PubMed Health⌕ Search

Biomedical subjects

D Hooper

Publications and source records attributed to D Hooper.

At least 19 recordsLinked to original sources
PubMed2001

Phenomenology of high-energy neutrinos in low-scale quantum-gravity models.

We show that neutrino telescopes, optimized for detecting neutrinos of TeV to PeV energy, can reveal threshold effects associated with TeV-scale gravity. The signature is an increase with energy of the cross section beyond what is predicted by the standard model. The advantage of the method is that the neutrino cross section is measured in an energy region where (i) the models are characteristically distinguishable and (ii) the standard model neutrino cross section can be reliably calculated so that any deviation can be conclusively identified.

Journal Article↗
PubMed2000

The spasmodic peptide defines a new conotoxin superfamily.

We purified and characterized a peptide from the venom of Conus textile that makes normal mice assume the phenotype of a well-known mutant, the spasmodic mouse. This "spasmodic" peptide has 27 amino acids, including two gamma-carboxyglutamate (Gla) residues. A cDNA clone encoding the precursor for the peptide was identified; a gamma-carboxylation recognition signal sequence (gamma-CRS) is present in the -1 --> -20 region of the peptide precursor. Both the gamma-CRS and the position of the Gla residues in the mature toxin are notably different from other Gla-containing conopeptides. The spasmodic peptide has a novel disulfide framework and distinct signal sequence which together define a new P-superfamily of conopeptides. A cDNA encoding another member of the P-superfamily was identified from a different species, Conus gloriamaris.

1-Carboxyglutamic Acid↗
PubMed1999

The T-superfamily of conotoxins.

We report the discovery and initial characterization of the T-superfamily of conotoxins. Eight different T-superfamily peptides from five Conus species were identified; they share a consensus signal sequence, and a conserved arrangement of cysteine residues (- -CC- -CC-). T-superfamily peptides were found expressed in venom ducts of all major feeding types of Conus; the results suggest that the T-superfamily will be a large and diverse group of peptides, widely distributed in the 500 different Conus species. These peptides are likely to be functionally diverse; although the peptides are small (11-17 amino acids), their sequences are strikingly divergent, with different peptides of the superfamily exhibiting varying extents of post-translational modification. Of the three peptides tested for in vivo biological activity, only one was active on mice but all three had effects on fish. The peptides that have been extensively characterized are as follows: p5a, GCCPKQMRCCTL*; tx5a, gammaCCgammaDGW(+)CCT( section sign)AAO; and au5a, FCCPFIRYCCW (where gamma = gamma-carboxyglutamate, W(+) = bromotryptophan, O = hydroxyproline, T( section sign) = glycosylated threonine, and * = COOH-terminal amidation). We also demonstrate that the precursor of tx5a contains a functional gamma-carboxylation recognition signal in the -1 to -20 propeptide region, consistent with the presence of gamma-carboxyglutamate residues in this peptide.

Amino Acid Sequence↗
PubMed1999

Determination of differential activities of soluble and membrane-bound catechol-O-methyltransferase in tissues and erythrocytes.

Catechol-O-methyltransferase (COMT) exists as two isoenzymes, a membrane-bound form (MB-COMT) and a soluble form (S-COMT), with different roles in the metabolism of catecholamines and other catechol compounds. This report documents an HPLC assay for separate estimation of S-COMT and MB-COMT activity and examines activities of the two isoenzymes among different rat tissues and in human and rat erythrocytes. Activities of MB-COMT and S-COMT varied widely among tissues. There were higher activities of S-COMT than MB-COMT in all tissues except the adrenal medulla where MB-COMT was the predominant isoenzyme, consistent with the importance of this tissue and MB-COMT for the O-methylation of catecholamines. MB-COMT and S-COMT in rat and human erythrocytes showed divergent levels and patterns of activity. The assay represents a rapid and accurate method for quantifying MB-COMT and S-COMT in various tissues and examining the relative roles of COMT isoenzymes in the metabolism of catechol compounds in health and disease.

Animals↗
PubMed1999

Speciation of cone snails and interspecific hyperdivergence of their venom peptides. Potential evolutionary significance of introns.

