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M J Armstrong

Publications and source records attributed to M J Armstrong.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effect of sampling time on chromosome aberration yield for 7 chemicals in Chinese hamster ovary cells.

Choice of harvest time is one of the most important variables in the assessment of whether a compound is clastogenic and in establishing a dose relation. We examined the effects of sampling time on aberration yield for 7 diverse chemicals in CHO-WBL cells by harvesting at intervals from 9 to 30 h after treatment for 3 h with or without S9 metabolic activation. We observed both the percentage of aberrant cells and the total number of aberrations. Our data suggest that for most compounds a single harvest time approximately 17-21 h after the beginning of a 3-h treatment is optimal for aberration detection in CHO cells. Maximal aberration yields were observed for 2,4-diaminotoluene, 2,6-diaminotoluene and cytosine beta-D-arabinofuranoside from 17 to 21 h, eugenol from 15 to 21 h, cadmium sulfate from 15 to 24 h and 2-aminobiphenyl, from 17 to 24 h. For adriamycin at 1 microM, the % aberrant cells remained elevated throughout the period from 9 to 29 h, while small increases at 0.1 microM ADR were found only at 13 and at 25 h. For most chemicals the maximal aberration yield occurred at a different time for each concentration tested. However, the use of 3 or more closely spaced concentrations, carefully selected to yield up to 50% toxicity, allowed detection of a positive response at a single harvest time for all 7 chemicals.

Aminobiphenyl Compounds↗
PubMed1992

A quantitative assessment of the cytotoxicity associated with chromosomal aberration detection in Chinese hamster ovary cells.

Regulatory guidelines suggest testing chemicals up to cytotoxic doses in chromosomal-aberration assays. To investigate the utility and limitations of various cytotoxicity indicators we used Chinese hamster ovary (CHO) cells to test 8 chemicals with differing ratios of cytotoxicity to clastogenicity. We measured immediate or delayed cell killing and growth inhibition (ATP levels, cell counts, colony-forming efficiency, CFE) and cell-cycle perturbations (mitotic index, MI; average generation time, AGT). Aberrations (abs) were scored 10 and 24 h from the beginning of the 3-h treatment. All 8 compounds induced abs at concentrations that reduced cell growth at 24 h by 50% or less. Concentrations of each chemical which induced at least 15% cells with abs, gave little loss of CFE (0-20%) for mitomycin C, adriamycin, cadmium sulfate and 2,6-diaminotoluene in contrast to the marked loss of CFE (70-80%) for eugenol (EUG), 2-aminobiphenyl and 8-hydroxyquinoline (8-HQ). 2,4-Diaminotoluene (2,4-DAT) was intermediate. Higher aberration yields were found at 24 h than at 10 h, even when minimal cell-cycle delay was detected by AGT estimates from BrdUrd-labeled cells. Cells with multiple abs were seen at 24 but not at 10 h, and often confirmed clastogenicity when there was only a weak increase in the percentage of cells with aberrations. Total ATP per culture did not always correlate with cell number, especially at later times after treatment. This is likely due to metabolic perturbations or altered cell biomass that are known to affect cell ATP content. MI suppression often did not correlate with AGT, e.g., only small increases in AGT were seen for 8-HQ, 2,4-DAT and EUG despite severe mitotic suppression at 10 h. By 24 h the MI for all chemicals had recovered, sometimes exceeding control levels. Marked mitotic accumulation was seen at 10 h for 2,4-DAT, indicating cell synchrony. Thus, the MI has limited value for dose selection. In conclusion, even weakly active chemicals were detected at a single time without exceeding a 50% growth reduction at 24 h.

Aminobiphenyl Compounds↗
PubMed1992

Expression of phosphatidylinositol-dependent phospholipase C sensitive Qa-2 antigen is increased on peripheral blood lymphocytes of aging mice.

