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Biomedical subjects

A H Rose

Publications and source records attributed to A H Rose.

At least 37 records · Page 2Linked to original sources
PubMed1988

Increased pulmonary gamma interferon production in asbestosis.

In order to determine if disordered cellular immune processes are present in the lungs of persons with asbestosis, we performed bronchoalveolar lavage (BAL) on 26 patients with either crocidolite- or chrysotile-induced pulmonary asbestosis and measured the spontaneous release of gamma interferon (IFN gamma), a marker of increased cellular immune activity. For comparison, 18 control subjects and 7 patients with active pulmonary sarcoidosis were also studied. Recovered BAL cells were cultured for 24 h (5 x 10(6)/ml), and the supernatant was assayed for interferon by determining inhibition of cytopathic effect on encephalomyocarditis virus-induced lysis of WISH cells and characterized by monoclonal anti-IFN gamma antibody inhibition. Nine (35%) patients with asbestosis released increased amounts of IFN gamma, up to 320 units/ml, the levels seen in the sarcoidosis patients. All control subjects released less than or equal to 10 units/ml. All interferon released was IFN gamma. In asbestosis patients, IFN gamma production was not related to a history of cigarette smoking, there was no significant difference in the ratio of helper/inducer (Leu-3) to suppressor/cytotoxic (Leu-2) cells in IFN gamma producers compared to non-IFN gamma producers (p greater than 0.05), and IFN gamma production correlated significantly with serum IgG levels (p less than 0.001) but not with the levels of IgM, IgA, antinuclear factor, or rheumatoid factor. These data suggest that active cellular immune processes are present in the lungs of a proportion of patients with asbestosis.

Asbestosis↗
PubMed1988

Neutrophil chemotactic factor release and neutrophil alveolitis in asbestos-exposed individuals.

Alveolar neutrophil accumulation occurs in asbestosis. To evaluate a possible role for release of neutrophil chemotactic factor (NCF) in the pathogenesis of asbestosis, spontaneous NCF release from alveolar macrophages obtained by bronchoalveolar lavage (BAL) in eight individuals with asbestosis, 13 asbestos-exposed individuals without asbestosis, and five control subjects has been studied. Alveolar macrophages were incubated in medium (four hours; 37 degrees C), and neutrophil responses to the supernatants were assayed in a microchemotaxis chamber. Alveolar macrophages from subjects with asbestosis released more NCF (97 +/- 19 neutrophils per high-power field [N/HPF]) than controls (3 +/- 1 N/HPF; p less than 0.01). Alveolar macrophages from individuals with asbestos exposure and increased BAL neutrophil proportions (n = 7) released more NCF (93 +/- 24 N/HPF) than individuals with asbestos exposure and normal BAL neutrophil proportions (n = 6; 11 +/- 6 N/HPF; p less than 0.02). The results show that spontaneous NCF release occurs in asbestosis and that NCF release is associated with neutrophil alveolitis in asbestos-exposed individuals without asbestosis, suggesting a pathogenic role for NCF in mediating this neutrophil alveolitis. The results of the study also suggest that the presence of crackles is a better predictor of the presence of neutrophil alveolitis than is an abnormal chest x-ray film.

Asbestos↗
PubMed1987

Effect of ethanol on activity of the plasma-membrane ATPase in, and accumulation of glycine by, Saccharomyces cerevisiae.

The pH optimum of the ATPase activity in plasma membranes from Saccharomyces cerevisiae NCYC 431 from 8 h cultures was around 6.5 and that in membranes from organisms from 16 h cultures near 6.0. The Km[ATP] of the enzyme was virtually unaffected by the age of the culture from which organisms were harvested, although the Vmax of the enzyme in membranes from organisms from 8 h cultures was higher than that for organisms from 16 h cultures. Ethanol non-competitively inhibited ATPase activity in membranes, although the inhibition constant for the enzyme from organisms from 8 h cultures was lower than that from organisms from 16 h cultures. Glycine accumulation by the general amino acid permease was non-competitively inhibited by ethanol. Inhibition constants were virtually the same for glycine uptake by deenergized organisms from 8 h and 16 h cultures, but under energized conditions the value was greater for organisms from 16 h rather than 8 h cultures. The data indicate that inhibition of plasma-membrane ATPase activity by ethanol could account, at least in part, for inhibition of glycine accumulation by ethanol.

Adenosine Triphosphatases↗
PubMed1987

Production of long-chain alcohols by yeasts.

