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D Shannon

Publications and source records attributed to D Shannon.

At least 19 recordsLinked to original sources
PubMed1999

Quantitation and origin of the mitochondrial membrane potential in human cells lacking mitochondrial DNA.

Mammalian mitochondrial DNA (mtDNA) encodes 13 polypeptide components of oxidative phosphorylation complexes. Consequently, cells that lack mtDNA (termed rho degrees cells) cannot maintain a membrane potential by proton pumping. However, most mitochondrial proteins are encoded by nuclear DNA and are still imported into mitochondria in rho degrees cells by a mechanism that requires a membrane potential. This membrane potential is thought to arise from the electrogenic exchange of ATP4- for ADP3- by the adenine nucleotide carrier. An intramitochondrial ATPase, probably an incomplete FoF1-ATP synthase lacking the two subunits encoded by mtDNA, is also essential to ensure sufficient charge flux to maintain the potential. However, there are considerable uncertainties about the magnitude of this membrane potential, the nature of the intramitochondrial ATPase and the ATP flux required to maintain the potential. Here we have investigated these factors in intact and digitonin-permeabilized mammalian rho degrees cells. The adenine nucleotide carrier and ATP were essential, but not sufficient to generate a membrane potential in rho degrees cells and an incomplete FoF1-ATP synthase was also required. The maximum value of this potential was approximately 110 mV in permeabilized cells and approximately 67 mV in intact cells. The membrane potential was eliminated by inhibitors of the adenine nucleotide carrier and by azide, an inhibitor of the incomplete FoF1-ATP synthase, but not by oligomycin. This potential is sufficient to import nuclear-encoded proteins but approximately 65 mV lower than that in 143B cells containing fully functional mitochondria. Subfractionation of rho degrees mitochondria showed that the azide-sensitive ATPase activity was membrane associated. Further analysis by blue native polyacrylamide gel electrophoresis (BN/PAGE) followed by activity staining or immunoblotting, showed that this ATPase activity was an incomplete FoF1-ATPase loosely associated with the membrane. Maintenance of this membrane potential consumed about 13% of the ATP produced by glycolysis. This work has clarified the role of the adenine nucleotide carrier and an incomplete FoF1-ATP synthase in maintaining the mitochondrial membrane potential in rho degrees cells.

Adenosine Triphosphatases↗
PubMed1998

In vitro metabolism of 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naphthyridin-5(7H)- one, a topical antipsoriatic agent. Use of precision-cut rat, dog, monkey and human liver slices, and chemical synthesis of metabolites.

The metabolism of SCH 40120, which is the clinically effective antipsoriatic drug 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzol[b][1,8]naphthyrid in-5(7H)-one, was determined in vitro. Rat, dog, cynomolgus monkey, and human liver slices hydroxylated the aliphatic, cyclohexenyl ring of the drug and conjugated the resulting carbinol. The identified metabolites comprised the corresponding 6-, 7-, and 9-carbinols, the glucuronide of the 6-carbinol, and the 6-ketone derived from the parent drug. Although the three carbinols appeared in the liver isolates of all species studied, the relative amounts of these metabolites varied across species. With a high, non-physiological ratio of substrate to liver, the 6-carbinol and its glucuronide were the major metabolites in human and monkey, whereas the 6-ketone was a minor metabolite in dog. Containing a stereogenic axis and center, the 6-carbinol existed as diastereomeric atropisomers. Its structure was established by 13C and 1H NMR spectroscopy, mass spectrometry, and comparison to an authentic sample.

Animals↗
PubMed1998

Culture and early infancy among central African foragers and farmers.

Everyday infant experiences among the Aka hunter-gatherers and the neighboring Ngandu farmers were observed and compared. Twenty Aka and 21 Ngandu 3- to 4-month-olds and 20 Aka and 20 Ngandu 9- to 10-month-olds were observed for 3 hr on each of 4 days so that all 12 daylight hr were covered. The Aka infants were more likely to be held, fed, and asleep or drowsy, whereas Ngandu infants were more likely to be alone and to fuss or cry, smile, vocalize, or play. The amount of crying, soothing, feeding, and sleeping declined over time in both groups. Distal social interaction increased over time among the Ngandu but not among the Aka. Despite striking cultural differences on many variables, however, functional context systematically affected the relative prominence of the infants' behavior in both cultural groups.

Africa↗
PubMed1996

Relation of chemical structure to spatial distribution of sensory responses in rat olfactory epithelium.

1. Electroolfactogram (EOG) recordings were made in three configurations from the rat olfactory epithelium. Each configuration compared recordings in the dorsomedial recess of the epithelium with recordings in ventral or lateral parts of the epithelium. Most comparisons were made with simultaneous recordings. The exception was a series in which the dorsal recess and lateral space between the base of two turbinate bones were directly exposed for odor application and recording. The spatial distributions of maximal responses were largely independent of recording configuration. 2. Simultaneous recordings compared dorsomedial and lateral sites in the epithelium during stimulation with a series of 50 odorants. The odorants that evoked larger responses in the lateral sites were usually compounds that lacked oxygen containing functional groups (such as the carbonyl group). This was true for straight chain and cyclic alkanes, for terpine compounds, and for aromatic compounds. The major exception was cineole, a bicyclic compound. All compounds containing ketone groups evoked larger dorsomedial responses. The responses of aldehydes and esters depended upon whether they were attached to aliphatic or aromatic chains. 3. In the three types of preparation, the sites responding best to ketones were in the same expression zone of the epithelium according to published maps for the rat and mouse. The sites responding best to odors without functional groups were in the far lateral or ventral region and corresponded to one of the two most lateral and ventral expression zones. This fact suggests that the receptors in these regions have a preference for particular chemical properties. This level of analysis cannot determine whether all receptors in each zone have a stronger response to certain properties of these odorants or whether each zone contains different proportions of receptors with these properties.