Qa-2 antigen, a nonclassical MHC antigen, is one of a group of cell surface antigens that may be anchored to the cell surface by a glycophosphatidylinositol (GPI) linkage rather than, as is the case with the classical MHC antigens, K, D, and L, by a transmembrane linkage. Recent studies have shown that T cells may be activated through the cross-linking of GPI anchored Qa-2 antigens by anti-Qa-2 antiserum. The Qa-2 antigens involved in signal transduction in activated T cells are sensitive to lipolytic cleavage by phosphatidylinositol-dependent-phospholipase C (PI-PLC). Since T cell function is known to decline with age, a study was undertaken to determine whether the relative amount of lipase sensitive Qa-2 antigen changes with age. Ficoll- Hypaque purified peripheral blood lymphocytes were obtained from C57BL/6 and A strain mice from 6-30 months of age. The cells were incubated with or without phosphatidylinositol- dependent-phospholipase C followed by incubation with anti-Qa-2 monoclonal antibodies and a fluorescein labeled second antibody. Analysis on a FACScan flow cytometer demonstrated that the A strain mice had a single population of Qa-2 positive lymphocytes which increased in lipase sensitivity with age. The C57BL/6 strain mice of all ages had two populations of Qa-2 positive cells, one staining with high fluorescence intensity (high antigen density) and the other with low fluorescence intensity (low antigen density). The proportion of cells found in the high density peak increased markedly with age, suggesting on overall increase in Qa-2 expression. In young animals, only the high density peak was sensitive to PI-PLC treatment. In older animals, the cells originally appearing in the high density population shifted to the low density population after treatment with PI-PLC, suggesting that there must be both lipase sensitive and lipase insensitive forms of Qa-2 present on lymphocytes in these aging C57BL/6 mice. Overall, these data suggest that the proportion of lymphocytes expressing lipase sensitive Qa-2 is increased on lymphocytes of old mice. Since a role for lipase sensitive GPI-linked Qa-2-antigen has recently been postulated in T cell activation, it is possible that the increased lipase sensitive Qa-2 antigen may play a role in age-related changes in T cell function.

Aging↗
PubMed1991

Expression of a negative regulator of human erythropoiesis by fluidized lymphocyte plasma membranes.

Regulation of hematopoiesis by paracrine molecules occurs in vitro. In some cases, hematopoietic paracrine factors have been localized to the plasma membrane of accessory cells. We have purified a unique integral membrane glycoprotein from normal human B cells that functions in vitro as a paracrine factor whose activity is directed toward erythroid progenitor cells. This factor is also spontaneously exfoliated from the cell surface as a component of extracellular vesicles. Analysis of the lipid and protein compositions and membrane lipid order of these extracellular vesicles reveals them to be biochemically distinct and more fluid than their parent membranes. Evidence in nonhematopoietic culture systems indicates that cell membrane function may be altered by modifying membrane fluidity. In an effort to accelerate growth factor release, plasma membranes of B cells were fluidized by incubation with an emulsion of Liposin II, phosphatidylcholine, and phosphatidylethanolamine. Fluidity assessed by steady-state fluorescence polarization was reduced in lipid-treated cells. Exfoliation was 3-4-fold higher from lipid-treated cells relative to untreated cells. Unexpectedly, a negative signal for burst-forming unit-erythroid (BFU-E) proliferation was expressed in membranes, in shed extracellular vesicles, and in supernatants of medium conditioned by the fluidized cells. Purification of the inhibitor is under way. The data are consistent with the hypothesis that accessory cell plasma membranes may positively or negatively regulate erythroid differentiation, depending upon the exchange of cholesterol and phospholipids between plasma membrane and ambient lipid pools.

B-Lymphocytes↗
PubMed1991

New Zealand Maori women's health: status and self-help action in the 1980s.

The indigenous Maori population of New Zealand has experienced improvements in health in recent decades but vis-à-vis the non-Maori segment of the population, Maori, and Maori women in particular, continue to be disadvantaged. The situation became the focus of attention during the 1980s. Among efforts to improve it, a broad-based self-help campaign initiated by Maori leaders, organizations and health professionals emerged as important. This paper documents the current status of Maori women's health and examines health-related self-help activities on the part of the Maori Women's Welfare League, the leading Maori women's organization. The League has taken a leading role in the self-help campaign, declared a Decade of Health for 1985-1995, and adopted a program of action that could help to significantly improve the status of Maori health.