Fourteen yeast strains from six genera were analysed for the presence of long-chain alcohols. Six strains from three genera contained long-chain alcohols, highest levels being found in Candida albicans. The alcohols were identified and determined by TLC, GLC and GLC-MS. The major long-chain alcohols synthesized by these organisms were saturated, primary alcohols with C14, C16 or C18 chain length. Unsaturated long-chain alcohols were not detected. In all strains that produced long-chain alcohols, the relative proportions were C16 greater than C18 greater than C14. Long-chain alcohol contents were higher in organisms from anaerobically, as compared with aerobically, grown cultures reaching about 650 micrograms (g dry wt organisms)-1 in stationary-phase cultures of C. albicans. In cultures of C. albicans, synthesis of long-chain alcohols occurred only after the end of exponential growth. The alcohols were predominantly present as free alcohols. The fatty-acyl chain-length profile of the triacylglycerol and to a lesser extent the sterol/wax ester fractions from C. albicans reflected that of the long-chain alcohols produced by this yeast.

Alcohols↗
PubMed1987

Comparison of bronchoalveolar lavage helper/suppressor T-cell ratios in sarcoidosis versus other interstitial lung diseases.

In order to compare the frequency of elevated lymphocyte proportions and elevated Leu3/Leu2 (helper/inducer to suppressor/cytotoxic) ratios in sarcoidosis with those in clinically similar interstitial lung diseases (ILDs), bronchoalveolar lavage (BAL) lymphocyte proportions and Leu3/Leu2 ratios were determined for 20 patients with sarcoidosis and 30 patients with other (non-sarcoidosis) ILDs [cryptogenic fibrosing alveolitis (seven), lung connective tissue disease (seven), extrinsic allergic alveolitis (four), lymphoproliferative disease (two), and asbestosis (ten)], as well as in eight control subjects. BAL lymphocyte proportions were elevated above control values in 19 (95%) patients with pulmonary sarcoidosis (mean value 36 +/- 3%) but also in 12 (39%) patients with non-sarcoidosis ILDs (mean value 17 +/- 4%). Leu3/Leu2 ratios were over 2.5 in 15 (75%) of the sarcoidosis patients (mean ratio 4.4 +/- 1). In all control subjects, however, and in all but one of the non-sarcoidosis groups, Leu3/Leu2 ratios were below 2.5 (p less than 0.001 for each compared to sarcoidosis patients). Helper/suppressor ratios over 2.5 are found in the majority of our sarcoidosis patients and, unlike raised lymphocyte proportions alone, are not commonly seen in other ILDs, suggesting that evaluation of BAL helper/suppressor cell ratios may be of value in the investigation of patients with ILD.

Adult↗
PubMed1986

Alveolitis of pulmonary asbestosis. Bronchoalveolar lavage studies in crocidolite- and chrysotile-exposed individuals.

Bronchoalveolar lavage (BAL) findings in 27 individuals with crocidolite- or chrysotile-induced asbestosis were compared to BAL findings in 29 unexposed control subjects. Alveolitis, defined as an increase in the proportions and/or absolute numbers of inflammatory cells present in BAL fluid compared to values in control subjects, was present in 26 (96 percent) subjects with asbestosis. Most exhibited a neutrophil-eosinophil alveolitis, with neutrophil proportions increased to 7.4 +/- 0.7 percent and eosinophil proportions increased to 2.2 +/- 0.4 percent, compared to 2 +/- 0.5 percent and 0.4 +/- 0.01 percent, respectively, in control subjects (p less than 0.01 for both neutrophils and eosinophils). An increase in the total number of neutrophils and eosinophils per ml of lavage fluid was also seen (neutrophils 23 +/- 5 and eosinophils 13 +/- 4 per ml; p less than 0.05 compared to control subjects). Severity of the alveolitis, defined by the neutrophil or eosinophil proportions, was independent of a history of exposure to cigarette smoke. The pattern and severity of alveolitis in crocidolite- and chrysotile-induced asbestosis were similar. There was a significant correlation between duration of exposure to asbestos and neutrophil proportions (p less than 0.01). No significant difference in the severity of the alveolitis was observed between individuals with radiologic and physiologic evidence of asbestosis compared to those with asbestos exposure and crackles alone, suggesting that, in asbestosis as in other chronic interstitial lung diseases, radiologic and physiologic parameters do not reflect the severity of the alveolitis. This study demonstrates that a neutrophil-eosinophil alveolitis is present in individuals with crocidolite- and chrysotile-induced asbestosis, that this alveolitis is independent of cigarette smoking, and that the severity of the BAL changes is not reflected in radiologic and physiologic changes.