All 500 species of cone snails (Conus) are venomous predators. From a biochemical/genetic perspective, differences among Conus species may be based on the 50-200 different peptides in the venom of each species. Venom is used for prey capture as well as for interactions with predators and competitors. The venom of every species has its own distinct complement of peptides. Some of the interspecific divergence observed in venom peptides can be explained by differential expression of venom peptide superfamilies in different species and of peptide superfamily branching in various Conus lineages into pharmacologic groups with different targeting specificity. However, the striking interspecific divergence of peptide sequences is the dominant factor in the differences observed between venoms. The small venom peptides (typically 10-35 amino acids in length) are processed from larger prepropeptide precursors (ca. 100 amino acids). If interspecific comparisons are made between homologous prepropeptides, the three different regions of a Conus peptide precursor (signal sequence, pro-region, mature peptide) are found to have diverged at remarkably different rates. Analysis of synonymous and nonsynonymous substitution rates for the different segments of a prepropeptide suggests that mutation frequency varies by over an order of magnitude across the segments, with the mature toxin region undergoing the highest rate. The three sections of the prepropeptide which exhibit apparently different mutation rates are separated by introns. This striking segment-specific rate of divergence of Conus prepropeptides suggests a role for introns in evolution: exons separated by introns have the potential to evolve very different mutation rates. Plausible mechanisms that could underlie differing mutational frequency in the different exons of a gene are discussed.

Amino Acid Sequence↗
PubMed1997

Tyrosine hydroxylase assay for detection of low levels of enzyme activity in peripheral tissues.

A nonisotopic assay for tyrosine hydroxylase, with optimized signal-to-noise ratios, enables determination of low levels of enzyme activity in peripheral tissues. DOPA produced by the enzyme is measured using HPLC with electrochemical detection. Increased signal-to-noise ratios are obtained by including in the reaction mixture glycerol for reduction of blank values and dihydropteridine reductase and NADPH for regeneration of the tetrahydropteridine cofactor. With this method, tyrosine hydroxylase activity can be detected in as few as 200 PC12 cells and in peripheral tissues at levels as low as 4.5 fmol/min/mg wet weight. The assay permits activity to be assessed in a variety of peripheral tissues.

Animals↗
PubMed1997

Substantial production of dopamine in the human gastrointestinal tract.

Considerable urinary excretion of dopamine metabolites indicates that large amounts of dopamine are produced in unknown locations of the body. This study assessed the contribution of mesenteric organs (gastrointestinal tract, spleen, and pancreas) to the total body production of dopamine in humans and examined the presence of the rate-limiting enzyme for dopamine synthesis, tyrosine hydroxylase, in gastrointestinal tissues. Blood sampled from an artery and portal and hepatic veins in eight subjects and from arterial and renal venous sites in other subjects was analyzed for plasma concentrations of dopamine and its metabolites. The activity and distribution of tyrosine hydroxylase was also examined in tissue samples from the stomach and duodenum. Higher concentrations of dopamine and its metabolites in portal venous than arterial plasma indicated substantial production of dopamine by mesenteric organs (12.0 nmol/min) amounting to 42-46% of the renal removal of circulating dopamine metabolites. Tissue samples showed immunoreactive tyrosine hydroxylase in nonneuronal cell bodies and detectable levels of tyrosine hydroxylase in nonneuronal cell bodies and detectable levels of tyrosine hydroxylase enzyme activity. The results show that mesenteric organs produce close to half of the dopamine formed in the body, most of which is unlikely to be derived from sympathetic nerves but may reflect production in a novel nonneuronal dopaminergic system.

Aged↗
PubMed1996

Mesenteric organ production, hepatic metabolism, and renal elimination of norepinephrine and its metabolites in humans.

