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Biomedical subjects

M A Dunn

Publications and source records attributed to M A Dunn.

At least 37 records · Page 2Linked to original sources
PubMed1993

A low-temperature-responsive translation elongation factor 1 alpha from barley (Hordeum vulgare L.).

A cDNA clone (pBLT63) encoding a protein synthesis elongation factor 1 alpha (EF-1 alpha) was isolated from a low-temperature winter barley shoot meristem library by differential screening. The nucleotide sequence of the coding region of the low-temperature-induced barley gene shows very high homology with two EF-1 alpha plant genes from tomato and Arabidopsis. The barley genome contains an EF-1 alpha gene family situated on the short arm of chromosome 2 and the long arm of chromosome 5.

Amino Acid Sequence↗
PubMed1993

Molecular analysis and spatial expression pattern of a low-temperature-specific barley gene, blt101.

A cDNA clone of the previously unreported low-temperature-induced gene blt101 was isolated after a differential screen of a cDNA library prepared from low-temperature (6 degrees C day/2 degrees C night) grown barley shoot meristems. Southern blot analysis of barley ditelosomic addition lines was used to assign this single-copy gene to the long arm of chromosome 4. Analysis of steady-state levels of blt101 mRNA showed the induction of this transcript in shoot meristems upon transfer of barley (cv. Igri) plants from control (20 degrees C/15 degrees C) to low (6 degrees C/2 degrees C) temperature treatment. Further, the high level of this transcript is maintained at low temperatures but is reduced on transfer from low to control temperatures. The gene is not induced by drought or by foliar application of ABA. Analysis of segregating doubled haploid lines shows that there is no specific association of this gene with either spring/winter growth habit or frost hardiness. Examination of the spatial expression pattern revealed ubiquitous expression of blt101 in low-temperature (6 degrees C/2 degrees C) grown barley shoot meristems, mature leaves and roots.

Abscisic Acid↗
PubMed1993

Dietary aluminum chloride reduces the amount of intestinal calbindin D-28K in chicks fed low calcium or low phosphorus diets.

The mechanism of aluminum (Al) toxicity may involve disturbances in calcium (Ca) metabolism. Aluminum compounds have been reported to reduce vitamin D-dependent Ca absorption in chicks, rats and humans. To investigate the mechanism by which Al reduces Ca absorption, we studied the effect of dietary aluminum chloride (AlCl3) on the relative amounts of intestinal calbindin D-28K in chicks fed diets varying in Ca and phosphorus concentration. AlCl3 was added so that Al constituted 0, 0.15 or 0.3 g/100 g of diets that were either adequate, low in Ca, low in P, or contained supplemental P. Diets were fed for 2 wk. Intestinal calbindin D-28K levels were assayed using SDS-PAGE and 45Ca binding to Western blots. Added dietary Al greatly reduced the amount of intestinal calbindin in chicks fed adequate diets, low Ca diets, or low P diets. When diets with supplemental P were fed, little calbindin was evident with or without added Al. Tibia ash, body weight and food intake were also reduced (P < 0.05) by added Al. These results indicate that dietary AlCl3 inhibits vitamin D-dependent Ca absorption by reducing the amount of intestinal calbindin D-28K. Aluminum, therefore, may interfere with the body's ability to regulate intestinal calbindin D-28K levels. This could have implications for other tissues that contain substantial levels of calbindin D-28K.

Aluminum Chloride↗
PubMed1993

Diazepam as a treatment for nerve agent poisoning in primates.

Diazepam is known to decrease organophosphate nerve agent-induced convulsions, neuropathology, and lethality in rhesus monkeys. We report that, when added to the previously fielded treatment regimen (pyridostigmine, atropine, and pralidoxime chloride), diazepam significantly protects the performance of rhesus monkeys trained in an equilibrium task, the Primate Equilibrium Platform (PEP), against deficits induced by the nerve-agent soman. If administered soon enough to minimize the occurrence of convulsions, diazepam should increase the probability of mission accomplishment and eventual complete recovery from nerve agent poisoning. Diazepam was fielded by the United States military services during Operations Desert Shield and Storm for the treatment of possible organophosphate toxicity.

