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Biomedical subjects

S A Bruce

Publications and source records attributed to S A Bruce.

At least 37 records · Page 2Linked to original sources
PubMed1991

Longitudinal study of in vivo wound repair and in vitro cellular senescence of dermal fibroblasts.

A longitudinal study was performed to confirm the inverse relationship between in vivo age and in vitro proliferative capacity previously observed in a cross-sectional study, and to investigate the relationship between the growth of dermal fibroblasts in vitro and a physiological function (i.e., wound repair) that is known to decline with age in vivo. Fibroblast cultures were generated from skin punch biopsies from 12 male hamsters beginning at 1 month of age and at 6-months interval thereafter until the natural death of the animal. All cultures from all individuals exhibited finite proliferative capacity, and an inverse relationship was observed between donor age and maximum in vitro proliferative capacity. In addition, a direct correlation between the in vitro proliferative capacity of the dermal fibroblasts in vitro and the repair efficiency of the biopsy site was observed. However, these changes in the in vitro proliferative capacity and in vivo wound repair efficiency were not progressive beyond 12-18 months of age and were not indicative at any age of an individual's ultimate lifespan. This study provides evidence that in vitro proliferative capacity of dermal fibroblasts and in vivo wound repair may be comparable phenomena that share a common mechanism. However, the nonprogressive nature and the lack of correlation between these phenomena and the individual's ultimate lifespan indicate that their use as biological markers of aging is limited to animals younger than the mean lifespan of the species.

Aging↗
PubMed1991

In mice, the muscle weakness due to age is absent during stretching.

1. The contractile force was compared in isolated soleus muscles from young (2.5-8 months old) and aged (28-31 months old) mice. Force was measured at 25 degrees C during isometric tetanic contractions during isovelocity stretching and shortening contractions. 2. The normalized isometric force was lower by 13.3% in muscles from aged mice. Muscles from young and aged mice produced 0.951 +/- 0.031 N mg-1 (n = 12) and 0.824 +/- 0.048 N mg-1 (n = 9) respectively. The relaxation time, from 90 to 10% of the tetanic force, of muscles from aged mice was 102.1 +/- 3.7 ms (n = 6), which was longer than that for muscles from young mice, 84.4 +/- 3.8 ms (n = 6) (means +/- S.E.M.). 3. The force during shortening was also reduced in muscles from aged animals by the same proportion as the isometric force. Therefore the force during shortening relative to the isometric force was the same in muscles from young and aged mice. 4. During rapid stretching soleus muscles from aged mice produced a similar force to those from young mice. Therefore stretch can remove the weakness in muscles of aged mice. 5. These changes in muscles from aged mice are similar to those produced when inorganic phosphate (Pi) levels are raised, in skinned rabbit psoas fibres, or during fatigue or with low intracellular pH (pHi), in frog muscle. It is possible therefore that the force loss due to ageing may be due to a higher Pi level or a lower pHi.

Aging↗
PubMed1991

The successful medical management of gastric outflow obstruction associated with the use of non-steroidal anti-inflammatory drugs in the elderly.

One hundred and nineteen consecutive elderly patients with endoscopically diagnosed peptic ulceration were reviewed. Associated gastric outflow obstruction was present in 10.1%. The presenting clinical features differed significantly from typical younger patients and most (11/12) were taking non-steroidal anti-inflammatory drugs, suggesting a possible role for these agents in the pathogenesis of gastric outflow obstruction. These elderly patients have been successfully managed by medical therapy alone.

Aged↗
PubMed1990

Tumor promoters retard the loss of a transient subpopulation of cells in low passage Syrian hamster cell cultures.