This study used regional differences in plasma concentrations of norepinephrine and its metabolites to examine how production of the transmitter by sympathetic nerves, in particular, those innervating mesenteric organs, is integrated with metabolism by the liver and elimination by the kidneys. Higher concentrations of norepinephrine, its glycol metabolites 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol and their sulfate conjugates in portal venous than arterial plasma indicate substantial production of norepinephrine by mesenteric organs (15.5 nmol/min). Much lower concentrations of norepinephrine and its glycol metabolites in plasma leaving than entering the liver indicate their efficient hepatic removal (20 nmol/min). Higher concentrations of vanillylmandelic acid in the hepatic outflow than inflow indicate that this metabolic end product is produced largely from the norepinephrine and glycol metabolites removed by the liver. Renal elimination of vanillylmandelic acid (18-20 nmol/min), produced mainly by the liver (17 nmol/min), and of 3-methoxy-4-hydroxyphenylglycol sulfate (7-9 nmol/min), produced largely by mesenteric organs (7 nmol/min), compromised 86-91% of the total renal elimination of norepinephrine metabolites. The results show that mesenteric organs produce about one-half of the norepinephrine formed in the body. The liver removes substantial amounts of circulating norepinephrine and its glycol metabolites and converts these compounds to vanillylmandelic acid, which is then eliminated from the body by the kidneys. The sulfate conjugates are also metabolic end products eliminated by the kidneys. However, these metabolites are produced by extrahepatic tissues, in particular, mesenteric organs, which represent a significant source of sulfate-conjugated norepinephrine and 3,4-dihydroxyphenylglycol, and the main source of sulfate-conjugated 3-methoxy-4-hydroxyphenylglycol.

Aged↗
PubMed1995

Production and metabolism of dopamine and norepinephrine in mesenteric organs and liver of swine.

Concentrations of catecholamines and their metabolites in plasma entering and exiting mesenteric organs, liver, and kidneys were examined to assess the regional production and metabolism of catecholamines in anesthetized swine. Higher portal venous than arterial plasma concentrations of norepinephrine and its metabolites, 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG), and of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), indicated substantial production of both catecholamines by mesenteric organs, representing 45-50% of total body production. Most dopamine was not metabolized to norepinephrine, suggesting a large nonnoradrenergic contribution to total body dopamine production. Concentrations of norepinephrine, DHPG, normetanephrine, and MHPG were lower in plasma exiting than entering the liver, whereas concentrations of the end-product of norepinephrine metabolism, vanillylmandelic acid (VMA), were higher in outflowing than inflowing plasma. Over 94% of the VMA removed by the kidneys was produced in the liver, consistent with the hepatic source of this metabolite. Removal of DOPAC and HVA by the liver exceeded removal by the kidneys or production by mesenteric organs, indicating greater hepatic than renal elimination of these metabolites from the body and underestimation of mesenteric organ dopamine production based on summed spillovers of dopamine metabolites from the liver into the systemic circulation.

Animals↗
PubMed1994

The neuronal and extraneuronal origins of plasma 3-methoxy-4-hydroxyphenylglycol in rats.

3-Methoxy-4-hydroxyphenylglycol (MHPG) is formed by the sequential actions of monoamine oxidase (MAO) and catechol-O-methyltransferase on norepinephrine within extraneuronal tissues or by extraneuronal O-methylation of 3,4-dihydroxyphenylglycol (DHPG) produced intraneuronally from norepinephrine. This study examined the contributions of neuronal and extraneuronal norepinephrine metabolism to formation of MHPG in rats. Spillover of MHPG into plasma (605 +/- 28 pmol/kg per min) was higher than spillover of DHPG (463 +/- 15 pmol/kg per min), norepinephrine (165 +/- 9 pmol/kg per min) and normetanephrine (56 +/- 4 pmol/kg per min). Comparison of MHPG spillover with the increment in normetanephrine spillover after MAO inhibition (81 pmol/kg per min) combined with the spillover of MHPG derived from circulating normetanephrine (21 pmol/kg per min) indicated that only 17% of plasma MHPG is derived from the extraneuronal deamination and O-methylation of norepinephrine; the remaining 83% is from DHPG produced by deamination of norepinephrine within neurons. The production of MHPG from infused DHPG indicated that 30% of the MHPG in plasma is produced by O-methylation of DHPG after entry of DHPG into the bloodstream and 53% (83-30) from metabolism of DHPG before its entry into the bloodstream. Metabolism of circulating norepinephrine made a minor (1-3%) contribution to plasma concentrations of DHPG and MHPG, but a much larger (46%) contribution to plasma normetanephrine. The results provide a comprehensive examination of norepinephrine metabolism by O-methylation and deamination pathways. Since MHPG is the principal norepinephrine metabolite excreted in the rat, the findings also show that total body turnover of norepinephrine is dependent mainly on neuronal metabolism of the transmitter; at rest extraneuronal pathways contribute as little as 15% to norepinephrine turnover.