Anesthesia, Inhalation↗
PubMed1995

Whole body arginine metabolism and nitric oxide synthesis in newborns with persistent pulmonary hypertension.

Despite the potential relevance of the L-arginine-nitric oxide (NO) pathway in the pathophysiology of pulmonary hypertension, no in vivo studies of the kinetics of arginine and NO have been conducted previously in this population. The terminal guanidino N-atom of L-arginine is the precursor for NO, which is oxidized to the stable inorganic nitrogen oxides, nitrite (NO2-) and nitrate (NO3-). Thus, synthesized NO is detected in serum or urine as NO2- and NO3-. The purpose of this investigation was to compare studies of whole body arginine metabolism twice in nine patients with persistent pulmonary hypertension of the newborn (PPHN), using a primed constant i.v. infusion of L-[guanidino-15N2,5,5(2)H2]arginine and L-[5,5,5(2)H3]leucine, first during acute pulmonary vasoconstriction and again during convalescence, and thereby to characterize quantitative aspects of whole body arginine kinetics and NO production, as estimated from the rate of transfer of the 15N-guanidino-label of arginine to urinary nitrate (15NO3-). Arginine flux rates were 84.1 +/- 8.6 mumol.kg-1 h-1 (mean +/- SEM) during acute pulmonary hypertension and increased to 125 +/- 13.2 (p < 0.05) during convalescence, whereas leucine fluxes were unchanged (168.5 +/- 15 versus 178.8 +/- 10.2 mumol.kg-1 h-1), and comparable to those reported in healthy newborns. During convalescence total urinary nitrate excreted increased by 66% (p < 0.05), urinary 15NO3- increased from 0.29 +/- 0.07 to 0.74 +/- 0.15 mumol.d-1 (p < 0.05), and the rate of plasma arginine conversion to NO increased from 10.3 +/- 2.2 to 45.6 +/- 13 mumol.d-1 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1989

Subclinical laminitis in dairy heifers.

By causing poorer horn quality, subclinical laminitis is considered to be a major predisposing cause of other hoof problems, particularly sole ulcers in newly calved heifers. In this study the hind hooves of 136 female Friesian/Holstein cattle aged between four months and two years were examined to discover at what age the signs of subclinical laminitis appeared. Sole haemorrhages were found in the hoof horn of calves as young as five months. The consistent finding of these lesions in heifers of all ages indicated that subclinical laminitis of varying degree was a common condition during the early growing period of young dairy heifers.

Age Factors↗
PubMed1989

An innovative program of counseling family members and friends of seropositive haemophiliacs.

This paper describes current efforts to construct a set of innovative educational and skill building materials targetted at groups of persons with HIV infection, those at risk for HIV, their families and friends, and health professionals. The ENCOUNTERS family of interactive simulations is designed to provide participants with the necessary communication and behavioral skills to deepen their understanding of HIV, to improve their interaction with others in their interpersonal environment, and to more effectively manage stress generated by HIV concerns The ENCOUNTERS family of simulations are built on the principles of role play, but adds to them principles of simulation gaming. The former technique is strengthened by offering active participation for all group members, increased structure, and the opportunity for participants to take different perspectives on an issue of concern in a supportive small group environment.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Apnea of infancy and subsequent neurologic, cognitive, and behavioral status.

A pilot study investigated the neurologic, cognitive, and behavioral consequences of nonfatal infancy apnea. Fifteen formerly apneic, monitored children were compared with age-similar siblings and with age-sex matched playmates. Significant impairment in gross motor development and mild cognitive deficiencies were observed when those who had had apnea were compared with their siblings but not when contrasted with their playmates. Lack of difference between those who had had apnea and playmates might have been due to a selection bias involving assortive friendships. The frequency and the severity of apneic episodes were associated but neither one showed a clear gradient of risk for poor outcome in the areas under study, indicating the possibility that apnea may have a threshold effect on subsequent development.

Apnea↗
PubMed1982

Variability and habituation of nystagmic responses to hot caloric stimulation of normal subjects. Evidence that this test may be inapplicable to monitoring drug-induced vestibular toxicity.

Experiments were performed on 25 otoneurologically "normal' subjects to evaluate the hot caloric test as a screening test for aminoglycoside vestibular toxicity. Using portable equipment under non-ideal conditions, it was found that there was a large inter-subject variability in nystagmic response and that, instead of a random test-retest variability, a systematic variation in response occurred on repeated caloric stimulation with water at 44 degrees C. A response decline (habituation) evident in both the maximum slow phase velocity and the maximum frequency occurred at second test, although the inter-test interval ranged from 24 to 72 hours. After a 3-month interval with no intervening tests, the mean value of the maximum frequency reverted back to the original level. However, there was still a significant reduction in maximum slow phase velocity at this time. Some individuals had a sustained reduction in both parameters. Hence it is concluded that the hot caloric test, used under the conditions described in this study, is not a suitable serial screening method for aminoglycoside vestibular toxicity. The reproducibility of this test under other conditions, or any other caloric test, should be established in normal subjects before employing it as a serial screen for aminoglycoside vestibular toxicity.

Adult↗