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Biomedical subjects

J H Ford

Publications and source records attributed to J H Ford.

At least 19 recordsLinked to original sources

Detection of chromosome 17- and X-bearing human spermatozoa using fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) with DNA probes specific to chromosomes 17 and the X has been applied to human ejaculated sperm. After sperm nuclei were decondensed with EDTA and DTT, biotinylated alpha satellite DNA probes TR17 and TRX were separately used on preparations from thirteen healthy donors. After hybridization 96% of sperm were labelled with the TR17 probe and 48% of sperm were labelled with the TRX probe. Frequencies of 0.33% disomic 17 and 0.29% disomic X sperm were found. The frequencies of diploid sperm were assessed as 0.37% using the TR17 probe and 0.20% using the TRX probe which labelled only one half of the sperm; after correcting the result from the X-probe to 0.40% the two frequencies are very similar.

Aneuploidy

Chromosome errors at mitotic anaphase.

Errors in mitotic divisions were assayed using various satellite DNAs as probes, hybridized in situ, to show that they included nondisjunction, chromosome and chromatid lagging, chromatid malsegregation, and monopolar segregations. The total rates of error were 1.7, 1.1, and 0.6% for chromosomes X, 17, and 18, respectively. Lagging was the most common error for all chromosomes and chromatid malsegregation, a source of 3:1 segregations occurred at about the same frequency as nondisjunction. In some cells, lagging of both X chromatids occurred and there were several cells where both X chromosomes showed errors in segregation. The disjunction of chromosomes was shown to be independent of their segregation and is speculated to involve a different mechanism.

Anaphase

Localization by in situ hybridization of a type I keratin intermediate filament gene (Krt-1.14) to band D of mouse chromosome 11.

A probe from the 3' noncoding region of a murine type I keratin intermediate filament (IF) gene (Krt-1.14) localizes to band D of murine Chromosome 11 using in situ hybridization. This localization provides a physical confirmation of the assignment of the type I keratin genes by linkage analysis in the mouse. It also demonstrates that the Krt-1.14 genes are at a single locality in the mouse in contrast to the two locations on the short and long arms of chromosome 17 in humans.

Animals

Centralized telemetry monitoring: implementation and management.

Baptist Memorial Hospital in Memphis, Tennessee has implemented a newly designed cardiac arrhythmia monitoring system. Management engineers worked closely with nurses and physicians in the design process which led to development and implementation of a centralized telemetry monitoring system. Changes in the work distribution, improvement of the work environment, efficient use of nursing personnel and upgrades of monitoring equipment are several of the objectives addressed by this new centralized monitoring system. The backbone of the centralized telemetry monitoring system is an effective communication system that fully addresses staff needs during emergency situations. This paper presents the communication system features as well as the operational, functional and technical considerations necessary to support a centralized telemetry monitoring system. Some topics covered in detail include communication system selection, staff scheduling, selection, training, and supervision of staff members, ergonomic workstation design parameters and centralized telemetry monitoring system benefits. One benefit observed was that an additional 35 minutes per nurse per shift was made available to provide additional patient care activities.

Arrhythmias, Cardiac

Novel translocations in acute nonlymphocytic leukemia. Two cases involving chromosome 21, band q22.

We present two cases in which translocations involving 21q22 were found at presentation in acute nonlymphocytic leukemia (ANLL). The first of these translocations, t(3;21)(q26-q27;q22), is previously unknown in ANLL, but appears indistinguishable from that reportedly associated with Philadelphia-positive chronic myelogenous leukemia. The second case involves t(15;21)(q21-q22;q22), a translocation previously undescribed in ANLL. Both of these exchanges involve 21q22 plus another chromosome region associated with leukemogenesis. We attempted to interrelate these cytogenetic data with the oncogenic significance of 21q22.

Chromosome Banding

Chromosome elimination in micronuclei: a common cause of hypoploidy.

