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J Addison

Publications and source records attributed to J Addison.

30 records · Page 2Linked to original sources
PubMed1986

The pathogenicity of long versus short fibre samples of amosite asbestos administered to rats by inhalation and intraperitoneal injection.

For many years it has been accepted that fibre dimensions are the most important factor in the development of asbestos related disease with long fibres being more dangerous than short for all types of asbestos. This information has been derived from in vitro experiments and injection or implantation experiments since the kilogramme quantities of specially prepared dusts that are necessary for long term inhalation have not been available. The present study has taken advantage of the availability of a sample of amosite produced so that almost all fibres were less than 5 micron in length. The effects of this dust were compared to dust prepared from raw amosite that contained a very high proportion of long fibres. Previous data from studies with UICC amosite, which was intermediate in length, were also available for comparison. At the end of 12 months of dust inhalation, significantly more short fibre amosite was present in the lung tissue compared to the long but while the long fibre dust caused the development of widespread pulmonary fibrosis, no fibrosis at all was found in animals treated with short fibre. One third of animals treated with long fibre dust developed pulmonary tumours or mesotheliomas but no pulmonary neoplasms were found in animals treated with short fibre dust. Following intraperitoneal injection, the long fibre amosite produced mesotheliomas in 95% of animals with a mean induction period of approximately 500 days. With short fibre dust, only a single mesothelioma developed after 837 days. In previous inhalation studies with UICC amosite, relatively little pulmonary fibrosis had developed and only two benign pulmonary tumours. This would suggest that to produce a significant carcinogenic response in rat lung tissue amosite fibres must be longer than those in the UICC preparation. Following the injection of UICC amosite, however, mesotheliomas developed in the same proportion of animals and with the same mean induction period as with long fibre dust. From this it would appear that while very short fibres exhibit little carcinogenicity to either lung or mesothelial tissues, mesotheliomas can be produced by dust preparations consisting of shorter fibres than are needed to produce tumours.

Animals↗
PubMed1986

Inhalation and injection studies in rats using dust samples from chrysotile asbestos prepared by a wet dispersion process.

Long term inhalation studies and intraperitoneal injection studies in rats were undertaken with a series of chrysotile asbestos dusts. Three dust samples were generated from chrysotile modified by the wet dispersion process (WDC) and one was from unmodified chrysotile. Following a 1 year inhalation period, all the chrysotile samples proved extremely fibrogenic and carcinogenic and there were no significant differences between the WDC dusts and normal chrysotile. In all experimental groups approximately 25% of animals developed pulmonary carcinomas and in the oldest rats advanced interstitial fibrosis occupied on average 10% of all lung tissue. In the injection studies all the dust samples produced mesotheliomas in over 90% of animals. Very little chrysotile remained in the lungs of the animals that survived longest following dust inhalation and what there was was present as individual chrysotile fibrils. It is suggested that chrysotile is potentially the most harmful variety of asbestos as shown in these and other animal studies but that it is removed from lung tissue quite rapidly. In the long lived human species this may mean that except where exposure levels are very high and of long duration, chrysotile should be less hazardous than other asbestos types.

Animals↗
PubMed1985

Inhalation studies on the effects of tremolite and brucite dust in rats.

Samples of commercially used asbestos, especially chrysotile, are frequently contaminated by small amounts of other fibrous minerals. Among these are tremolite and brucite although pure tremolite is also produced commercially in relatively small quantities. In order to determine how harmful commercially exploited tremolite might be in comparison with other asbestos types and to explore the possibility that small amounts of tremolite and brucite as contaminants could significantly affect the pathogenicity of industrially used chrysotile, long-term animal inhalation and injection studies using rats were undertaken with what were considered to be mineralogically pure samples of these minerals. Rats treated with tremolite developed very high levels of pulmonary fibrosis as well as 16 carcinomas and two mesotheliomas in a group of 39 animals. Tremolite thus proved to be the most dangerous mineral that we have studied. Animals treated with 'brucite' developed moderate levels of pulmonary fibrosis and two carcinomas. Both tremolite and brucite produced mesotheliomas in greater than 90% of animals following i.p. injection. However, it was found that the supposedly pure brucite in fact contained 10% chrysotile, a level of contamination that could well have been responsible for the pathological changes found in both inhalation and intraperitoneal injection studies. The greatest care should be exercised by industry in handling tremolite or materials contaminated with it.

Air Pollutants, Occupational↗
PubMed1985

Kinetics of deposition and clearance of inhaled mineral dusts during chronic exposure.

