PubMed Health⌕ Search

Biomedical subjects

G M Martin

Publications and source records attributed to G M Martin.

At least 181 records · Page 10Linked to original sources
PubMed1980

Effects of chromosome constitution on growth and longevity of human skin fibroblast cultures.

Employing standardized cell-culture methods, 10 euploid and 22 constitutionally aneuploid human skin fibroblast strains were assessed in triplicate for total growth potential, growth rates, population-doubling times, and cloning. In addition, longitudinal growth rate studies were carried out with otherwise isogenic 45,X and 47,XXX clonal cultures derived from a mosaic parental strain. Growth rates and longevities were cell-strain specific and highly reproducible among sister cultures of a given strain. There was no systematic correlation between chromosome constitution and any of the measured growth parameters. Trisomic as well as monosomic strains showed the same degree of variability with respect to these parameters as did euploid cultures. In particular, 4 trisomy 21 strains were not unusually short-lived, nor were clones with the 47,XXX constitution compared to those with 45,X karyotypes. We therefore conclude that the cumulative number of in vitro doublings preceding senescence of fibroblast-like cells cultured from skin does not differ significantly among cultures derived from humans who have a normal karyotype, trisomy 13, 18, or 21, the 45,X constitution, or various combinations of extra X and Y chromosomes.

Aneuploidy↗
PubMed1980

Genotropic theories of aging: an overview.

We have considered a rather wide-ranging number of genotropic theories of aging, defined as those which specify genomic alterations as the key to the understanding of the mechanisms of senescence. The fifteen ideas we have discussed are listed in Table 1, which divides them, in a rather arbitrary fashion, into two broad classes--those which emphasize modifications in gene structure and those which emphasize modifications in gene expression. It seems probable that no single one of these ideas will emerge as "the" underlying mechanism of aging, but that many of them will prove to have some credence. The aging process most certainly is under highly polygenic controls. In the case of human beings, I have made crude estimates [33] based upon a analysis of the phenotypes of known or suspected alleles at 2,336 genetic loci and the assumption of an upper limit for man of 100,000 informational loci, that anywhere from about 70-7000 genes could in fact be involved. This should not discourage us from pursuing a search for those loci which may be of profound importance to human aging as it ordinarily occurs in most human beings. In my opinion, however, the most pressing short-term need for biomedical gerontologists is to discover biochemical genetic reasons to explain why certain individuals seem especially prone to one or another of the age-related debilities, such as cancer, the various forms of arteriosclerosis, diabetes mellitus, osteoporosis, osteoarthritis, senile cataracts and senile dementia. Therefore, in my view, the future of progress in geriatric medicine is likely to be closely coupled to progress in medical genetics and genetic pathology.

Aging↗
PubMed1980

Differential use of food and water cues in the formation of conditioned aversions by domestic chicks (Gallus gallus).

The differential use of cues in the formation of conditioned aversions to food and water by domestic chicks was examined. Aversions were more readily demonstrated to red food than to red water, and taste was found to be an adequate cue with water but not with food (Experiments 1-5). It is suggested that such asymmetry mitigates the usefulness of the concept of "belongingness" and can more profitably be viewed as a function of the particular response topographies adopted with respect to food and water. The sixth experiment demonstrated that aversions for colored water could be readily demonstrated when the response topography for drinking was manipulated to ensure the utility of visual cues in selecting fluids. These findings are discussed with respect to a general process approach to conditioned aversion learning.

Animals↗
PubMed1980

Graduate medical education and certification in physical medicine and rehabilitation.

The American Board of Physical Medicine and Rehabilitation has certified 1608 physiatrists as diplomates, of whom 377 were certified in the years 1977 through 1979. For the 1979-1980 educational year, 516 of 608 residency positions were filled. Demographic analysis indicates 43% women and 52% foreign medical graduates (FMG) with an increasing female-to-male ratio and a decreasing ratio of FMGs to American medical graduates (AMGs). On the basis of proposed indices of productivity and quality and of results in the certifying procedures, the 62 currently accredited training programs show a wide distribution of effectiveness. A majority of programs are of good quality and are productive. A significant number apparently have problems that warrant critical self-analysis of all aspects of the educational endeavor. Increased productivity is needed in view of the shortage in the number of persons working in the specialty. Attention should center on recruitment and appointment of good residents, building of strong and effective faculties, and provision of stimulating, balanced educational experiences. Evaluation of competence is a dual function of the training programs and the specialty boards and is currently undergoing in-depth study under the sponsorship of the American Board of Medical Specialties (ABMS).

Certification↗
PubMed1979

Aversive properties of cycloheximide versus memory inhibition in chickens' formation of visually cued food aversions.

No memory inhibition for a conditioned aversion in chickens, produced by pairing a novel colored food and lithium chloride (LiCl), was found when cycloheximide (CXM) was injected intracerebrally (IC) two or six hr before feeding. Good conditioned aversions were found when CXM alone was injected IC following consumption of the novel food. No aversions were found when CXM alone was injected IC two hr before feeding. Possible reasons for apparent memory inhibition using CXM in some appetitive paradigms are discussed.

Animals↗
PubMed1979

Changes in cholesterol metabolism with dietary cholesterol in children with familial hypercholesterolaemia.

