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Biomedical subjects

M D Hall

Publications and source records attributed to M D Hall.

At least 19 recordsLinked to original sources
PubMed1998

Cloning of rat brain interleukin-18 cDNA.

The interleukin-1 (IL-1) family comprises IL-1 alpha and IL-1 beta and an endogenous IL-1 receptor antagonist (IL-1ra). IL-1 has diverse actions in the brain and has been implicated in both acute and chronic neurodegeneration. However, neither IL-1 alpha nor IL-1 beta are neurotoxic per se in vivo, so other IL-1 related ligands may be important in neurodegeneration. The cytokine interleukin-18 (also called interferon gamma inducing factor, IGIF) was first isolated from the liver of mice during toxic shock. It was later proposed as a member of the IL-1 family, based on protein sequence homology with IL-1 beta and IL-1ra, and has tentatively been called IL-1 gamma. We cloned IL-18 from adult rat brain and demonstrated, by RT-PCR, that it is expressed constitutively in cerebellum, hippocampus, hypothalamus, cortex and striatum. Rat brain IL-18 shows close homology to mouse and human IL-18, and to the recently published sequence from the rat adrenal gland. Mouse pro-IL-18 and pro-IL-1 beta are processed by caspase-1. We demonstrate that caspase-1 also cleaves rat IL-18 in vitro and that the caspase inhibitor, zVAD-DCB inhibits this cleavage.

Adrenal Glands↗
PubMed1998

Influence of prosodic boundaries on comprehension of spoken English sentences.

Three experiments investigated the role of prosody in the comprehension of auditory sentences. In Exp. 1 an analysis of three novice talkers and one expert talker verified the production parameters of one type of syntactic ambiguity and showed that pitch cues were more prominent than duration cues. In Exp. 2, 16 listeners used prosodic information to make consistent decisions reliably about phrase boundaries. In Exp. 3, 40 participants listened to sentences in which prosody was inconsistent with later morphosyntactic information, indicated their understanding, and then judged whether a visual target was related to the meaning of the sentence. Inconsistent prosody slowed comprehension and contributed to slower, less accurate judgments of sentence meaning. This suggests that prosodic information contributes to the perception of spoken language and can affect comprehension even when the syntactic structure indicated by prosody is contradicted by subsequent morphosyntactic information.

Adult↗
PubMed1996

Bombesin receptors in the brain.

We have shown that in the central nervous system BN receptors are closely associated with 5-HT systems. On a subpopulation of dorsal raphe neurons, NMB receptors are able to depolarize cells by reducing gK+. In one of the target regions of the dorsal raphe 5-HT neurons, the SCN, we have also shown that neurons are excited by BN-related peptides. In the SCN, the GRP receptors excite neurons by two different mechanisms: closure of gK+ and opening of an unidentified cation conductance. Expression of human BN receptors from the brain in CHO cells or Xenopus oocytes shows a very similar pharmacological profile to that seen in the rat brain slice preparations. In the CHO cell line, following BN receptor activation, a major second-messenger path involves hydrolysis of PIP2 by phospholipases to yield IP3, which releases Ca2+ from intracellular stores. In the oocyte expression system, a similar second messenger pathway is clearly apparent, and Ca2+-sensitive gCl- represents the last phase in a cascade of events. The final phase of the mechanism of action in the artificial systems does not involve gK+, suggesting a different second messenger cascade to that in neurons. However, the involvement of phospholipases and their phospholipid products have not been excluded in neurons.

Amino Acid Sequence↗
PubMed1996

Letting go.

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Brain Neoplasms↗
PubMed1995

The effect of post-operative diet on recovery in the first twelve hours after tonsillectomy and adenoidectomy.

The effect of post-operative diet selection on the recovery rate of 100 children ages 3-17 years undergoing tonsillectomy and adenoidectomy (T & A) was studied. In the first 12 h after T & A children were allowed either a 'restricted' diet of only soft foods and liquids or a 'non-restricted' diet of foods preselected and usually eaten by the child. Parental evaluation of the child's general well being, pain level and nausea were evaluated. The number of episodes of emesis, doses of acetominophen and the list of foods and drinks consumed were also recorded. No significant differences in any aspect of recovery were noted between groups. However, a trend towards decreased nausea and parental perception of a more successful general recovery was noted at 12 h in the 'non-restricted' group. Children in the 'non-restricted' group were able to eat foods more often associated with their regular diet. No child from either group experienced any immediate or delayed complications. Implications for children and their families undergoing T & A are discussed.

Acetaminophen↗
PubMed1995

Within-category discrimination of musical chords: perceptual magnet or anchor?

