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Biomedical subjects

R L Hanson

Publications and source records attributed to R L Hanson.

At least 127 records · Page 7Linked to original sources

Comparison of lung burdens of inhaled particles of rats exposed during the day or night.

Inhalation studies frequently involve daytime exposures of nocturnal animals to toxicants. Such exposures may result in different respiratory tract depositions than would be obtained if rodents were exposed at night. Our study assessed the effect of night versus day exposures on lung burdens of particles inhaled by Fischer 344 rats. One group of 15 female rats was exposed to 0.3 micron volume median diameter particles of gallium oxide (Ga2O3) for 11.2 h during the day and a second group of 15 female rats was exposed to the same aerosol for 11.2 h at night. Gallium in the lungs at the end of exposure was measured by electrothermal atomic absorption spectrometry. Rats exposed during the night had significantly (p less than 0.05) higher lung burdens than day-exposed rats when burdens were expressed as either microgram Ga2O3/lung (mean +/- SD = 896 +/- 175 versus 698 +/- 150) or microgram Ga2O3/g lung (mean +/- SD = 683 +/- 134 versus 465 +/- 103). The greater amount of material in lungs of rats exposed at night probably reflected increased ventilation accompanying nocturnal activity.

Aerosols↗

Stimulation of insulin secretion from isolated rat islets by SaRI 59-801.

Oral administration of SaRI 59-801 (DL-alpha-[dimethylaminomethyl]-2-[3-ethyl-5-methyl-4-isoxazolyl]-1H- indole-3-methanol) has been reported to decrease blood glucose in several species and to elevate plasma insulin in rats and mice. In studies with isolated rat pancreatic islets incubated 1 h with 3 mM glucose, 0.05 mM 59-801 produced a significant increase in insulin secretion, and 0.3 mM produced maximum release. 59-801 (0.3 mM) stimulated insulin release 4-5-fold from islets incubated with 0, 3, or 5 mM glucose but had little effect on the high rates of release obtained at 10 or 20 mM glucose. Ten millimolar mannoheptulose, which inhibits phosphorylation of glucose and blocks glucose-stimulated insulin release, had little effect on the stimulation of insulin release by 0.3 mM 59-801 from islets incubated with 3 mM glucose. Stimulation of insulin release in the absence of glucose or in the presence of 3 mM glucose plus 10 mM mannoheptulose suggests that glucose metabolism is not required for the action of 59-801. The rate of conversion of 5 mM [5(-3)H]-glucose to 3H2O by islets, a measure of the rate of glycolysis, was not affected by 59-801. The potency, dependency on glucose concentration, lack of inhibition by mannoheptulose, and lack of effect on glycolysis of 59-801 were similar to that of tolbutamide. However, proinsulin synthesis by islets incubated with 5.55 mM glucose was not affected by 0.5 mM 59-801, but was inhibited 72% and 67% by 0.5 mM tolbutamide and 0.1 mM glibenclamide, respectively.

Administration, Oral↗

Stimulation of insulin secretion from isolated rat islets by SaRI 59-801. Relation to cAMP concentration and Ca2+ uptake.

The mechanism of stimulation of insulin release from isolated rat islets by 0.3 mM SaRI 59-801 (DL-alpha-dimethylaminomethyl-2-[ 3-ethyl-5-methyl-4-isoxazoyl]-1H-indole-3-methanol) was investigated, considering cAMP concentration and Ca2+ uptake. Ten millimolar theophylline or 1 mM 1-methyl-3-isobutylxanthine, which inhibit cAMP phosphodiesterase, each greatly increased the stimulation of insulin release by 59-801. Forskolin (0.1 mM), an activator of adenylate cyclase, or 1 mM dibutyryl cAMP also potentiated 59-801, suggesting that 59-801 does not elevate islet cAMP but is potentiated by other compounds that do. Measurement of cAMP in islets by radioimmunoassay confirmed that it was not significantly elevated by 59-801 but was increased sevenfold by forskolin or 1-methyl-3-isobutylxanthine. SaRI 59-801 was not effective in the absence of Ca2+ and presence of 1 mM EGTA. Agents that block entry of Ca2+ into beta-cells, verapamil, nifedipine, or CoCl2, inhibited the release of insulin in response to 59-801. Studies of 45Ca2+ uptake by isolated islets revealed an increased uptake in the presence of 59-801 and blockage of this effect by 50 microM verapamil. Thus, the stimulation of insulin secretion by 59-801 appears to involve a stimulation of Ca2+ uptake rather than an increase of cAMP concentration. The mechanism of stimulation of Ca2+ uptake by 59-801 requires further investigation.

