromosome of the Test group was smaller than that of the Control group (5% level). The interaction of chromosome 1 and chromosome 9 heterochromatin in each individual has been analyzed. The combined score for the smaller chromosome 1 and the larger chromosome 9 shows a bimodal distribution and allows discrimination between the two subject groups. Various possible ways in which this interaction might affect reproductive outcome are discussed.

Abortion, Habitual↗

PubMed1983

Chromosome abnormalities in chronic lymphocytic leukemia revealed by TPA as a mitogen.

Bone marrow and peripheral blood cultures of chronic lymphocytic leukemia patients were mitogenically stimulated with TPA (12-O-tetradecanylphorbol-13-acetate). Clonal cytogenetic abnormalities were detected in frequencies varying from 15% to 100%, in five of the six patients studied. Parallel studies with pokeweek mitogen showed a much lower level of stimulation and only two abnormal clones were detected. The chromosome abnormalities described in this study are similar to those reported in CLL by other authors, particularly with respect to trisomy 12 and deletion 11q. A significant frequency of hypodiploidy and chromosome deletion was also detected in this study, and further studies are underway to determine the significance of these findings.

Adult↗

PubMed1983

Screening of karyotype and semen quality in an artificial insemination program: acceptance and rejection criteria.

Semen quality and karyotype were screened in all men offering to be donors for an artificial insemination (AID) program. The criteria for accepting or rejecting semen have now been set with respect to this sample of the population. There was no evidence of differences between the pregnancy rates of the accepted donors. One of 172 potential donors with a clear medical history had a chromosomal abnormality, 4 had pericentric inversions of chromosome 9, and 14 had other heterochromatic variants. Of the recipients of AID, 5 of 196 women had chromosomal abnormalities, and 12 had heterochromatic variants.

Adult↗

PubMed1983

Dermal necrosis and chromosome Iq abnormality in a man with a familial myeloproliferative disorder.

A 33 year old man, with pre-existing psoriasis and a family history of multiple occurrence of acute myeloid leukemia and other myeloproliferative disorders, developed steroid-responsive ulcerating skin lesions, pancytopenia, marrow hypoplasia, hyperglobulinemia and polyarthritis. An abnormal karyotype (47,XY + i(1q] was detected in the bone marrow, and comparison with a case previously reported by Lee et al. Suggested that this abnormality may be significant. His sister, who developed chronic leucocytoclastic vasculitis, had pre-existing psoriasis, variable mild leucopenia and marrow dysplasia. Review of available records of other affected family members documented the occurrence of steroid responsive pancytopenia, knee swelling and terminal lipoid pneumonia in a first cousin. Four other relatives died with acute myeloblastic leukemia and another died with myelofibrosis. Two healthy first degree relatives were subjected to laboratory investigations with essentially negative findings.

Adolescent↗

PubMed1983

Displacement of chromosomes in mitosis: a technique for assessing differential chromosome error.

To assess whether displacement--the appearance of individual chromosomes inside of the ring of chromosomes attached to spindle fibers--is a valid method of analyzing chromosome misdivision, displacement data from six healthy female subjects were compared with data for mitotic and meiotic nondisjunction. Statistical analysis indicated that nondisjunction and displacement are equivalent methods of assessing differential chromosome error. Tests for homogeneity of the data sets showed no significant heterogeneity for the mitotic data, but chromosomes 1, 2, 11, 16, 17, 19, and 20 were responsible for significant heterogeneity in the meiotic data.

Adult↗

PubMed1983

Chromosome displacement and spindle tubule polymerization: 1. The effect of alterations in pH on displacement frequency.

In order to test whether 'chromosome displacement' (Ford and Lester, 1982) is related to spindle function, the phenomenon was examined under conditions known to alter spindle tubule polymerization, namely alterations in pH within the range 6.8-8.0. The following observations were made: (a) the frequency of cells showing chromosome displacement was not altered by variations in pH, but the number of displaced chromosomes per cell was markedly changed. Minimum numbers of chromosomes were displaced at pH 7.6. (b) For any chromosome, the extent of the response to pH change, was positively correlated with the basal displacement rate for that chromosome. (c) Chromosomes which have a 'stable' evolutionary history have a more predictable response to pH than those which have an 'unstable' history. Since displacement is significantly influenced by pH, it is concluded that the phenomenon is related to spindle structure.