Animals↗
PubMed1992

Effects of dietary aluminum and niacin on chick tibiae.

Effects of dietary aluminum chloride and niacin on bone mineral content and bone structural measurements were studied using young male Leghorn chicks. Standard chick rations containing .8% Ca and .4 or .5% available P were fed as control diets in three experiments. Experimental diets contained .05, .1, or .3% Al, or 1.0 or 1.5% niacin, or both and were fed for 2 wk. Tibia weights were decreased by 1.5% niacin, .3% Al, and by .1% Al plus 1.5% niacin (P less than .05). Breaking strength of tibiae was decreased (P less than .05) by 1.5% niacin, .1% Al, and .1% Al plus 1.5% niacin. Ultimate stress, which is force per unit area, was decreased by .3% Al and .05% Al plus 1.5% niacin (P less than .05). Niacin had no significant effect on bone mineral content. In Experiment 3, .3% Al decreased P, Ca, Mg, and Zn content of the tibiae (P less than .05). These findings indicate that feeding high levels of supplemental niacin results in decreased bone strength in chicks with no change in mineral content of the tibiae. Aluminum fed at levels of .3% of the diet causes a decrease in bone strength with concomitant changes in bone mineral content.

Aluminum↗
PubMed1991

Pyridostigmine used as a nerve agent pretreatment under wartime conditions.

OBJECTIVE: To determine the adverse effects of pretreatment with pyridostigmine bromide for nerve agent exposure during wartime. DESIGN: A retrospective study. SETTING: Southwest Asia. PARTICIPANTS: Personnel who provided medical support to the XVIII Airborne Corps. These medical officers supplied information pertaining to symptoms and disposition of 41,650 soldiers who received pyridostigmine at the onset of hostilities of Operation Desert Storm. INTERVENTION: Pyridostigmine bromide, 30 mg orally, was self-administered every 8 hours while under the threat of nerve agent attack (for 1 to 7 days). MAIN OUTCOME MEASURE: Physiologic changes attributable to pyridostigmine that resulted in need for medical attention, discontinuation of the drug, hospitalization, and/or evacuation from Southwest Asia. RESULTS: About half of the population noted physiologic changes that were not incapacitating, such as increased flatus, abdominal cramps, soft stools, and urinary urgency. Approximately 1% of the soldiers believed they had effects that warranted medical attention, but fewer than 0.1% had effects sufficient to discontinue the drug. Nonincapacitating symptoms often occurred; however, military mission performance was not impaired. CONCLUSION: While under the threat of nerve agent attack, pyridostigmine can be administered to virtually all soldiers.

Chemical Warfare Agents↗
PubMed1991

Nucleotide and derived amino acid sequence of the cyanogenic beta-glucosidase (linamarase) from white clover (Trifolium repens L.).

The nucleotide sequence and derived amino acid sequence of two different beta-glucosidase cDNA clones were determined. One clone (TRE104) was identified as the cyanogenic beta-glucosidase by homology with the N-terminal and internal peptide amino acid sequence of the purified enzyme. The biological function of the other beta-glycosidase (TRE361) is not known. Co-segregation of genomic restriction fragments uniquely identified by each cDNA clone shows that these two genes are linked in the white clover genome. Both TRE104 and TRE361 fragments co-segregate with cyanogenic beta-glucosidase activity. Extensive homology was found between the white clover beta-glucosidase sequences and a group of prokaryote and mammalian beta-glycosidases. This group of sequences has no homology with a separate set of beta-glucosidase genes isolated from fungi and the thermophilic bacterium Clostridium thermocellum.

Amino Acid Sequence↗
PubMed1991

Nucleotide sequence and molecular analysis of the low temperature induced cereal gene, BLT4.