Animals↗
PubMed1992

Hyperoxemia profoundly alters breathing pattern and arouses the fetal sheep.

We have recently shown that hyperoxemia alone or combined with umbilical cord occlusion causes continuous breathing and arousal in the fetal sheep (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990). We have not however analyzed the changes in the pattern of breathing associated with these events. To do this, we measured the changes in breathing pattern, electrocortical activity and behaviour on 29 occasions in 15 fetal sheep in late gestation. Fetuses were studied during rest, and during lung distention (about 30 cm H2O) with 100% nitrogen (control), 17% oxygen, 100% oxygen and umbilical cord occlusion. Lung distention was obtained using a high frequency oscillator (Senko Co) and in some fetuses a stroke volume of 0 to 20 cm H2O was used to keep PaCO2 near-constant. We found that lung distention with nitrogen or 17% oxygen did not alter the pattern of breathing or behaviour. In 12 out of 34 (35%) experiments 100% oxygen induced continuous breathing, PaO2 increasing to about 250 torr. In the remaining 22 experiments, PaO2 increased to about 100 torr only and breathing was not continuous but it became continuous upon cord occlusion; with occlusion there was a further increase in PaO2 to 190 torr. The increased breathing with oxygen and occlusion was associated with an increase in breathing output (integral of EMGdi x f), an increase in inspiratory drive (integral of EMGdi/Ti), and a decrease in inspiratory (Ti) and expiratory (Te) times. In ten experiments PaCO2 was kept near-constant and the magnitude of the changes remained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of various concentrations of O2 and umbilical cord occlusion on fetal breathing and behavior.

To test the hypothesis that continuous fetal breathing could be induced by hyperoxemia alone or by hyperoxemia and umbilical cord occlusion, even in the absence of a rise in arterial PCO2 (PaCO2), we studied 18 chronically instrumented fetal sheep on 34 occasions using our window model (18). After a resting cycle (1 low-voltage followed by 1 high-voltage electrocortical activity epoch), the fetal lung was distended via an endotracheal tube using mean airway pressure of approximately cmH2O. Inspired N2, 17% O2, and 100% O2 were given to the fetus during one cycle each. While 100% O2 was given, the umbilical cord was occluded (balloon cuff).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Emergency cimetidine prophylaxis against acid aspiration.

Preoperative cimetidine (300 mg IV) was given to assess timing and efficacy of prophylactic cimetidine to increase gastric pH in emergency surgical patients. Two-thirds had an initial gastric pH less than or equal to 2.5, with a mean pH of 2.13 +/- 0.60 as a group. Cimetidine administration resulted in a significant increase in mean pH at intubation (3.25 +/- 0.90), with a mean preoperative premedication interval of 59 +/- 20 minutes. However, 20% failed to achieve a gastric pH greater than 2.5 prior to intubation. The mean gastric pH at extubation (5.09 +/- 1.55) was also significantly increased compared to precimetidine and preintubation levels. Prophylactic cimetidine might protect many, but not all, emergency patients from acid-induced aspiration pulmonary injury at intubation or extubation.

Adolescent↗
PubMed1981

Psychological change in neurotic depression: a repertory grid and personal construct theory approach.

Personal construct theory and repertory grid methodology were applied to a study of psychological change experienced by a sample of ten neurotic depressives and their matched controls during short-term hospitalization. All subjects completed a repertory grid and the Zung depression scale on admission to hospital. Depressives were characterized by lower self-esteem, more negative social perception and higher scores on the Zung scale. Both measures were repeated at the time of discharge from hospital. Depressives showed a significant reduction in depressive mood, more positive social perception, and a change in th construing of the self; controls showed no changes. It is argued that the use of a quantitative assessment technique reinforced by a theoretical framework results in a more refined understanding of psychological change.

Adult↗