Early passage normal diploid Syrian hamster (SH) fetal cell cultures contain a transient subpopulation of contact-insensitive (CS-) cells which lack density-dependent inhibition of cell division. The size of this CS- subpopulation decreases during in vitro passage by conversion of the CS- cells to contact-sensitive (CS+) cells. Approximately 10-15 population doublings after the frequency of the CS- cells has declined to below 0.001%, mass cultures cease proliferating and exhibit cellular senescence. Cultures with higher initial numbers of CS- cells exhibit longer in vitro proliferative life spans than cultures with smaller initial numbers of CS- cells. Active tumor promoting phorbol esters (12-O-tetra-decanoyl-phorbol-13-acetate [TPA] and phorbol-12,13-didecanoate [PDD]) retard the decline in the proportion of CS- cells during in vitro passage, while the inactive tumor promoting phorbol ester, 4 alpha-phorbol-12,13-didecanoate (4 alpha PDD) has no effect on the rate of loss of the CS- cells. In addition, continuous treatment from secondary culture with TPA or PDD extends by approximately twofold the in vitro proliferative life span of SH fetal cell cultures. Treatment must, however, begin at passage 1 or 2 when the CS- cells are still present. After the proportion of the CS- cells has decreased to less than 0.001% as in passage 6 cultures, promoters have no effect on the life span of the culture. This finding that exposure to promoters results in both a prolonged maintenance of the CS- cellular subpopulation, as well as an extension of in vitro proliferative life span, suggests that the conversion of CS- cells to CS+ cells is involved in the mechanism of in vitro senescence.

Animals↗
PubMed1990

Two classes of continuous cell lines established from Syrian hamster 9 day gestation embryos: preneoplastic cells and progenitor cells.

Primary cultures of 9-d-gestation Syrian hamster embryo (E9) cells are distinct from primary cultures of later gestational age in terms of their growth and differentiation. First, primary E9 cell cultures express multiple mesenchymal differentiation lineages (e.g., adipocyte, myoblast) only rarely seen in cultures of 13-d-gestation fetal (F13) cells. Second, although most primary E9 cultures have a limited in vitro proliferative life span and exhibit cellular senescence similar to primary cultures of F13 cells, E9 cultures seem to have higher frequency of escape from senescence and conversion to continuous cell lines compared to F13 cells. Moreover, this frequency can be further increased 4- to 5-fold by continuous exposure of the E9 cells to tumor promoters or epidermal growth factor. Eleven continuous cell lines have been isolated from untreated, promoter-treated, or epidermal growth factor-treated primary E9 cultures. Seven of these are neoplastic or preneoplastic. However, the remaining four do not show any evidence of being in neoplastic progression and three of these continue to express the same differentiated phenotype observed in ther parental primary cell cultures.

Animals↗
PubMed1990

Longevity and age-related pathology of LVG outbred golden Syrian hamsters (Mesocricetus auratus).

A colony of male Lakeview Golden (LVG) Syrian hamsters has been maintained for the last nine years as a source of various tissues for cellular aging studies. Observations on this colony also yielded data on survival time and physical and pathological manifestations of aging in this strain. Based on 150 spontaneous deaths, the median life span was found to be 19.5 months. The maximum life span was 36 months and the minimum 6 months. A cross-sectional pathological survey of sacrificed and spontaneously dying members of the population revealed a low rate of neoplasia and a variety of degenerative lesions that increased with age. These observations of a varied pathology and a low frequency of neoplasia provide justification for the continued development of the male LVG Syrian hamster as an animal model system for use in studies on the mechanism of both in vivo and in vitro aging.

Aging↗
PubMed1989

Dietary calcium, physical activity, and risk of hip fracture: a prospective study.