Age Factors↗
PubMed1990

Early amniocentesis: experience of 222 consecutive patients, 1987-1988.

Early amniocentesis from 9 to 14 weeks' gestation provides a safe and accurate method of prenatal diagnosis of cytogenetic and biochemical disorders. There was a 100 per cent success rate in culturing the amniotic cells from 222 samples obtained between 9 and 14 weeks' gestation. Follow-up of the patients to delivery revealed an abortion rate of 1.4 per cent. Among the 207 live- and stillborn infants, only one had a congenital abnormality (bilateral talipes equino-varus) and no infant had respiratory distress syndrome or pneumonia. Eleven pregnancies were terminated following the detection of a chromosomal, biochemical, or congenital abnormality (5.0 per cent). However, before the procedure of early amniocentesis becomes routine clinical practice, it requires appraisal by a randomized clinical trial.

Amniocentesis↗
PubMed1990

Characterization of biologically active, platelet-derived growth factor-like molecules produced by murine erythroid cells in vitro and in vivo.

Platelet-derived growth factor (PDGF) is an important serum regulator of erythropoiesis in vitro. We have now obtained evidence suggesting that PDGF-like molecules may also modulate erythropoiesis in vivo. Western blot analysis of cytoplasmic extracts from Rauscher murine erythroleukemia cells and phenylhydrazine-treated mouse splenic erythroid cells revealed the presence of several PDGF-like proteins. The presence of PDGF-like proteins in the cytoplasm of these two erythroid cell types was confirmed by immunohistochemical staining. Using a serum-free biologic assay, PDGF-like biological activity was found in cell lysates and conditioned medium of both Rauscher cells and phenylhydrazine-treated mouse erythroid cells. Subcellular localization experiments revealed the biological activity to be concentrated in the cytosolic fraction. Using a series of antibodies to hematopoietic growth factors we demonstrated that PDGF-like biological activity was specifically immunoprecipitated by both monoclonal and polyclonal anti-human PDGF antibodies but not by antibodies to burst-promoting activity, granulocyte-macrophage colony-stimulating factor, IL-3, or erythropoietin. Taken together, the data are consistent with the hypothesis that PDGF-like molecules play a role in the regulation of mammalian erythropoiesis in vivo.

Animals↗
PubMed1989

Effects of H-2 haplotype and gender on the lifespan of A and C57BL/6 mice and their F1, F2, and backcross offspring.

The effects of H-2 type and gender on the lifespan of A and C57BL/6 mice and their F1, F2, and backcross offspring were studied. The proportion of mice remaining alive, percent survivors, was calculated at monthly intervals for each mating group. Statistical analyses of these survival data showed that, in agreement with studies from other laboratories, C57BL/6 (H-2b) mice lived significantly longer than A (H-2a) mice. When the survival curves for A and C57BL/6 backcross and F2 offspring were analyzed to test for the presence of an H-2 effect on mouse lifespan, no statistically significant association was detected, although a trend toward increased 10th decile survivorship among female H-2a mice was noted. The mice used in this study were also evaluated for the presence of an effect of gender on lifespan. Female mice of the A strain, and F1, F2, and backcross groups, but not the C57BL/6 mice, exhibited significantly longer lifespans when compared with their male counterparts. Thus these data show a significant gender effect, but only a trend towards an H-2 effect, on the lifespan of A and C57BL/6 mice and their F1, F2, and backcross offspring.

Animals↗
PubMed1988

Structurally distinct plasma membrane regions give rise to extracellular membrane vesicles in normal and transformed lymphocytes.