Recent speech research has begun to evaluate the internal structure of categories. In one such study, Kuhl (1991) found that discrimination was poorer for vowel stimuli that were more representative of the category (prototype, or P, set) than it was for less representative stimuli (nonprototype, or NP, set). This finding was interpreted as indicating that a category prototype may function as a "perceptual magnet", effectively decreasing perceptual distance, and thus discriminability, between stimuli. The present study examines the function of prototypes in a musical category--another natural, but nonspeech category. Paralleling the Kuhl study, representative (P) and less representative (NP) sets of major triad stimuli were constructed, based on equal temperament. Musically experienced subjects rated the stimuli in each set for a goodness as a major triad, with the highest rated stimulus serving as a prototype standard for a subsequent discrimination task. Results from the discrimination task demonstrated better performance in the P context than in the NP context. The current nonspeech results indicate that a prototype functions as an anchor rather than a magnet. In addition to providing a natural, nonspeech standard for comparison with speech findings, the results provide some important insights into the nature of musical categories.

Humans↗
PubMed1994

Crystallization of catechol-1,2 dioxygenase from Pseudomonas arvilla C-1.

The metalloenzyme catechol 1,2-dioxygenase from Pseudomonas arvilla C-1 consists of three isozymes formed by combinations of two non-identical subunits; alpha alpha, alpha beta and beta beta; with molecular masses of 59,000, 63,000 and 67,000 Da, respectively. The alpha alpha isozyme crystallizes in the orthorhombic space group C222(1) with unit cell dimensions a = 62.7 A, b = 71.5 A, c = 187.1 A. The rectangular plates diffract to 2.6 A resolution. This is the first dioxygenase to be crystallized that uses catechol as a substrate. Comparison of the structure of this enzyme with protocatechuate 3,4-dioxygenase will provide basic information about the mechanisms of subunit association, substrate selectivity, and the origins of metabolic diversity in enzymes.

Catechol 1,2-Dioxygenase↗
PubMed1993

Crystal structure of a ternary complex of Escherichia coli malate dehydrogenase citrate and NAD at 1.9 A resolution.

The structure of malate dehydrogenase from Escherichia coli complexed with the substrate analog, citrate and the cofactor NAD, has been determined by X-ray crystallography. A monoclinic crystal of the malate dehydrogenase, grown in citrate buffer, was soaked in 10 mM NAD solution and found to be isomorphous with the apo-form. The X-ray data extended to 1.9 A, nearly the same resolution limit as the apo-enzyme crystals. The ternary complex of malate dehydrogenase has very few conformational differences from that of the pseudo binary complex of enzyme with bound citrate. In addition, the NAD molecule has a very similar conformation to the NAD as found in the crystal structure of the cytosolic eukaryotic malate dehydrogenase. Similar hydrogen bond interactions are made by both enzymes from polar groups belonging to the NAD. Such interactions include hydrogen bonds from the ribose oxygens and the phosphate oxygens, to backbone amide and carbonyl atoms of the protein and to side-chains of a select few conserved hydrophilic residues. The only notable difference occurs in the active site region where the nicotinamide moiety is obstructed from further entering the active site by the C-6 carbonyl atoms of citrate. In this position there are no direct polar interactions between the protein and the nicotinamide moiety. Energy minimization of the structure with malate substituted for citrate in the active site shows that the nicotinamide moiety assumes the same position in the active site as the NAD in cytosolic malate dehydrogenase. The carboxamide atoms of the energy minimized model make significant hydrogen bond interactions with the catalytic residue, H177, and with the main-chain atoms of I117 and V146 in the vicinity of the active site, while the position of the rest of the cofactor remains unchanged.

Binding Sites↗
PubMed1992

Crystal structure of Escherichia coli malate dehydrogenase. A complex of the apoenzyme and citrate at 1.87 A resolution.

The crystal structure of malate dehydrogenase from Escherichia coli has been determined with a resulting R-factor of 0.187 for X-ray data from 8.0 to 1.87 A. Molecular replacement, using the partially refined structure of porcine mitochondrial malate dehydrogenase as a probe, provided initial phases. The structure of this prokaryotic enzyme is closely homologous with the mitochondrial enzyme but somewhat less similar to cytosolic malate dehydrogenase from eukaryotes. However, all three enzymes are dimeric and form the subunit-subunit interface through similar surface regions. A citrate ion, found in the active site, helps define the residues involved in substrate binding and catalysis. Two arginine residues, R81 and R153, interacting with the citrate are believed to confer substrate specificity. The hydroxyl of the citrate is hydrogen-bonded to a histidine, H177, and similar interactions could be assigned to a bound malate or oxaloacetate. Histidine 177 is also hydrogen-bonded to an aspartate, D150, to form a classic His.Asp pair. Studies of the active site cavity indicate that the bound citrate would occupy part of the site needed for the coenzyme. In a model building study, the cofactor, NAD, was placed into the coenzyme site which exists when the citrate was converted to malate and crystallographic water molecules removed. This hypothetical model of a ternary complex was energy minimized for comparison with the structure of the binary complex of porcine cytosolic malate dehydrogenase. Many residues involved in cofactor binding in the minimized E. coli malate dehydrogenase structure are homologous to coenzyme binding residues in cytosolic malate dehydrogenase. In the energy minimized structure of the ternary complex, the C-4 atom of NAD is in van der Waals' contact with the C-3 atom of the malate. A catalytic cycle involves hydride transfer between these two atoms.