OBJECTIVE: To determine whether low dietary calcium intake and physical inactivity are risk factors for hip fracture among subjects aged 65 and over. DESIGN: Fifteen year follow up study of a large cohort of randomly selected elderly people living in the community, who had taken part in the 1973-4 survey of the Department of Health and Social Security, and for whom dietary and other data were recorded at initial interview and medical assessment. SETTING: Eight areas in Britain (England (five), Wales (one), and Scotland (two]. SUBJECTS: 1688 Subjects living in the community, of whom 1419 subjects (720 men and 699 women) agreed to participate. 1356 Subjects completed a seven day dietary record and 983 (542 men and 441 women) agreed to be assessed by a geriatrician. RESULTS: Incidence of hip fracture increased with age and was higher in women than men. Comparison with matched controls showed no evidence that the risk of hip fracture was related to calcium intake: the odds ratio for the lowest third of dietary calcium compared with the highest was 0.7 (95% confidence interval 0.1 to 3.9) after adjustment for smoking and body mass index. The adjusted odds ratio for the lowest third of outdoor activity compared with the highest was 4.3 (0.7 to 26.8), and that for grip strength was 3.9 (0.7 to 23.0). CONCLUSIONS: Reduced intake of dietary calcium does not seem to be a risk factor for hip fracture. Further evidence is provided that physical activity in the elderly protects against hip fracture.

Age Factors↗
PubMed1989

High-frequency 1H NMR studies of the effects of growth factors and phorbol esters on normal Syrian hamster diploid fibroblast cells.

The nuclear magnetic resonance (NMR) parameters, spin-lattice (T1), and spin-spin (T2) relaxation time, are usually longer for neoplastic cells than for normal cells of the same cell type. This has generally been true at low NMR frequencies (less than or equal to 100 MHz) when comparisons have been made between normal and neoplastic cells that have both spent a short time in culture. We have previously demonstrated that although the T1 values of paired normal and neoplastic Syrian hamster (SH) fibroblastic cells in culture are not significantly different when measured at 300 MHz, the 300 MHz T2 values for the neoplastic cells are smaller than those of the normal cells. (Xin et al. (1986), Cell Biophysics 8, 213.) Since treatment of normal diploid cells with polypeptide growth factors or tumor promoters frequently results in reversible expression of neoplasia-associated phenotypes, T1 and T2 were obtained at 300 MHz for treated and untreated SH cells to see if these compounds could also produce smaller 300 MHz T2 values. Secondary culture SH fetal fibroblast cells were treated with epidermal growth factor (EGF), fibroblast growth factor (FGF), phorbol-12,13-didecanoate (PDD) and 4-alpha-phorbol-12,13-didecanoate (4 alpha PDD). Treatment with either growth factor resulted in smaller T2 values, but a statistically significant decrease was not observed for PDD or 4 alpha PDD. The observed reductions in T2 values were correlated with the morphological and growth-stimulatory effects of these compounds on the cells.

Animals↗
PubMed1989

Effect of subnutrition on normalized muscle force and relaxation rate in human subjects using voluntary contractions.

1. Muscle weakness and wasting are well-known consequences of subnutrition, but there have been no published comparisons of these variables in a single muscle or muscle group. We report voluntary force measurements of adductor pollicis muscle in 11 subnourished patients normalized for their cross-sectional areas. We also report normalized relaxation rates of these contractions and the results are compared with those obtained in 40 healthy normally nourished subjects. 2. Normalized muscle force was no different in the subnourished group. However, relaxation rate was significantly slower than in the control group.

Adult↗
PubMed1989

Effect of age on voluntary force and cross-sectional area of human adductor pollicis muscle.

Muscle weakness accompanies ageing but its causes are still uncertain. We report maximum voluntary force measurements of adductor pollicis muscle, normalized for cross-sectional area, in twenty-three elderly subjects. Normalized force was lower in the elderly compared with a group of fifty-five young adult subjects by 27 +/- 4% (S.E.M.). This shows that atrophy alone is not the cause of the weakness of old age.

Adult↗
PubMed1987

Protective immunisation against hepatitis B with an internal antigen of the virus.

Preparations of hepatitis B virus (HBV) core antigen (HBcAg) synthesised in Escherichia coli have been shown previously to confer partial immunity against infection by the virus [Murray, Bruce, Hinnen, Wingfield, van Eerd, de Reus, and Schellekens: EMBO Journal 3:645-650, 1984]. In a further experiment reported here, immunisation of chimpanzees with a similar preparation of HBcAg that had been treated with sodium dodecyl sulphate in order to expose e antigen epitopes was found to protect one animal completely and another quite substantially upon challenge with the virus. The results are used to support the argument for trials in humans of a vaccine against HBV based upon or containing HBcAg and its e antigen derivative, and in discussion of a more general role for internal antigens in generating immunity against viral infection.