1-Methyl-3-isobutylxanthine↗

Inhibition of gluconeogenesis and glycogenolysis by 2,5-anhydro-D-mannitol.

2,5-Anhydro-D-mannitol (100 to 200 mg/kg) decreased blood glucose by 17 to 58% in fasting mice, rats, streptozotocin-diabetic mice, and genetically diabetic db/db mice. Serum lactate in rats was elevated 56% by 2,5-anhydro-D-mannitol, but this could be prevented by dichloroacetate (200 mg/kg) or thiamin (200 mg/kg). In hepatocytes from fasted rats, 1 mM 2,5-anhydro-D-mannitol inhibited gluconeogenesis from a mixture of alanine, lactate, and pyruvate. It also inhibited glucose production and stimulated lactate formation from glycerol or dihydroxyacetone. Glycogenolysis in hepatocytes from fed rats was markedly inhibited by 1 mM 2,5-anhydro-D-mannitol both in the presence or absence of 1 microM glucagon. 2,5-Anhydro-D-mannitol can be phosphorylated by fructokinase or hexokinase to the 1-phosphate and then by phosphofructokinase to the 1,6-bisphosphate. Rat liver glycogen phosphorylase was inhibited by 2,5-anhydro-D-mannitol 1-phosphate (apparent Ki = 0.66 +/- 0.09 mM) but was little affected by 2,5-anhydro-D-mannitol 1,6-bisphosphate. Rat liver phosphoglucomutase was inhibited by 2,5-anhydro-D-mannitol 1-phosphate (apparent Ki = 2.8 +/- 0.2 mM), whereas 2,5-anhydro-D-mannitol 1,6-bisphosphate served as an alternative activator (apparent K alpha = 7.0 +/- 0.5 microM). Rabbit liver pyruvate kinase was activated by 2,5-anhydro-D-mannitol 1,6-bisphosphate (apparent K alpha = 9.5 +/- 0.9 microM), whereas rabbit liver fructose 1,6-bisphosphatase was inhibited by 2,5-anhydro-D-mannitol 1,6-bisphosphate (apparent Ki = 3.6 +/- 0.3 microM). The phosphate esters of 2,5-anhydro-D-mannitol would, therefore, be expected to inhibit glycogenolysis and gluconeogenesis and stimulate glycolysis in liver.

Animals↗

Toxicological and chemical characterization of the process stream materials and gas combustion products of an experimental low-btu coal gasifier.

The process gas stream of an experimental pressurized McDowell-Wellman stirred-bed low-Btu coal gasifier, and combustion products of the clean gas were characterized as to their mutagenic properties and chemical composition. Samples of aerosol droplets condensed from the gas were obtained at selected positions along the process stream using a condenser train. Mutagenicity was assessed using the Ames Salmonella mammalian microsome mutagenicity assay (TA98, with and without rat liver S9). All materials required metabolic activation to be mutagenic. Droplets condensed from gas had a specific mutagenicity of 6.7 revertants/microgram (50,000 revertants/liter of raw gas). Methylnaphthalene, phenanthrene, chrysene, and nitrogen-containing compounds were positively identified in a highly mutagenic fraction of raw gas condensate. While gas cleanup by the humidifier-tar trap system and Venturi scrubber led to only a small reduction in specific mutagenicity of the cooled process stream material (4.1 revertants/microgram), a significant overall reduction in mutagenicity was achieved (to 2200 revertants/liter) due to a substantial reduction in the concentration of material in the gas. By the end of gas cleanup, gas condensates had no detectable mutagenic activity. Condensates of combustion product gas, which contained several polycyclic aromatic compounds, had a specific mutagenicity of 1.1 revertants/microgram (4.0 revertants/liter). Results indicate that the process stream material is potentially toxic and that care should be taken to limit exposure of workers to the condensed tars during gasifier maintenance and repair and to the aerosolized tars emitted in fugitive emissions. Health risks to the general population resulting from exposure to gas combustion products are expected to be minimal.

Air Pollutants↗

Comparative mutagenicity of a coal combustion fly ash extract in Salmonella typhimurium and Chinese hamster ovary cells.