Amino Acid Sequence↗
PubMed1992

Musical duplex perception: perception of figurally good chords with subliminal distinguishing tones.

In a variant of duplex perception with speech, phoneme perception is maintained when distinguishing components are presented below intensities required for separate detection, forming the basis for the claim that a phonetic module takes precedence over nonspeech processing. This finding is replicated with music chords (C major and minor) created by mixing a piano fifth with a sinusoidal distinguishing tone (E or E flat). Individual threshold intensities for detecting E or E flat in the context of the fixed piano tones are established. Chord discrimination thresholds defined by distinguishing tone intensity were determined. Experiment 2 verified masked detection thresholds and subliminal chord identification for experienced musicians. Accurate chord perception was maintained at distinguishing tone intensities nearly 20 dB below the threshold for separate detection. Speech and music findings are argued to demonstrate general perceptual principles.

Adult↗
PubMed1991

Purification and crystallization of recombinant Escherichia coli malate dehydrogenase.

Malate dehydrogenase from Escherichia coli has been crystallized with polyethylene glycol and citrate buffer at pH 5.7. The enzyme was obtained from an E. coli strain in which the chromosomal malate dehydrogenase gene was contained on a pBR322 vector. Two types of crystals have been observed; a monoclinic C2 form and an orthorhombic C222(1) form, which is found infrequently. Monoclinic crystals were used as seeds in several rounds of crystallization until large crystals suitable for diffraction analysis were available. A complete X-ray data set to 2.0 A has been collected.

Chromatography, Ion Exchange↗
PubMed1991

Molecular cloning and primary structure of squid (Loligo forbesi) rhodopsin, a phospholipase C-directed G-protein-linked receptor.

The sequence of squid (Loligo forbesi) rhodopsin was determined by protein and cDNA sequencing. The protein has close similarity to octopus rhodopsin, having an N-terminal region (residues 1-340) which resembles other guanine-nucleotide-binding protein (G-protein)-linked receptors and a repetitive proline-rich C-terminus (residues 340-452). Comparison of the sequence of squid rhodopsin with those of other members of the G-protein-linked receptor superfamily reveals features which we predict to have both structural and functional importance.

Amino Acid Sequence↗
PubMed1991

Elective resection of 332 abdominal aortic aneurysms in a southern West Virginia community during a recent five-year period.

This study analyzed 33 variables that might potentially affect outcome in a series of 332 consecutive elective abdominal aortic aneurysm repairs in a southern West Virginia community. One of the interesting features of this series was that the repairs were done by 22 surgeons with varying degrees of experience. The mortality and complication rates were compared for various potential risk factors by both univariant methods (chi 2, Fisher's exact, and Student t tests) and multivariant methods of analysis. Our early mortality (2.1%) and postoperative complication rates were consistent with those of other series. With multiple linear regression models, five factors were selected as significant independent risk factors associated with an increasing number of postoperative complications: the number of blood transfusions (p less than 0.0001), left renal vein ligation (p less than 0.0001), the presence of greater than 50% renal artery stenosis (p = 0.0012), the lesser experience of the surgeon (p = 0.0203), and the history of prior cardiac catheterization (p = 0.0245). The only factor statistically correlated with mortality rate was an increased number of postoperative complications (p less than 0.0001). Neither postoperative complications nor mortality rate was found to be significant and independently influenced by other demographic, clinical, or operative factors. It is tempting to speculate that surgeons with less experience might be well served to refer patients with significant renal artery stenosis and coronary artery disease. Our mortality and complication rates were not increased by performing preoperative angiography and therefore prudent surgeons may find this helpful in selecting patients for safer repair.

Aged↗
PubMed1990

The way it is.

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Female↗
PubMed1989

Modulation of hypothalamic cholecystokinin receptor density with changes in magnocellular activity: a quantitative autoradiographic study.

A combination of autoradiographical techniques and computerized image analysis has been used to study the distribution and density of cholecystokinin receptors in the paraventricular and supraoptic nuclei of animals in which the magnocellular-posterior pituitary axis is activated, namely, in salt-loaded (2% sodium chloride) and homozygous Brattleboro rats. [125I]cholecystokinin octapeptide binding was greatly elevated in the paraventricular, supraoptic and accessory nuclei of salt-loaded and homozygous Brattleboro rats, compared to the respective control animals. Furthermore, under these conditions [125I]cholecystokinin octapeptide binding in the paraventricular nucleus was localized almost exclusively to magnocellular subdivisions, and especially to those containing predominantly oxytocin neurons. Autoradiographical competition studies revealed that the increase in [125I]cholecystokinin octapeptide binding in magnocellular nuclei reflected an increase in receptor number (Bmax) rather than affinity (Kd). These results suggest that cholecystokinin receptor density in the paraventricular, supraoptic and accessory magnocellular nuclei is closely linked to magnocellular neurosecretory activity and raises the possibility that cholecystokinin receptors may be involved in oxytocin and vasopressin release processes.

Animals↗