Shedding of extracellular membranes from the cell surface may be one of the means through which cells communicate with one another. In an attempt to elucidate whether cell surface exfoliation is a directed or random process, we investigated the membrane lipid and protein composition and membrane lipid order of shed extracellular membranes and of plasma membranes from which they arose in normal circulating lymphocytes and in the B-lymphoblastoid cell lines Raji, WI HF2 729 and the T-lymphoblastoid cell line Jurkat. Extracellular membranes derived from transformed cell lines were more rigid as assessed by steady state polarization of 1,6-diphenylhexatriene (DPH) and were highly enriched in cholesterol when compared with the corresponding plasma membrane. The extracellular membranes from normal lymphocytes, on the other hand, were more fluid and contained more polyunsaturated acyl chains than did the plasma membranes from these cells. Our results suggest that extracellular membranes are shed from specialized regions of the lymphocyte plasma membrane and that membrane exfoliation is likely to be a directed event.

Animals↗
PubMed1987

Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: evaluations of 108 chemicals.

Results from the testing of 108 coded chemicals in Chinese hamster ovary (CHO) cells for the induction of chromosome aberrations and sister chromatid exchanges (SCEs) are presented. All chemicals were tested with and without exogenous metabolic activation, using protocols designed to allow testing up to toxic doses. Cell harvest times could also be extended if chemical-induced cell cycle delay was seen. Chromosome aberrations were induced by 43 of the chemicals, and 66 induced SCEs; 37 of the chemicals were positive for both endpoints.

Animals↗
PubMed1987

Effects of high osmotic strength on chromosome aberrations, sister-chromatid exchanges and DNA strand breaks, and the relation to toxicity.

Substantial increases in chromosome aberrations were induced in Chinese hamster ovary cells by medium made hyperosmotic with NaCl, KCl, sucrose, sorbitol or dimethyl methylphosphonate. The increases were associated with cytotoxicity but occurred in the range (e.g., 70% survival) commonly included in in vitro tests for 'genotoxicity'. The relation between increased osmotic pressure and chromosome aberrations is compound-dependent, e.g., some compounds may have a direct effect in addition to an effect mediated by osmotic pressure/ionic strength. Also, glycerol at high osmolality was not toxic and did not induce aberrations, probably because rapid equilibration across the cell membrane precluded severe osmotic stress to the cells. Weak increases in DNA single-strand breaks (NaCl and KCl) and double-strand breaks (NaCl) were also detectable, at higher concentrations and more toxic levels than those required to produce aberrations. Slight elevations in sister-chromatid exchange frequencies caused by hyperosmotic medium were found in the presence of toxicity and severe cell cycle delay. Our data on cell growth inhibition suggest that this is the result of increased incorporation of bromodeoxyuridine per cell due to decreased numbers of growing cells, although other mechanisms cannot be ruled out. The observations on chromosome aberrations demonstrate the need for keeping in vitro test conditions in the physiological range, and provide a means for investigation of indirect DNA damage.

Animals↗
PubMed1987

Relationships among cytotoxicity, lysosomal breakdown, chromosome aberrations, and DNA double-strand breaks.

Certain chemicals that are either weak or non-carcinogens had been previously shown to induce DNA single-strand breaks in rat hepatocytes, but only at cytotoxic doses. In contrast, stronger carcinogens induced DNA single-strand breaks at non-toxic doses. This report shows that the strong carcinogens and mutagens cadmium sulfate, sodium dichromate, dimethyl sulfate, and N-methyl-N'-nitro-N-nitrosoguanidine all induce DNA single-strand breaks at non-toxic concentrations, but that they also induce DNA double-strand breaks at concentrations that are closely correlated with cytotoxicity. Some weak carcinogens produced DNA single- and double-strand breaks, but only at acutely cytotoxic concentrations. We suggest that the DNA double-strand breaks result from a cell-mediated process such as release of DNAase from lysosomes or other cellular compartments, that might occur during cellular response to acutely toxic damage. Experiments with N-dodecyl imidazole (NDI), a lysosomal detergent, show that lysosomal breakdown alone is only a weak inducer of DSBs, but that lysosomal breakdown in combination with prior chemical damage produced by MNNG synergistically induces DNA DSBs in BHK cells. N-Dodecyl imidazole also induces chromosomal aberrations in CHO cells at concentrations which cause cytotoxicity, cell cycle delay, and lysosomal breakdown. These results all suggest that chemical toxicity leads to limited lysosomal breakdown that induces DNA DSBs and chromosomal aberrations. Cells that have been sublethally damaged and that can repair these damages and survive could become transformed by the DNA-damaging mechanisms associated with carcinogenesis.