An excess of hypoploid cells has repeatedly been reported in studies of aneuploidy and has often been attributed to technical artifact. We have examined at least 200 anaphase or early-telophase cells from each of 28 normal women and found that chromosome or chromatid lagging occurs in an average of 2.43% of cells. In a separate study, we have examined the frequency of micronuclei in cytochalasin B-arrested, binucleate cells and shown that a similar frequency of cells (1.6%) contain one or more micronuclei. Using in situ hybridization of an alpha centromeric probe (alpha R1), which hybridizes to 9 of the 22 human autosomes, we were able to infer that most, if not all, of the micronuclei contain whole chromosomes or chromatids. Since the loss of a chromosome by lagging will induce hypoploid daughter nuclei (two where a chromosome is lost and one where a chromatid is lost), we conclude that lagging is a major mechanism for chromosome loss in human lymphocyte cultures. This loss occurs in the cells of normal individuals under control conditions.

Anaphase

Chromosome flexion: potential for assessing the state of spindle assembly.

A novel measurement, that of chromosome flexion, has been used to assess the degree of spindle polymerization at metaphase in human lymphocytes. It was found that this measurement showed a highly repeatable quantitative response to nocodazole exposure. Thus this measurement could be used to assess the potential for chemicals to depolymerize spindles. Under controlled conditions, individual differences were observed between the subjects which might be related to their age. However, the response to nocodazole-induced spindle depolymerization, as measured by flexion, was uniform for all subjects. 4 chemicals reported to induce aneuploidy in mammalian cells were used in a flexion assay. Only substances known to depolymerize microtubules reduced chromosome flexion.

Adult

Rapid induction of anaphase in competent cells by hypotonic treatment.

After brief exposure to hypotonic solutions cultures of human lymphocytes and PtK2 cells revealed a significant increase in the frequency of anaphase cells. Hypotonic solutions of potassium chloride, sodium chloride, sodium citrate and dilute culture medium all induced a flux of anaphase A after 30 sec treatment. PtK2 cells were able to proceed through to anaphase B and telophase after hypotonic treatment but human lymphocytes were arrested in anaphase A unless ATP was added to the hypotonic solution. In the experimental regime which was used, neither treatment with nocodazole nor the calcium ionophore A23187 was able to mimic the response to the hypotonics, and it is suggested that the primary induction of anaphase may involve a change in the kinetochore. Brief hypotonic treatment of actively growing cultures provides a simple method of increasing the frequency of anaphase cells for use in various investigations.

Adenosine Triphosphate

A complex translocation in acute promyelocytic leukemia.

The breakpoints of a complex three-way translocation involving chromosomes X, #15, and #17 were resolved in a case of acute promyelocytic leukemia (APL). It is now apparent that similar cases of variant chromosome translocations are found in both chronic granulocytic leukemia (CGL) and APL. The morphological and clinical findings in this case emphasize the variability found in some cases of APL.

Chromosomes, Human, 13-15

Differences in the error mechanisms affecting sex and autosomal chromosomes in women of different ages within the reproductive age group.

Aneuploidy was assessed in lymphocyte cultures from 16 women aged between 20 and 50. Between 236 and 1,677 cells were studied per subject and the gains and losses of each chromosome recorded. The X chromosome was found to show the same ratio of loss to gain (approximately 3:1) at all ages, but the frequency of total aneuploidy (loss plus gain) showed a significant increase with age. By contrast, there was no clear association of the frequency of autosomal chromosome aneuploidy with age, but the ratio of loss to gain was significantly greater in younger women (aged 21-35) than in older women (aged 36-50). Thus, X chromosomes in females are affected by a mechanism of error different to that affecting autosomal chromosomes. Although the ratio of loss to gain changes, the relative involvement of the different autosomal chromosomes is unchanged with age. Thus, the initial "recruitment" of chromosomes undergoing error is the same in both groups, but the "processing" of these chromosomes is different. Since the relative involvement of autosomes in aneuploidy mimics their relative involvement in displacement, it is proposed that displacement is the initial or "recruitment" step in error. "Processing" then commonly involves "chromosome elimination" in younger women and more frequent "random segregation" in older women.

Adult