New inhalation studies have been carried out with rats exposed to UICC (Union International Contre le Cancer) amosite asbestos, with the main aim of further elucidating the factors the influence the accumulation of dust in the lung during prolonged chronic exposure. The results show that, for exposure times beyond a few weeks, the lung burden rises linearly and does not level off as predicted by simple models based on ideas taken from the 1966 report of the Task Group on Lung Dynamics. Furthermore, the lung burden is found to scale directly in proportion to the exposure concentration in a way that seems to contradict the overload hypothesis stated earlier. Nevertheless, the general pattern exhibited by our results for asbestos is markedly similar to that found elsewhere for rats inhaling diesel fume, leading to the suggestion that it is general (and not specific to fibrous dust); and the hypothesis that, whereas overload of clearance can take place at high lung burdens after exposure has ceased, it is cancelled by the sustained stimulus to clearance mechanisms provided by the continuous challenge of chronic exposure. The linearity of the increase in lung burden is explained in terms of a kinetic model involving sequestration of some inhaled material to parts of the lung where it is difficult to clear. The particular sequestration model favoured is one where, the longer a particle remains in the lung without being cleared, the more likely it will be sequestrated (and therefore less likely cleared). It is believed that such ideas may eventually be useful in forming exposure-dose relations for epidemiology.

Animals↗
PubMed1983

An overload hypothesis for pulmonary clearance of UICC amosite fibres inhaled by rats.

Two types of experiments were carried out to examine the effects of deposition and clearance on the accumulation in the lungs of rats of inhaled fibres of UICC amosite. In the first experiment the mass lung burdens of the dust in question were measured as a function of the time at which animals were killed after the cessation of the six week exposure period, and in the second the masses were measured for rats removed from exposure and killed at intervals during the exposure period itself. The experimental conditions were chosen to complement those of earlier work. Taken together with the results of that earlier work, the new results provide the basis for a simple mathematical model of the kinetics of deposition and clearance which appears to account for the major observed trends. Most significantly, there is strong evidence for an overload of clearance at high lung burdens (exceeding about 1500 micrograms/rat), in which a breakdown occurs of the intermediate rate clearance mechanisms (time constants of the order of 12 days). This hypothesis is supported for inhaled asbestos dust, quartz dust, and diesel fume by results obtained elsewhere. Biological explanations for the clearance overload hypothesis are at present speculative, involving discussion of the role of the macrophage in pulmonary clearance. It is believed that the clearance overload hypothesis could have possible consequences for people occupationally exposed to airborne dusts.

Animals↗
PubMed1976

Studies of human diploid fibroblast growth. I. Responses of normal and hypopituitary cells to fibroblast growth factor, insulin, and serum.

We have assayed the growth stimulating activity of bovine insulin, fibroblast growth factor (FGF), and fetal bovine serum (FBS) in diploid human fibroblasts from normal and idiopathic hypopituitary donors. All three factors stimulated DNA synthesis in cells arrested by serum starvation. FGF was active at concentrations as low as 5 ng/ml with maximum effect at 100 ng/ml. FGF stimualted DNA synthesis at lower concentrations than did insulin and also produced a greater maximum response. Only serum was capable of supporting cell division and growth, but FGF accellerated this growth rate when it was added to serum-containing medium. Hydrocortisone, actinomycin D, and cycloheximide inhibit FGF stimulation. There was no significant difference between fibroblasts from normal and hypopituitary donors.

Animals↗
PubMed1975

Pituitary fibroblast growth factor as a stimulator of growth in cultured rabbit articular chondrocytes.

Growth promoting activity for rabbit chondrocytes has been described as a contaminant of partially pruified TSH and LH prepared from bovine and ovine pituitaries. We have investigated fibroblast frowth factor (FGF), a small growth promoting peptide isolated from bovine pituitary tissue, in a rabbit chondrocyte system. The results suggest to us that FGF is the factor or one of the factors responsible for chondrocyte growth stimulating activity previously described in the pituitary hormone preparations. DNA synthesis in these cells is stimulated by FGF at final medium concentrations of 10(-9) g/ml. Bovine NIH-LH is not stimulatory below concentrations of 10(-7) g/ml. FGF also stimulates cell growth in the presence of 10% fetal bovine serum. Dexamethasone, at concentrations of 10(-5) to 10(-9) g/ml exerts a synergistic effect with FGF on both DNA synthesis and cell growth. Over a concentration range of 10(-6) to 10(-9) g/ml, FGF does not stimulate synthesis of sulfated mucopolysaccharides.

Animals↗
PubMed1972

Physical, chemical and biological characteristics of two bovine enterovirus plaque variants.

Large plaque (4LP) and small plaque (4SP) variants were derived from a parent bovine virus strain by serial plaque passage. Both 4LP and 4SP were resistant to chloroform and stabilized at 50 degrees C for one hour by 1.0 M magnesium chloride. Both 4LP and 4SP had buoyant densities in cesium chloride of 1.36 gm/ml. Antigenically, 4LP and 4SP were reciprocally cross neutralizable. The nucleic acid of 4LP was shown to be ribonucleic acid (RNA) by resistance of its infectivity to deoxynuclease (DNase) but not ribonuclease (RNase) and by increased incorporation of [(3)H]-uridine into cytoplasmic RNA in cells of virus infected cultures. In growth characteristics, both 4LP and 4SP had maximum adsorption times of 75 to 90 minutes but 4LP had more rapid replication and release rates and yielded nearly twice as many infectious units per cell as 4SP. The differences in growth properties correlated directly with the differential in plaque diameter which was 40-50%.

Animals↗