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Biomedical subjects

D R Clark

Publications and source records attributed to D R Clark.

At least 55 records · Page 3Linked to original sources

Limits of detection and quantification, as applied to an assay for digoxin.

The low-range sensitivity of a drug assay in routine use is an important aspect of that assay's clinical usefulness. We define three concepts for determining low range sensitivity: LC, the detection threshold; LD, the lower limit of "virtually ensured" detection; and LQ, the limit of quantitative determination. To illustrate these concepts, we apply them to a radioimmunoassay for digoxin, and show that for standards ranging from 0.3 to 5.0 micrograms/L, the LQ is 0.35 micrograms/L (+/- 10%).

Digoxin↗

Effects of DDE and PCB (Aroclor 1260) on experimentally poisoned female little brown bats (Myotis lucifugus): lethal brain concentrations.

Adult female little brown bats (Myotis lucifugus) were collected in a church attic in North East, Cecil County, Md. Mealworms (Tenebrio molitor) containing organochlorine pollutants were fed to the bats as follows: 5 bats were dosed at 480 ppm DDE, 12 at 150 ppm DDE, 5 at 1000 ppm polychlorinated biphenyl (PCB; Aroclor 1260), and 12 at 15 ppm PCB. Seven other bats were fed untreated mealworms. The objective was to elevate brain levels of DDE and PCB to lethality and measure these concentrations. During 40 d of dosage, one DDE-dosed bat and two PCB-dosed bats died after exhibiting the prolonged tremor that characterizes organochlorine poisoning. After dosage, surviving bats were starved to elevate brain levels of toxicants, and three additional DDE-dosed bats had tremors before dying. The mean brain concentration of DDE diagnostic of death was estimated as 603 ppm, range 540-670 ppm. This mean is 16-18% higher than means for Mexican free-tailed bats (Tadarida brasiliensis) and common grackles (Quiscalus quiscula), and may indicate less sensitivity. Lethal brain concentrations of Aroclor 1260 were 1300 and 1500 ppm. Such values appear to be higher than values (Aroclor 1254) for brown-headed cowbirds (Molothrus ater). During starvation, DDE-dosed bats lost weight about 24% faster than controls. If smaller amounts of stored DDE cause increases in metabolic rates of nonfeeding bats, as during hibernation or migration, the result could be premature energy depletion and increased mortality.

Animals↗

Orthotics for the mentally retarded.

Although only a portion of mentally retarded persons need orthotic management, these services can help achieve increased function and independence or make custodial care easier for the health care team or family.

Humans↗

Abelson murine leukemia virus mutants deficient in kinase activity and lymphoid cell transformation.

Abelson murine leukemia virus transforms both lymphoid cells and fibroblasts in vitro and induces a unique type of thymus-dependent lymphoma in vivo. Four fibroblast-transforming strains of Abelson murine leukemia virus were identified, based on the sizes of the Abelson murine leukemia virus-specific phosphoproteins produced by these isolates. Two of these strains, the standard P120- and the P160-producing viruses, transformed lymphoid cells efficiently in vitro and induced Abelson disease in vivo. Two other strains, which synthesized small Abelson murine leukemia virus-specific proteins with molecular weights of 90,000 (P90) and 100,000 (P100), transformed lymphoid cells very poorly both in vitro and in vivo. The reduced oncogenic potentials of these isolates were correlated with a high level of synthesis of fairly unstable P90 and P100. In addition, neither P90 nor P100 functional efficiently in protein kinase assays. The correlation of abnormal metabolism and deficient protein kinase activity with the reduced oncogenic potentials of these virus strains supported a direct role for these proteins and the kinase activity in transformation. Furthermore, these results suggested that the requirements for lymphoid cell transformation and fibroblast transformation are different.

Abelson murine leukemia virus↗

Organochlorine residues in eggs of loggerhead and green sea turtles nesting at Merritt Island, Florida--July and August 1976.

Eggs from nine clutches of loggerhead turtles (Caretta caretta) and two clutches of green turtles (Chelonia mydas) were collected as they were laid on Merritt Island, Florida. Eggs were incubated, frozen, and analyzed for organochlorines. Levels of DDE and PCB, the major contaminants, averaged less than 0.08 ppm in loggerhead eggs and were even lower in green turtle eggs. These concentrations are far below levels thought to be potentially harmful. Loggerhead eggs were frozen after 43-52 days incubation; both DDE and PCB declined significantly during this interval. Authors estimate that DDE averaged about 0.2 ppm in loggerhead eggs when they were laid. DDE levels in eggs of both turtle species were less than levels in eggs of crocodiles (Crocodylus acutus) from Everglades National Park and in eggs of 13 species of aquatic birds nesting on Merritt Island. The remarkably low residues in the turtle eggs probably indicate that, when not nesting, the turtles live and feed in areas remote from Florida.

Animals↗

Organochlorine pollutants in small cetaceans from the Pacific and south Atlantic Oceans, November 1968-June 1976.

