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D R Cox

Publications and source records attributed to D R Cox.

At least 145 records · Page 8Linked to original sources
PubMed1982

Production of viable adult trisomy 17 reversible diploid mouse chimeras.

Aneuploid mouse embryos and fetuses are an important system for investigating the pathogenesis of the developmental and functional consequences of chromosome imbalance in mammals. However, the fact that almost all mouse aneuploids die in embryonic or fetal life restricts their usefulness for studies of loci and functions that are expressed only after birth. As an approach to rescuing aneuploid cells, we have prepared chimeras by aggregating aneuploid embryos with diploid embryos at the 8-16 cell stage. This technique has allowed us to produce trisomy 17 reversible diploid (Ts17 reversible 2n) chimeras containing cells of a trisomic state, which is ordinarily lethal at 10-12 days of gestation. All of the analyzed organs from the chimeras, including brain, liver, kidney, lung, muscle, heart, thymus, spleen, bone marrow, blood, and skin, contained both Ts17 and 2n cells. The proportion of Ts17 cells in each organ as estimated from coat color, enzyme markers (glucosephosphate isomerase), and karyotypes ranged from 5% to 85%, most commonly 20-40%. This is in contrast to the control 2n reversible 2n chimeras in which the 2n component on the same genetic background as the Ts17 generally comprised 60-90% of the cell population. The growth rates of the living Ts17 reversible 2n chimeras were in the lower half of the normal range, and the oldest animals are now age 14 mo. No progeny were obtained from Ts17 germ cells in the two fertile T217 reversible 2n chimeras. In comparison with analogous human situations, it is striking that, except for a kink in the tail of one living animal, none of the Ts17 reversible 2n chimeras had any discernible structural abnormalities. Our findings indicate that it is feasible to rescue cells from autosomal aneuploidies that otherwise result in early fetal death.

Aneuploidy↗
PubMed1982

Assignment of the gene for beta 2-microglobulin (B2m) to mouse chromosome 2.

We have assigned the gene (B2m) coding for murine beta 2-microglobulin (B2M) to mouse chromosome 2 by using a novel panel of Chinese hamster-mouse somatic cell hybrid clones. Because of 35 independent primary hybrids used in this study were derived from two types of feral mice, each with a different combination of Robertsonian translocation chromosomes, as well as from mice with a normal complement of acrocentric chromosomes, analysis of 16 selected mouse enzyme markers provided data on the segregation of all 20 mouse chromosomes in these hybrids. Mouse B2M was identified in cell hybrids by immunoprecipitation with a species-specific anti-mouse B2M antiserum followed by two-dimensional polyacrylamide gel electrophoresis of the immunoprecipitated polypeptides. Enzyme analysis of the segregant clones excluded all chromosomes for B2m assignment except mouse chromosome 2, and karyotype analysis of nine informative hybrid clones confirmed the assignment of B2m to this chromosome. These results demonstrate that, in the mouse, as in man, B2m is not linked to the major histocompatibility or immunoglobulin loci.

Animals↗
PubMed1982

Some aspects of analysis of covariance.

An account from first principles is given of a number of aspects of analysis of covariance. Six different meanings of analysis of covariance are outlined and the history of this technique is sketched briefly. The development of the key formulae from the method of least squares is described, and generalizations to other distributions in the exponential family are mentioned. Special problems of application in randomized experiments and in observational studies are discussed. Finally, the decomposition of regression relations is considered along with components of covariance.

Analysis of Variance↗
PubMed1981

Assignment of genes to the human X chromosome by the two-dimensional electrophoretic analysis of total cell proteins from rodent-human somatic cell hybrids.