Animals↗
PubMed1987

Hyperthyroidism in elderly patients with atrial fibrillation and normal thyroid hormone measurements.

The results of a study to investigate possible underdiagnosis of hyperthyroidism in the elderly are reported. Four out of 24 patients with atrial fibrillation for which there was no obvious cause and who had normal thyroid hormone measurements were found to have subnormal thyrotropin responses to thyrotropin-releasing hormone and abnormal thyroid scans. The implications of this finding are discussed.

Aged↗
PubMed1986

NMR relaxation study of water protons in Syrian hamster fetal cells at 300 MHz.

The T1 and T2 relaxation times of water protons in two cell types in culture derived from Syrian hamster fetuses (normal primary or secondary fetal cells vs BP6T tumor cells derived from the normal cells transformed by carcinogens) were measured at 7.05 Tesla magnetic field (proton frequency = 300 MHz). The T1/T2 ratios and the correlation time, tau c, calculated from the T1/T2 ratio of cellular water protons, are significantly different in these two fibroblastic cell types of the same biological origin and with similar morphologies and growth rates in culture.

Animals↗
PubMed1986

In vitro senescence of Syrian hamster mesenchymal cells of fetal to aged adult origin. Inverse relationship between in vivo donor age and in vitro proliferative capacity.

Normal diploid Syrian hamster dermal mesenchymal cell strains, regardless of the age of the tissue of origin, exhibit in vitro cellular senescence. The frequency of spontaneous escape from senescence and conversion to a permanent cell line is less than 5% among replicate flasks. The overall pattern of senescence of cells of fetal, neonatal, young adult (6 months) and aged adult (24 months) origin is similar in terms of the morphological changes and proliferative changes indicated by the reduction of saturation density, cloning efficiency and [3H]thymidine labeling index and by the increase in population doubling time and cell volume. However, the average maximum cumulative population doubling level is characteristic for each cell type: 13-day gestation fetal cells, 28.6; neonatal cells, 18.7; young adult cells, 13.8; aged adult cells, 11.1. Thus, the in vitro proliferative capacity of Syrian hamster mesenchymal cells is inversely related to the in vivo age of the donor.

Aging↗
PubMed1985

A contact-insensitive subpopulation in Syrian hamster cell cultures with a greater susceptibility to chemically induced neoplastic transformation.

We previously have identified a subpopulation of contact-insensitive (CS-) cells which lacks density-dependent inhibition of cell division in primary and low-passage cultures of Syrian hamster embryonic (SHE) fibroblastic cells. Further, we have shown that the proportion of these CS- cells declines as a result of the stable phenotypic conversion of the CS- cells to contact-sensitive (CS+) cells. To determine whether these transient CS- cells are more sensitive to carcinogenic/mutagenic perturbation, the susceptibility to neoplastic transformation and somatic mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was examined in clonally isolated cell cultures containing various proportions of CS- cells (0.02-4%). The frequencies of morphological transformation, focus formation, and neoplastic transformation showed a positive correlation to the proportion of CS- cells in the treated cultures. In contrast, the frequency of MNNG-induced somatic mutation at the Na+,K+-ATPase locus was similar among cultures varying in their proportion of CS- cells. Thus, there is a transient subpopulation of CS- cells in primary SHE cell cultures that is more susceptible to neoplastic transformation although equally susceptible to induced point mutation. This dissociation between somatic point mutation and neoplastic transformation indicates a fundamental difference in the nature of these two phenomena. A possible relationship between the propensity of CS- cells (versus CS+ cells) to carcinogen-induced neoplastic transformation and the state of differentiation of the CS- cells is discussed.

Animals↗