The dichloromethane extract of a coal combustion fly ash sample obtained from an experimental fluidized bed coal combustor was tested for mutagenicity in Salmonella typhimurium and cultured Chinese hamster ovary (CHO) cells. The extract was directly mutagenic in S typhimurium strain TA98 and the nitroreductase deficient strains TA98NR and TA98/1,8DNP6. The mutagenicity observed in TA98NR and TA98/1,8DNP6 was lower than that in TA98. Addition of exogenous Aroclor 1254-induced rat liver supernatant (liver S9) decreased the bacterial mutagenicity of the extract. A different mutagenic response was observed in CHO cells. In the absence of liver S9, although the extract was cytotoxic to CHO cells, no significant mutagenicity was observed. Addition of exogenous liver S9 decreased the cytotoxicity and increased the mutagenicity at both Na+-K+-ATPase and hypoxanthine-guanine phosphoribosyl transferase (HGPRT) gene loci in CHO cells. Using gas chromatography/mass spectrometry (GC/MS) and tandem quadruple mass spectrometry, a number of polynuclear aromatic hydrocarbons (PAHs) and nitrated PAHs (nitro-PAHs) were tentatively identified and quantitated. A possible explanation of the difference in bacterial and mammalian mutagenicity of the extract is that the bacterial mutagenicity was induced by the nitro-PAHs that are potent bacterial mutagens and mammalian mutagenicity was induced by both PAHs and nitro-PAHs that are promutagens.

Animals↗

Fractionation, chemical analysis, and mutagenicity testing of low-Btu coal gasifier tar.

A tar from a low-Btu coal gasifier was subjected to parallel fractionation, chemical analysis, and bacterial mutagenicity (Salmonella) assay. Like other coal-derived tars, it was a complex mixture containing some high-molecular-weight material and several classes of organic compounds as major constituents. The results of bacterial mutagenicity testing of fractions and subfractions of the tar suggest that neutral nitrogen-containing compounds, phenols, organic bases, polycyclic aromatic hydrocarbons, and some uncharacterized high-molecular-weight materials are mutagenic to Salmonella and therefore are potentially mutagenic in higher systems.

Chemical Phenomena↗

A simple dynamic flow-through exposure system for assessment of biological activity of complex organic mixtures to mammalian cells in vitro.

A system for in vitro exposure of lung epithelial cells and Chinese hamster ovary cells maintained at an air-medium interface to volatile organic compounds has been developed. The system has been used for exposure of cells to phenol (vapor pressure at 40 degrees C = 1.6 mm Hg) and to a complex mixture of organic compounds (vapor pressure range at 32 degrees C = 0.17 to 269 mm Hg). A linear relationship was found between vapor generator air flow rate (0.25 to 1.0 L/min at 39 degrees C) and exposure chamber phenol concentration. The relationship between generator air flow rate (0.5 to 1.0 L/min at 39 degrees C) and concentration of the complex mixture in the exposure chamber was also linear. Gas chromatographic analyses of chamber exhaust indicated that a majority of the compounds present in the crude mixture had been volatilized and made available to the cells in the chamber. This exposure system appears suitable for screening of complex mixtures of volatile organic pollutants for biological activity in mammalian cells in culture.

Air Movements↗

Applying management information systems to staffing.

A management information system (MIS) is a tool for managing resources effectively. After reviewing some concepts and principles for effective data management, Hanson clearly applies the concepts to nurse staffing systems, which manage human resources. He defines a seven-step process for establishing an MIS, from defining the management objective to implementing the system. Pointing out that an MIS need not be computerized to be effective, Hanson presents a positive perspective and clarifies some often-misconceived notions about management information systems and the paper printouts they generate. In the next issue of JONA, a second article by Hanson will take a more detailed look at the variety, use, and usefulness of staffing statistics available from an MIS for staffing. These articles are based on material in a forthcoming book, Management Systems for Nursing Service Staffing, to be published by Aspen Systems Corporation, Rockville, Maryland.

Information Systems↗

Effects of an insertion mutation in a locus affecting pyridine nucleotide transhydrogenase (pnt::Tn5) on the growth of Escherichia coli.

The effects of a pnt::Tn5 insertion mutation on the growth of strains lacking phosphoglucoisomerase or glucose 6-phosphate dehydrogenase were examined. The results support the idea that the energy-linked transhydrogenase is an important source of reduced nicotinamide adenine dinucleotide phosphate for Escherichia coli under some conditions.

DNA Transposable Elements↗