The technique of two-dimensional (2-D) gel electrophoresis was sued to identify five human X-linked gene products in crude cell extracts of mouse-human and Chinese hamster-human somatic cell hybrids. The human origin of these five polypeptides was demonstrated by their comigration with human fibroblast proteins and their failure to comigrate with polypeptides in extracts from the mouse or hamster parental cells. All five polypeptides were present in extracts of rodent-human hybrids that contained a human X chromosome, but were not found in extracts of cells that lacked a human X chromosome. Chromosome analysis of the hybrid clones revealed that the human X chromosome is both necessary and sufficient for the expression of the five polypeptides, designated pX-24, pX-27, pX-37, pX-40, and pX-56. pX-56 can be identified as the human X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD) (E.C.1.1.1.49), while polypeptides pX-24, pX-27, pX-37 and pX-40 have molecular properties unlike those of known human X-linked gene products. pX-24 appears to be a membrane-bound protein that maps to the distal portion of the long arm of the human X chromosome, while pX-27, pX-37, and pX-40 are soluble proteins that map to the proximal long arm or to the short arm of the human X chromosome. 2-D gel electrophoretic analysis of extracts from somatic cell hybrids provides a general method for identifying polypeptides in crude cell extracts coded for by any specific chromosome and can be used to study primary gene products not previously amenable to genetic analysis.

Animals↗
PubMed1980

Genes coding for sensitivity to interferon (IfRec) and soluble superoxide dismutase (SOD-1) are linked in mouse and man and map to mouse chromosome 16.

By using 12 hamster-mouse hybrids segregating a mouse T(16;17)Bnr Robertsonian translocation chromosome in conjunction with 10 similar hybrids segregating normal mouse chromosomes, we have shown that the loci that control cellular sensitivity to interferon (IfRec) and code for the soluble enzyme superoxide dismutase (SOD-1) (superoxide:superoxide oxidoreductase; EC 1.15.1.1) are syntenic in the mouse and map to mouse chromosome 16. IfRec and SOD-1 are also syntenic in man. They have previously been assigned to the distal segment of the long arm of human chromosome 21, trisomy for which causes Down syndrome. Because both IfRec and SOD-1 map to mouse chromosome 16, it will now be possible to use mice trisomic for this chromosome to determine whether certain aspects of the Down syndrome phenotype in man are caused by an altered dosage of IfRec and SOD-1.

Animals↗
PubMed1977

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.

Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses.

Drug Evaluation↗
PubMed1976

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design.

The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers, reporting the results in the medical literature. One unreported result which deserves such publication is the development of the expertise to design and analyse such trials. This report was prepared by a group of British and American statisticians, but it is intended for people without any statistical expertise. Part I, which appears in this issue, discusses the design of such trials; Part II, which will appear separately in the January 1977 issue of the Journal, gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test, including a worked example, and discusses the interpretation of trial results, including brief reports of 2 particular trials. Both parts of this report are relevant to all clinical trials which study time to death, and wound be equally relevant to clinical trials which study time to other particular classes of untoward event: first stroke, perhaps, or first relapse, metastasis, disease recurrence, thrombosis, transplant rejection, or death from a particular cause. Part I, in this issue, collects together ideas that have mostly already appeared in the medical literature, but Part II, next month, is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration. Such trials include the majority of all clinical trials of cancer therapy; in cancer trials,however, it may be preferable to use these statistical methods to study time to local recurrence of tumour, or to study time to detectable metastatic spread, in addition to studying total survival. Solid tumours can be staged at diagnosis; if this, or any other available information in some other disease is an important determinant of outcome, it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive, and more intuitively satisfactory, for it will then only be necessary to compare like with like, and not, by chance, Stage I with Stage III.

Clinical Trials as Topic↗
PubMed1971

Specific detection of antigen-binding cells by localized growth of bacteria.

A new method for the enumeration of lymphoid cells with specific surface-receptors for antigen is described, based on the use of beta-D-galactosidase (EC 3.2.1.23), either directly as an antigen or as a conjugated antigen. Binding of beta-D-galactosidase is revealed by its activity in releasing riboflavin from a synthetic substrate, riboflavin-beta-D-galactopyranoside. The riboflavin, inactive as a vitamin in the galactosidic form, becomes active when released by the enzyme, and can be detected by bioassay. Hence, lymphoid cells with receptors for beta-D-galactosidase on their surface can be detected after they have been exposed to the enzyme, washed, and then plated in agar containing riboflavin-beta-D-galactopyranoside, streptomycin, riboflavin-deficient medium, and a streptomycin-resistant strain of Streptococcus faecalis that requires riboflavin. Release of riboflavin is signalled by the growth of characteristic bacterial colonies over the cell that bound beta-D-galactosidase.

Animals↗