1. Possible defects in cholesterol metabolism were sought in children with familial hypercholesterolaemia. 2. In nine affected children (eight heterozygotes and one homozygote) and in five healthy children, cholesterol synthesis and bile acid synthesis were determined from the excretion of steroids in the faeces during a low cholesterol diet. Cholesterol synthesis of 10.1 +/- 4.4 mg day-1 kg-1 in the hypercholesterolaemic children was similar to that in these and other normal children. Mean bile acid synthesis of 4.0 +/- 2.1 mg day-1 kg-1 also resembled normal values though three severely affected heterozygotes excreted substantially less. 3. The response to 4 weeks' additional 450 mg of dietary cholesterol/day led to variable changes in the plasma cholesterol and in the sterol balance. On average the affected children showed a rise in plasma cholesterol which resembled that in healthy subjects. The sterol balance fell in most, suggesting a reduction in cholesterol synthesis, which is the normal response to dietary cholesterol. 4. The response to dietary cholesterol was therefore at least qualitatively similar in the hypercholesterolaemic children to that reported in healthy subjects.

Adolescent↗
PubMed1979

Cellular aging in Werner's syndrome: a unique phenotype?

Werner's syndrome is commonly regarded as a model for the study of premature aging. There are, however, a variety of clinical and pathologic anatomical features that clearly distinguish it from aging in normal individuals. In this paper we report on in vitro cytogenetic and cell fusion studies that indicate cultured fibroblast-like cells derived from Werner patients differ from cells of normal donors. Despite these discordances with "natural" aging, however, Werner's syndrome, like several other "segmental progeroid syndromes," may prove useful for the investigation of selected aspects of the aging process and of age-related diseases.

Adult↗
PubMed1979

Genetic and evolutionary aspects of aging.

Four questions of fundamental importance to gerontology are considered. 1) The number of genes involved in aging--in the case of man, an analysis of the phenotypes of relevant spontaneous mutants indicates that aging is highly polygenic. 2) General categories of genes--regulator genes may be more relevant than structural genes: a) three aneuploid disorders, Down's, Turner's and Klinefelter's syndromes, ranked among the top 10 candidates as "segmental progeroid syndromes" when compared with 162 single gene disorders of relevance to the pathobiology of aging; b) the rates at which maximum life spans have been increasing, especially among hominids, have probably been too rapid to be accounted for by changes in the amino acid sequences of proteins; c) a preliminary analysis of the variance of maximum life spans among a few orders of mammals is suggestive of a linear correlation with the indexes of rates of chromosomal evolution, as estimated by Bush et al. (Proc. Natl. Acad. Sci. USA 74: 3942-3946, 1977). 3) Nature of gene action--although there are reasons for invoking genes that modulate the rates of accumulation of somatic mutations, differential regulation of development is likely to be a major setting for gene action. 4) New approaches to formal genetic analysis of aging--advances in experimental embryology and somatic cell genetics offer such opportunities.

Aged↗
PubMed1979

SV40 T-antigen expression in cultured fibroblasts from patients with Down syndrome and their parents.

Expression of simian papovavirus 40 (SV40) T-antigen following in vitro infection was studied in skin fibroblasts from patients with Down syndrome (DS) and their parents to determine whether the increased susceptibility to SV40 infection reflected the cytogenetic defect or the leukemia risk associated with this syndrome. As a group, fibroblasts from patients with DS showed elevated T-antigen expression 72 hrs after infection compared to that of a healthy control population. However, among 24 patients tested, the cell lines of only 11 showed statistically significant increases in T-antigen expression. A cell line from a patient with concurrent DS and acute myelogenous leukemia had a normal value. T-antigen expression did not correlate with the percentage of cells trisomic for chromosome 21 in 18 cell lines examined or with the number of copies of this chromosome in disomic and trisomic cell strains cloned from three mosaic patients.Collectively, cell lines from parents of trisomy 21 patients also showed increased susceptibility to SV40 infection; however, in five families tested, a consistent pattern of genetic transmission of elevated T-antigen expression from parent to offspring was not observed. Q-banding of cell lines in one family showed that elevated T-antigen expression is not a marker of parental nondisjunction. Variation in susceptibility to human interferon, an antiviral agent, did not account for variation in T-antigen levels among these cell lines. Thus, the abnormalities of T-antigen expression in DS appear independent of the hyperdiploid state and are not a sensitive indicator of cancer risk.

Antigens, Viral↗
PubMed1978

Evidence for clonal attenuation of growth potential in HeLa cells.

The growth of primary clones and serial subclones of HeLa cells and of diploid human fibroblast-like cells were compared both in the presence and absence of feeder layers; the latter had no significant effects upon the results. Clones and subclones of both cell types displayed great heterogeneity in growth rates, typically with a bimodality of growth distributions. Serial passages of clones selected on the basis of superior rates of proliferation showed attentuation of growth potentials; the extent of such attentuations was much less in the case of HeLa cells, suggesting at least one possible basis for the differences in long-term growth potential between these two classes of cell lines.

Cell Division↗
PubMed1978

The replicative life spans of euploid hybrids derived from short-lived and long-lived human skin fibroblast cultures.

Two recent technical advances facilitate the derivation of proliferating hybrids from human diploid fibroblast strains without recourse to biochemical selection: (1) a new chemically-mediated method of somatic cell fusion (PEG-DMSO) yields hybrids at rates as high as 1 in 160 colonies after dilute plating of treated cell mixtures, and (2) a simple technology for assessment of DNA content (flow microfluorometry) permits rapid and highly sensitive monitoring of ploidy. Employing these techniques, we isolated 43 chromosomally stable hybrid clones from 12 crosses between seven different strains representing a wide range of longevities. Crosses between short-lived strains resulted in short-lived hybrid offspring, whereas hybrids derived from long-lived parents tended to be long-lived. Crosses between strains of contrasting longevities gave clones with intermediate growth potentials relative to the other types of hybrids. The failure to observe complementation (enhanced longevity) of hybrids argues against random recessive single-copy gene mutations as important determinants of clonal senescence.

Cell Fusion↗