Animals↗
PubMed1987

Dolichol content and isoprenolog distribution in developing rat small intestine.

We examined developmental changes in dolichol concentration and isoprenolog distribution during the postnatal development of rat small intestine. We isolated dolichols from rat small intestinal lipids and quantified the isoprenologs by high performance liquid chromatography. The concentration of intestinal dolichol was highest in the intestine of the newborn rat and lowest in intestine from 19-day-old and lactating female rats. The predominant isoprenolog at all ages examined was that with 18 isoprene units. There was a significant increase in isoprenolog 17 during the 3rd wk of postnatal development and an increase in isoprenolog 19 in the adult rat small intestine. The timing of the changes in dolichol content suggests that this might be an important control point in intestinal glycoprotein synthesis during development.

Animals↗
PubMed1987

Thermodynamic and molecular determinants of sterol solubilities in bile salt micelles.

We examined, by reverse-phase high performance liquid chromatography (HPLC), the hydrophilic-hydrophobic balance of cholesterol and 12 non-cholesterol sterols and related this property to their equilibrium micellar solubilities in sodium taurocholate and sodium glycodeoxycholate solutions. Sterols investigated exhibited structural variations in the polar function (3 alpha-OH, 3 beta-OH, 3 beta-SH), nuclear double bonds (none, delta 5, or delta 7), side chain length (C27, C28, C29) and side chain double bonds (none, delta 22, or delta 24). In general, a sterol's hydrophilic-hydrophobic balance became progressively more hydrophobic (as exemplified by increasing HPLC retention values, k') with additions of side chain methyl (C28) and ethyl (C29) groups and with 3 beta-SH substitution of the 3-OH polar function. Side chain delta 22 and especially delta 24 double bonds rendered the sterols appreciably more hydrophilic, whereas a single nuclear double bond had little influence. Sterol solubilities (24 degrees C, 0.15 M Na+) were uniformly greater in 50 mM solutions of sodium glycodeoxycholate (range 0.15 to 2.5 mM) than in equimolar solutions of the more hydrophilic bile salt, sodium taurocholate (range 0.07 to 0.67 mM). For each bile salt system, a strong inverse correlation existed between micellar solubilities of sterols and their HPLC k' values, indicating that more hydrophilic sterols had greater micellar solubilities than the more hydrophobic ones. Based upon the aqueous monomeric solubilities of cholesterol (C27) and beta-sitosterol (C29) at 24 degrees C, we derived free energy changes associated with micellar binding and found that solubilization of both sterols was more energetically favored in glycodeoxycholate solutions. Although cholesterol exhibited a higher binding affinity than beta-sitosterol in glycodeoxycholate micelles, solubilization of beta-sitosterol in taurocholate micelles was more energetically favored than cholesterol by -0.6 kcal/mol. Based upon these results we offer a thermodynamic explanation for the greater micellar solubilities of more hydrophilic sterols and suggest that the high affinity, but low capacity, of a typical phytosterol for binding to trihydroxy bile salt micelles may provide a physical-chemical basis for its inhibition of intestinal cholesterol absorption.

Animals↗
PubMed1986

Neurotensin stimulates [3H]oleic acid translocation across rat small intestine.