Asbestos↗
PubMed1985

Plasma-membrane phospholipid unsaturation affects expression of the general amino-acid permease in Saccharomyces cerevisiae Y185.

Saccharomyces cerevisiae Y185, enriched in linoleyl residues and incubated for up to 4 h in derepression buffer, more rapidly acquired general amino-acid permease (GAP) activity, as measured by the rate of accumulation of L-alanine, compared with organisms enriched in oleyl residues. A GAP-less mutant incubated under the same conditions did not acquire further L-alanine-accumulating ability, irrespective of the nature of the fatty-acyl enrichment. During derepression, KT values for the GAP were virtually identical irrespective of the fatty-acyl enrichment, but Vmax values were greater for linoleyl residue-enriched organisms, particularly after 1 h in derepression buffer. During incubation in derepression buffer, organisms with either fatty-acyl enrichment did not differ in the size of the amino-N pool, the concentration of L-alanine in that pool, rates of protein synthesis and glucose fermentation, or rate and extent of incorporation of label from H2 32PO-4. Under conditions used to measure rates of L-alanine accumulation, organisms with either enrichment showed no evidence of metabolism of accumulated L-alanine.

Alanine↗
PubMed1983

IgE responses of malnourished mice: immunogenic and tolerogenic effects of low-grade antigenic stimulation.

Mice maintained on protein-restricted diets after weaning manifested normal IgE (and IgG) responses following intraperitoneal immunization under conditions of maximal antigenic stimulation, i.e., antigen adsorbed to adjuvant. However, antigenic challenge at levels closer to the stimulation threshold, employing soluble antigen alone, revealed marked differences between the immune competence of normal and malnourished animals. Diminished IgE responsiveness to soluble antigen in the malnourished mice was accompanied by enhanced susceptibility to the induction of antigen-specific tolerance associated with the appearance of suppressor T cells in the spleen. It is argued that enhanced susceptibility to suppressor T-cell induction under conditions of minimal antigenic stimulation may underlie the diminished IgE responsiveness of the malnourished animals.

Administration, Intranasal↗
PubMed1982

The effect of a low protein diet on the immunogenic activity of murine peritoneal macrophages.

The activity of resident and exudate peritoneal macrophages from mice maintained on a low protein diet (4% casein initiated at weaning) was assessed in a variety of assay systems which examined aspects of macrophage 'immunogenic' function in vivo and in vitro. Antigen-pulsed macrophages from malnourished mice triggered secondary IgE and IgG responses following intraperitoneal inoculation into pre-immunized syngeneic recipients. Similarly, intraperitoneal transfer of low numbers of these cells successfully primed immunologically naive syngeneic mice; in both cases, the activity of macrophages from malnourished mice could not be distinguished from these derived from normal animals. Examination of uptake and breakdown of radio-labelled antigen revealed normal rates of phagocytosis, and a brief lag in the early phase of degradation, relative to control macrophages. Antigen-pulsed macrophages from malnourished mice were severely impaired in their capacity to trigger the proliferation of antigen-primed T cells in vitro.

Animals↗
PubMed1981

Induction of adjuvant-independent IgE responses in inbred mice: primary, secondary, and persistent IgE responses to ovalbumin and ovomucoid.

Immunization of a number of inbred mouse strains intraperitoneally with low levels (1-100 micrograms) of ovalbumin (OA) or ovomucoid (OM) in the absence of adjuvant, revealed marked strain differences in IgE responsiveness. High-OA-responder strains such as Balb/c exhibited PCA titre up to 256 in the primary response, and up to 1,280 in the secondary, while non-responders such as SJL and NZB remained PCA negative; similar variations were found in the response of the strains to OM. Repeated immunization of high-OA-responder mice with low doses of antigen without adjuvant elicited anamnestic second and tertiary HA antibody responses. In contrast, IgE responses exhibited anamnestic secondary responses, but were not further boosted by tertiary stimulation. Instead, a 'persistent' high IgE response of the type previously associated with the use of specialized adjuvants, developed in these mice. Fractionation of the OA antigen by gel filtration yielded molecular species (dimers pentamers) of considerably greater IgE-immunogenicity than either monomeric OA or very highly aggregated forms. Immunization of high-OA-responder mice with the former permitted lowering of the threshold for induction of adjuvant-independent primary OA-IgE responses to a single 1.0 microgram dose, and the threshold for priming to 0.1 microgram.

Animals↗
PubMed1980

Effect of a low protein diet on IgE antibody responses in Balb/c mice.