Organochlorine residues were analyzed in blubber, brain, or muscle tissues of 69 individuals representing 10 species of small cetaceans. Collections were made from November 1968 through June 1976 at localities in the Eastern Tropical Pacific and along the coasts of California, Hawaii, Japan, and Uruguay, Relations of residue concentrations between tissues are described for DDE and PCBs in two dolphin species. sigma DDT and PCB residues in blubber of most of the 19 individuals of the five southern California species sampled exceed concentrations that are associated with reproductive impairment in pinnipeds, although the nature of such associations is not well defined. The sigma DDT residue of 2,695 ppm in blubber of one California coastal Tursiops truncatus is one of the highest concentrations reported in tissues of members of any population of wild mammals. Except for one rough-toothed dolphin (Steno bredanensis) from Maui, Hawaii, all individuals from all localities surveyed were contaminated with organochlorine compounds. Seventeen different organochlorines were detected; greatest diversity occurred near Japan and California. This is the first report of several of these compounds in tissues of any species of marine mammals. The o,p'-isomers and metabolites of DDT were detected unusually frequently. Ratios of p,p'-DDT to p,p'-DDE in blubber of cetaceans from waters off countries where use of this pesticide has been relatively recent and ongoing were at least an order of magnitude higher than in cetaceans from United States waters.

Analysis of Variance↗

Dieldrin and heptachlor residues in dead gray bats, Franklin County, Missouri--1976 versus 1977.

Lethal dieldrin concentrations were found in the brains of dead gray bats (Myotis grisescens) collected during 1976 and 1977 beneath a maternity roost in a Missouri cave. In addition, residues of heptachlor epoxide, oxychlordane, cis-chlordane, and trans-nonachlor increased significantly in both brains and carcasses of bats collected during 1977. These increases appear to reflect a switch by local farmers from aldrin, dieldrin's parent compound, to heptachlor for the control of cutworms. They also constitute an additional threat to this colony of this endangered bat species.

Animals↗

Myocardial capillary density and muscle fibre size in rats born and raised at simulated high altitude.

Rats were born in a hypobaric chamber at a pressure of 500 mmHg and kept there at 460 mmHg for 5, 9 or 13 weeks. The myocardial capillary bed was labelled by perfusion with India ink. The density of myocardial capillaries and the area of cross-section of myofibres was estimated from histological sections. In the left ventricle there was a steady reduction in capillary density with increasing age which was similar in test and control rats. There was also an increase in myofibre size which was similar in test and controls. Hypoxia therefore failed to induce capillary proliferation or a reduction in myofibre diameter in the left ventricle and this is reflected in a constant capillary:fibre ratio. In the right ventricle, ventricular hypertrophy in the hypoxic rats induced a striking reduction in capillary density due to a two-fold increase in myofibre size. There was nevertheless some degree of capillary proliferation, probably a consequence of hypertrophy rather than the direct influence of hypoxia.

Aging↗

Dieldrin-induced mortality in an endangered species, the gray bat (Myotis grisescens).

Brains of juvenile gray bats, Myotis grisescens, found dead beneath maternity roosts in two Missouri caves contained lethal concentrations of dieldrin. One colony appeared to be abnormally small, and more dead bats were found a year after the juvenile bats had been collected. This is the first report to link the field mortality of bats directly to insecticide residues acquired through the food chain.

Aldrin↗

Purification, characterization, and action-pattern studies on the endo-(1 linked to 3)-beta-D-glucanase from Rhizopus arrhizus QM 1032.

The extracellular (1 linked to 3)-beta-D-glucanase [(1 linked to 3)-beta-D-glucan glucanohydrolase, EC 3.2.1.6] produced by Rhizopus arrhizus QU 1032 was purified 305-fold in 70% overall yield. This preparation was found to be homogeneous by ultracentrifugation (sedimentation velocity and equilibrium studies), electrophoresis on acrylamide gel with normal, sodium dodecyl sulfate, and urea-acetic acid gels, and upon isoelectric focusing. The amino acid composition of the enzyme has been determined and it possesses a carbohydrate moiety compose of mannose and galactose (in the ratio approximately 5:1) that is linked to the protein through a 2-acetamido-2-deoxyglucose residue. The molecular weight, as determined by equilibrium sedimentation, is 28,800 and this number was confirmed by electrophoresis on gels of sodium dodecyl sulfate. The enzyme does not possess subunit structure. It hydrolyzes its substrates with retention of configuration and possesses transglycosylating ability. The rates of hydrolysis of a wide variety of substrates were determined, and its action pattern on a series of oligosaccharides containing mixed (1 linked to 3)-, (1 linked to 4)-, and (1 linked to 6)-beta-D-glucopyranosyl residues was investigated. The enzyme favors stretches of beta-D-(1 linked to 3) linkages, but it can hydrolyze beta-D-(1 linked to 4) linkages that are flanked on the non-reducing side with stretches of beta-D-(1 linked to 3) links. The enzyme will not act on (1 linked to 6)-beta-D-glucosyl linkages located in stretches of beta-D-(1 linked to 3) and will not act on (1 linked to 3) beta-D-glycosidic linkages involving sugars other than D-glucose.

Glucan Endo-1,3-beta-D-Glucosidase↗