The effect of neurotensin (NT) on the translocation of intraluminally administered lipid across the duodenum as well as across the entire length of the small intestine was studied in the rat. In the first series of experiments, the appearance in the lymph of [3H]oleic acid instilled as a bolus into a segment of the duodenum was followed for 3 h. Infusion of NT (0.6 pmol X kg-1 X min-1) via the superior mesenteric artery resulted in a significant increase in the appearance of label in the lymph when compared with saline infusion (17.3 +/- 3.1 vs. 8.6 +/- 1.4%, P less than 0.01, respectively). In the second series of experiments, lipid was infused into the entire length of the small intestine over 4 h, and the accumulation of label in the lymph was measured. The infusion of NT (1.0 pmol X kg-1 X min-1) into the femoral vein also significantly increased the appearance of label when compared with animals infused with saline (49.0 +/- 2.0 vs. 34.2 +/- 5.2%, P less than 0.05, respectively). In this study, the specific activity of the triglyceride recovered in the lymph was higher in the rats given NT than in the controls (P less than 0.05). No significant changes in lymph flow were observed as a consequence of NT infusion. These results indicate that NT infusion into the circulation increases the translocation of oleic acid from the intestinal lumen into the lymph of rats.

Animals↗
PubMed1985

Alcohol and fatty acid stimulation of neurotensin release from rat small intestine.

We have previously reported that neurotensin (NT) is released from the small intestine and elevated in the hepatic-portal circulation in response to the perfusion of the small intestine with a micellar solution of oleic acid. In order to determine the minimum acyl chain length and whether the presence of a carboxylic acid is necessary for the stimulation of NT release, the small intestine of anesthetized rats was perfused with test solutions of fatty acids of 2-, 4-, 8-, or 18-carbons or fatty alcohols of 2-, 4-, or 8-carbons at a concentration of 1 mM prepared in 2.4 mM taurodeoxycholate in 0.9% NaCl. Blood samples, collected from the superior mesenteric vein immediately before the start of the test perfusion and at 15-min intervals thereafter, were extracted immediately and radioimmunoassayed for NT-like immunoreactivity (NTLI) with a C-terminal-directed antiserum. Perfusions of fatty acids with 4 or more carbons and alcohols of 2 or more carbons resulted in a significant elevation (P less than 0.05) in plasma levels of NTLI above the values obtained before the onset of perfusion. Perfusions with ethanol resulted in a value of 4.3 +/- 0.03 mg/dl (SEM) in blood from the superior mesenteric vein while there was no increase in ethanol levels in the peripheral circulation. Perfusion with taurodeoxycholate and 0.9% NaCl alone had no significant effect on plasma levels of the NTLI. In order to characterize the chemical nature of the elevated NTLI, plasma samples from animals perfused with test solution were collected, extracted, pooled, and subjected to HPLC. NT and its N-terminal metabolite, NT(1-8), were quantitated. NT was defined as material having the same retention time as synthetic NT standard and having comparable measurements using N- and C-terminal-directed antisera. Perfusions of fatty acids of four or more carbons and alcohols of two or more carbons resulted in a 2- to 4-fold increase of both NT and NT(1-8) levels in plasma. It is particularly interesting that perfusion with ethanol (2-carbons) causes an elevation in plasma NT, because perfusion with acetic acid (2-carbons) does not increase NTLI. The fact that perfusion of ethanol is effective in releasing intestinal NT suggests that NT may mediate some of the biological effects observed after the consumption of alcohol.

Acetates↗
PubMed1983

Salted fish and inhalants as risk factors for nasopharyngeal carcinoma in Malaysian Chinese.

We conducted a case-control study of nasopharyngeal carcinoma among Malaysian Chinese to test inhalants, salted fish consumption, and use of tobacco, alcohol, and nasal ointments as risk factors for the disease. Interviews with 100 cases and 100 controls indicated that salted fish consumption during childhood was a significant risk factor (relative risk, 3.0; p = 0.04); childhood daily consumption of this food item compared to nonconsumption carried a relative risk of 17.4 [95% confidence interval = (2.7, 111.1)]. Occupational exposure to smokes (relative risk, 6.0; p = 0.006) and to dusts (relative risk, 4.0; p less than 0.001) was also significantly associated with nasopharyngeal carcinoma. The two risk factors (consumption of salted fish and exposure to smoke and/or dust) were independent of each other. There was no association between nasopharyngeal carcinoma and tobacco, alcohol, or nasal ointments.

Administration, Intranasal↗