The nucleotide sequence and derived amino acid sequence of a cDNA clone (BLT4) for a low temperature induced barley gene were determined. This gene, together with a small family of related genes, was shown to reside on chromosome 3. The BLT4 clone has homology with genes in wheat and oats. Its expression was studied in oats and in barley doubled haploid lines segregating for spring/winter habit and for frost hardiness. These analyses show that elevated steady state levels of BLT4 mRNA are produced in shoot meristematic tissue after 3 days low positive temperature treatment. The low temperature response was found in all barley doubled haploid lines and was therefore not associated specifically with either the spring/winter habit or frost hardiness. Elevated levels of BLT4 mRNA were also seen in drought-stressed barley and it is likely that this is a gene encoding a low molecular weight protein that is responsive to dehydrative stresses, such as cold and drought.

Amino Acid Sequence↗
PubMed1991

Kinetics of copper metabolism in rats: a compartmental model.

Model-based compartmental analysis was used to describe data on the whole body kinetics of copper metabolism in rats. Data were collected on recovery of radio-copper in plasma, liver, skin, skeletal muscle, bile, and feces for 3 days after the injection of 10 micrograms iv of copper labeled with 64Cu. Data on copper masses and on 64Cu kinetics were analyzed by the stimulation, analysis, and modeling computer programs. Observed data were fit to a 16-component "working hypothesis" model; fractional transfer coefficients were estimated, and steady-state compartment masses and copper transfer rates were calculated. The model postulates a rapid turnover of plasma nonceruloplasmin (NCp) copper (8.5 h-1), which exchanged a large amount of copper with extrahepatic tissues (16 micrograms/h) as well as liver (13 micrograms/h). In comparison, ceruloplasmin (Cp) transferred relatively little copper to tissues (less than 1 microgram/h). NCp copper is postulated to be the precursor for biliary copper. Regarding the intracellular metabolism of copper in hepatic and extrahepatic tissues, the data were compatible with a faster turning-over compartment that exchanged copper with NCp and a slower turning-over compartment with input from Cp. In the liver, the slower turning-over compartment was the copper present in peak II (mol mass 30,000-40,000 Da); this received much of its input from the faster turning-over compartment (peak III), which was hypothesized to represent, in large part, copper in metallothionein.

Animals↗
PubMed1991

Medical defense against blistering chemical warfare agents.

First used in World War I, chemical blistering agents present a serious medical threat that has stimulated renewed interest in the light of extensive use in recent conflicts. Current medical management cannot yet prevent or minimize injury from the principal agent of concern--sulfur mustard. Research directed at this goal depends on defining effective intervention in the metabolic alterations induced by exposure to sulfur mustard.

Arsenic Poisoning↗
PubMed1990

Restriction fragment length polymorphism segregation analysis of the Li locus in Trifolium repens L.

The Li locus in white clover controls the presence of cyanogenic beta-glucosidase (linamarase) activity in leaf tissue, such that plants homozygous for the 'null' allele (li) have no linamarase activity in this tissue. The isolation of a cDNA clone from linamarase mRNA is described. The cDNA clone is used to further characterise alleles of the Li locus. Northern blot analysis shows that plants homozygous for the 'null' allele (li li) produce very reduced levels of mRNA which hybridises to the cDNA. Heterozygous plants (Li li), which have intermediate levels of enzyme activity, produce intermediate levels of mRNA. Southern blot analysis of Hind III digested genomic DNA shows that the white clover genome contains three genes with homology to the linamarase cDNA and that at least two of these genes segregate independently. Analysis of the cosegregation of linamarase activity and the presence of genomic restriction fragments identifies the genomic sequence specifying linamarase structure and indicates either a structural or cis acting control function of the Li locus.

Alleles↗
PubMed1989

Progress in medical defense against nerve agents.

For nearly 50 years, nerve agents have constituted a serious threat that has stimulated extensive efforts to develop effective medical countermeasures. Recent progress in producing pharmacologic defenses suggests that humans can be largely protected from the lethal and prolonged incapacitating effects of these compounds on a chemical battlefield. Current research on new approaches to binding and inactivating nerve agents may further decrease their potential as a threat against protected persons.

Animals↗
PubMed1989

Kinetics of zinc metabolism in the rat: effect of dibutyryl cAMP.