Mice maintained on a low protein diet (4% casein initiated at weaning) produced IgE antibody responses to both ovalbumin and Ascaris body fluid proteins. The titres in young mice were comparable to those of mice maintained on a normal (20% protein) diet particularly at high doses of immunogen. However, following immunization with low doses of immunogen the initiation of antibody response in malnourished mice was delayed and the levels finally obtained were significantly suppressed below normal levels. This effect was more apparent in animals maintained for prolonged periods on diet. Possible mechanisms for this suppression are presented.

Animals↗
PubMed1979

Inhibitory effect of ethanol on growth and solute accumulation by Saccharomyces cerevisiae as affected by plasma-membrane lipid composition.

Incorporation of ethanol (1.0 or 1.25 M) into exponential-phase cultures of Saccharomyces cerevisiae NCYC 366 growing anaerobically in a medium supplemented with ergosterol and an unsaturated fatty acid caused a retardation in growth rat, which was greater when the medium contained oleic rather than linoleic acid. Ethanol incorporation led to an immediate drop in growth rate, and ethanol-containing cultures grew at the slower rate for at least 10 h. Incorporation of ethanol (0.5 M) into buffered (pH 4.5) cell suspensions containing D-[6-3H] glucose, D-[1-14C] glucosamine, L-[U-14C] lysine or arginine, or KH232PO4 lowered the rate of solute accumulation by cells. Rates of accumulation of glucose, lysine and arginine were retarded to a greater extent when cells had been grown in the presence of oleic rather than linoleic acid. This difference was not observed with accumulation of phosphate. Ethanol was extracted from exponential-phase cells by four different methods. Cells grown in the presence of linoleic acid contained a slightly, but consistently, lower concentration of ethanol than cells grown in oleic acid-containing medium. The ethanol concentration in cells was 5-7 times greater than that in the cell-free medium.

Anaerobiosis↗
PubMed1979

Scanning electron microscope study of Saccharomyces cerevisiae spheroplast formation.

A suspension of Saccharomyces cerevisiae NCY366 in buffered 1.2 M sorbitol containing Zymolyase-5000 (a beta-glucanase-containing preparation/showed maximum osmotic sensitivity after 30 min of incubation at 30 degrees C. A scanning electron microscope study of spheroplast formation, using a very high resolution (4-nm) machine, revealed several new morphological features. The surface of the plug in bud scars on intact cells appeared warty. The wall, which assumed a beady appearance as digestion proceded, ultimately sloughed off to reveal the furrowed surface of the plasma membrane. Bud scars were resistant to digestion and. as incubation proceeded, they became surrounded by an outer annulus, which may be the seconary septum. Wall material was completely removed from the majority of cells only after 60 min of digestion. The surface of spheroplasts was studded with particles, about 25 to 30 nm in diameter. Many spheroplasts had a single large indentation, which may be in that part of the plasma membrane originally underlying the birth scar.

Cell Membrane↗
PubMed1979

Changes in electrophoretic mobility and lytic enzyme activity associated with development of flocculating ability in Saccharomyces cerevisiae.

Cells from stationary-phase cultures of two strains of Saccharomyces cerevisiae (3 and 20) failed to flocculate when grown in a complex or a chemically defined medium, while those of two other strains (11 and 13) flocculated when grown in either medium. Strain 30 flocculated when grown in complex but not defined medium and harvested from stationary-phase cultures. pH-electrophoretic mobility measurements on all five strains showed that mobility attributable to carboxyl groups usually increased as cultures progressed from the exponential to the stationary phase, while that caused by phosphate groups tended to decline. Acquisition of flocculating ability was accompanied in strains 11 and 30 by a slight increase in amidase activity, and greater increases compared with nonflocculent populations in activities of leucine aminopeptidase. alpha-mannosidase, and proteinase C. Activities of proteinases A and B showed no correlation with acquisition of flocculating ability.

Amidohydrolases↗
PubMed1978

Plasma-membrane lipid composition and ethanol tolerance in Saccharomyces cerevisiae.

Populations of cells suspended anaerobically in buffered (pH 4.5) M ethanol remained viable to a greater extent when their plasma membranes were enriched in linoleyl rather than oleyl residues irrespective of the nature of the sterol enrichment. However, populations with membranes enriched in ergosterol or stigmasterol and linoleyl residues were more resistant to ethanol than populations enriched in campesterol or cholesterol and linoleyl residues. Populations enriched in ergosterol and cetoleic acid lost viability at about the same rate as those enriched in oleyl residues, while populations grown in the presence of this sterol and palmitoleic acid were more resistant to ethanol. Suspending cells in buffered ethanol for up to 24 h did not lower the ethanol concentration.

Anaerobiosis↗