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D L Hardy

Publications and source records attributed to D L Hardy.

6 recordsLinked to original sources
PubMed1992

The rapid response of isolated mitochondrial particles to 0.1 nM-tri-iodothyronine correlates with the ADP-ribosylation of a single inner-membrane protein.

Under defined conditions liver mitochondria from hypothyroid rats show an apparent lowering of the ADP/O ratio, which can be corrected by addition in vitro of 0.1 nM-tri-iodothyronine (T3). Nicotinamide prevents this restoration by hormone, lowers the ADP/O ratio of euthyroid-rat mitochondria to hypothyroid-rat values and induces T3-sensitivity in euthyroid-rat mitoplasts indistinguishable from that found with hypothyroid-rat preparations. Incorporation into the trichloroacetic-acid insoluble fraction of mitoplasts and hypothyroid-rat mitochondria of radiolabel from [adenine-14C]-NAD+ was stimulated by T3: this stimulation was abolished by nicotinamide. The findings strongly suggest that this incorporation occurs external to the matrix. Confirming the work of others, PAGE of radiolabelled mitoplasts shows alkali-labile modification of a major species of approx. 30 kDa: both nicotinamide and T3 abolish this modification. By contrast, T3 promotes incorporation of label into a single major 11 kDa species: this incorporated label is somewhat acid-labile, and the incorporation is abolished by nicotinamide. Comparative electrophoresis of purified sub-mitoplast fractions show that the 11 kDa species is in the inner membrane and absent from the matrix. The findings are consistent with a receptor-mediated ADP-ribosylation mechanism for the rapid action of T3 on mitochondria.

Adenosine Diphosphate↗
PubMed1991

The characterization of a new enzyme from rat liver mitochondria, oligophosphoglyceroyl-ATP 3'-phosphodiesterase.

By using an assay based on the precipitation of intact 14C-labelled substrate, an activity has been located in the mitochondrial fraction of rat liver which selectively hydrolyses the 3' ester link in the fairly recently discovered oligomeric tetraphosphate derivative of ATP and glyceric acid for which the structure 3-phospho[glyceroyl-gamma-triphospho-5'-adenosine-3'-3-phospho]n-glyceroyl- gamma-triphospho-5'-adenosine has been proposed [Hutchinson, Morris & Mowbray (1986) Biochem. J. 234, 623-627]. This enzyme activity (Mr 85,000) has been purified approx. 30-fold from washed mitochondria by (NH4)2SO4 precipitation and f.p.l.c. The apparent Km for substrate (adenosine equivalents) is around 35 microM. The recovery of total activity is about 20%, and this, allied to the relatively low Vmax. found in contrast with the rapid turnover of oligomer seen in post-ischaemic tissues, suggests that some activating factors have been lost in purification. Percoll-gradient studies confirm that the activity is mitochondrial and not lysosomal or endoplasmic-reticular. The activity is latent in intact mitochondria; it is not, however, associated with intact inner-membrane vesicles but released during their preparation, implying an intermembrane-space location. The product of the enzyme is proposed to be the monomeric unit 3-phosphoglyceroyl-gamma-triphospho-5'-adenosine, from which digestion with snake-venom phosphodiesterase releases ADP.

Animals↗
PubMed1986

Fatal rattlesnake envenomation in Arizona: 1969-1984.

Case histories of the last nine fatalities (1969-1984), in which the cause of death on the State of Arizona Certificate of Death was snakebite, were reviewed. Six males and three females ranged in age from 2 to 77 years, and were bitten between 0800-2100 hours from April to September. Bites in three adult males were "illegitimate" and of these, two were by captive Mojave rattlesnakes, Crotalus s. scutulatus. The latter two victims had been bitten previously and remained at home, refusing treatment. In the other seven victims, the snakes involved were not identified. However, all localities where bites occurred were within the geographical and altitudinal range for Crotalus atrox and C. s. scutulatus. The apparent cause of death was prolonged hypotension with major organ system failure in five, intestinal hemorrhage in one, and was unknown in three. Major organs were involved as follows: cardiac failure (two); noncardiac pulmonary edema (two); renal failure (two); unconsciousness with airway obstruction and brain damage (two); and coagulopathy with multiple hemorrhage sites (one). Seven of the nine deaths appeared to be preventable. Four delayed going to a medical facility and six did not have hypotension corrected. Antivenin was not administered early (first four hours) or in adequate amounts (10 vials or more) because of delayed arrival in five or physician's decision in four. Pre-existing cardiac disease contributed to death of two victims. Rattlesnake bite victims should not delay travel to a medical facility and hypotension must be treated aggressively and appropriately.

Adult↗