N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (Bt2cAMP) administration to rats is shown to reduce serum zinc levels and increase liver zinc and metallothionein significantly. Such redistribution is similar to that seen in the acute phase response to stress. To determine the sites of regulation of zinc metabolism involved in zinc redistribution, we compared the kinetics of intravenously administered 65Zn between control and Bt2cAMP-treated rats. 65Zn disappeared more rapidly from the plasma of Bt2cAMP rats, whereas 65Zn content of liver and liver metallothionein was increased. 65Zn in spleen and bone marrow also increased. No change was seen in muscle or kidney, and 65Zn content decreased in skin, bone, small intestine, and feces. These kinetic data were integrated into two compartmental models describing zinc metabolism in control and Bt2cAMP-treated states. Models were constructed using the SAAM and CONSAM modeling programs. Comparison of models suggest several sites of regulation due to Bt2cAMP. Zinc uptake into liver metallothionein from both plasma and other zinc pools within the liver was increased, whereas the release of metallothionein-bound zinc to plasma decreased. These changes increased liver zinc at the expense of plasma zinc, tissue zinc (principally skin, bone, and small intestine), and fecal zinc excretion. Bone marrow, spleen, and muscle were protected against zinc loss due primarily to decreased rates of tissue zinc loss. It was also postulated that Bt2cAMP increased the transfer of liver zinc to secreted alpha 2-macroglobulin. These results demonstrate that Bt2cAMP-induced zinc redistribution is tissue specific and related in part to metallothionein synthesis.

Animals↗
PubMed1989

T lymphocyte subset modulation of hepatic fibroblast function in murine schistosomiasis.

We have previously shown that co-culture of T cell enriched spleen lymphocytes can reduce collagen synthesis and stimulate proliferative activity by liver fibroblasts from S. mansoni infected mice. The present study examines which subset of T cells is responsible for this modulation. Co-culture of fibroblasts with the total T cell population lead to significant stimulation in fibroblast proliferative activity and a significant decrease in the incorporation of 14C-proline into collagenase-sensitive protein. There was virtually no effect on total incorporation of 14C-proline in non-collagen proteins. An additional significant increase in fibroblast proliferative activity and another significant decrease in collagen synthesis accompanied by a 2-fold increase in non-collagen protein production was noted when fibroblasts were co-cultured with Lyt-1+ cells. Co-culture of fibroblasts with Lyt-2+ cells did not differ significantly from co-culture with total T cells. Mitomycin treatment of the lymphocytes blunted their specific effects, suggesting that proliferation of T cells is required for maximal exertion of their regulatory activity. These results suggest that the T cells which mediate these effects belong to the Lyt-1+ helper class and are distinct from the Lyt-2+ suppressor cells.

Animals↗
PubMed1988

Effect of colchicine on collagen synthesis by liver fibroblasts in murine schistosomiasis.

Colchicine, an antimicrotubular agent, was shown to block the transcellular movement of certain structural macromolecules such as collagen. In the present study, the effect of colchicine on collagen synthesis and secretion by monolayer cultures of fibroblasts from livers of mice infected with Schistosoma mansoni was investigated. The effect of colchicine on proliferation of these fibroblasts was studied as well. Collagen and non-collagen protein synthesis was measured by incubating cultures with [14C]proline and measuring the incorporation of radioactivity into these protein fractions in both culture media and cell layers. Proliferation was measured by [3H]thymidine uptake. The isolated fibroblasts actively formed collagen and secreted most of it into the culture medium; 10-20% of the collagenase-sensitive radioactive protein remained in the cell layer. The addition of colchicine to culture medium led to selective inhibition of collagen formation with negligible effects on non-collagen protein synthesis. Fibroblast proliferation was also reduced by colchicine treatment. Both inhibition of collagen synthesis and inhibition of fibroblast proliferation were dose-dependent. Comparison of medium and cell layer collagen radioactivity confirmed inhibition of synthesis rather than only inhibition of secretion. These data suggest that colchicine has a specific effect on synthesis of collagen and proliferative activity by fibroblasts from S. mansoni-infected liver and may, therefore, be useful in modulating schistosomal hepatic fibrosis.

Animals↗