Adult↗

PubMed1982

Within pair differences of human chromosome 9 C-bands associated with reproductive loss.

The size and position of the heterochromatic regions of chromosome 9 were examined in a group of women with histories of recurrent miscarriage and a control group of fertile women. Measurements were made on whole chromosomes (variability between chromosomes was taken to reflect differences in heterochromatin), and corrections for between-cell contraction were made by comparison with chromosome 7. Chromosomes were analysed in pairs and the following results were obtained: (1) The larger of the pairs of chromosomes of the test group were significantly larger than those of the control group: (2) The smaller of the pairs of chromosomes were the same in each group: (3) The differences between the chromosome pairs were significantly greater in the test than the control group: and (4) The sums of the homologous chromosomes were significantly greater in the test than in the control group. Independent assessment also showed that a significantly higher frequency of complete pericentric inversions of chromosome 9 was present in the test than the control group. These results are discussed in the light of two hypotheses: (1) The difference in the size of the homologous chromosomes is critical, and (2) the total heterochromatic content of a chromosome and/or cell is critical. Some evidence is presented to support each hypothesis, but the former is the more favoured by the data.

Centromere↗

PubMed1982

Factors affecting the displacement of human chromosomes from the metaphase plate.

In order to elucidate some of the factors influencing the attachment of chromosomes to spindles, an analysis was made of the displacement of chromosomes from the metaphase plate in preparations that received no colchicine or hypotonic treatment. Displaced chromosomes were identified by Giemsa banding. Three hypotheses were tested and led to the following conclusions: (1) Chromosomal displacement is a function of size--smaller chromosomes are displaced more often than larger ones. (2) The position of the centromere does not influence chromosome displacement. (3) The amount of centromeric heterochromatin in the chromosome has a highly significant effect on displacement--chromosomes with more heterochromatin are displaced more often than those with less.

Centromere↗

PubMed1981

Translocations involving chromosome 12. I. A report of a 12,21 translocation in a woman with recurrent abortions, and a study of the breakpoints and modes of ascertainment of translocations involving chromosome 12.

A translocation t(12;21)(q24.1;q21.5) is described in a woman with a history of recurrent spontaneous abortions. The break points of this translocation are compared with those of 30 other translocations described in the literature, and the following conclusions are drawn: 1) An excess of breaks occurs in the p arm of chromosome 12. 2) The distributions of breaks in the bands of chromosome 12 is significantly different from that expected on a random basis. 3) Translocations of chromosome 12 occur more often with chromosome 21 than any other chromosome, but these rearrangements do not involve a specific region of chromosome 12. 4) Most of the translocations were ascertained through their unbalanced meiotic products but seven translocations were "balanced". Of these "balanced" translocations, three individuals were abnormal and two were recurrent aborters. The concept that phenotypic outcome may be related to the gross structural characteristics of the translocation site is not supported in this study.

Abortion, Habitual↗

PubMed1981

Translocations of chromosome 12. II. A comparison of the distribution of sites of spontaneous and induced breakages.

Human chromosome 12 has been used as a model for studying the distributions of sites of induced and spontaneous breaks. The breakpoints were determined from (1) translocations involving chromosome 12, (2) spontaneous breaks in untreated cultures, (3) radiation-induced breaks, and (4) spontaneous breaks in Fanconi's anaemia. Statistical analysis showed discordance in the results both between the eleven individual bands and between the four assessments. Also, the distribution of breaks for all bands was significantly different from random in each assessment. Certain bands added considerable bias to the results, and when analysed individually, only four bands (p11.1, q13, q24, and p13) showed distributions over the four assessments that were significantly different from random. These four bands are Giemsa-negative bands, and two (p13 and q24) are adjacent to telomeres, while p11.4 is adjacent to the centromere. The fourth band, q13, is a known fragile site. It is concluded that bands adjacent to centromeres, which are not C-banded, are peculiarly sensitive to breakage. Telomeric bands are variable in their response to different conditions of breakage, and both the physical structure of the telomere and the specific gene sequences of individual telomeres are probably of importance in determining this response. The fragile site q13 responds as if breakage at this site is due to the base composition of the DNA.

Cells, Cultured↗

PubMed1981