Search PubMed⌕ Search

Biomedical subjects

D S Gill

Publications and source records attributed to D S Gill.

At least 37 records · Page 2Linked to original sources
PubMed1998

Emergency drugs in dental practice.

An increase in the life expectancy of medically compromised patients has resulted in greater numbers of these individuals within our ageing population. As dental surgeons are increasingly expected to provide care for such patients, the likelihood of a medical emergency occurring within the dental surgery may increase. This article reviews the more common emergency drugs that a dentist may have to administer in the event of a medical emergency. The indications, mode of action, method of administration and dose of each agent are discussed.

Dental Care for Chronically Ill↗
PubMed1997

Both variant forms of interferon-alpha4 gene (IFNA4a and IFNA4b) are present in the human population.

Alpha interferons (IFN-alpha) are a class of cytokines with various activities that are used as therapeutic agents for treatment of cancer and viral and immune disorder diseases. At least 13 IFN-alpha genes and 1 IFN-alpha pseudogene have been identified, which are clustered on human chromosome 9. Among the known IFN-alpha species, a number of allelic variants have been reported. Two variants of IFN-alpha4 (IFN-alpha4a and IFN-alpha4b) are known, which differ from each other by changes in their coding regions at nucleotide positions 220 and 410 and can be distinguished by selective restriction enzyme analysis. We have developed oligonucleotide primers for specific amplification of IFN-alpha4 gene fragments using the polymerase chain reaction (PCR). Genomic DNA obtained from over 28,000 normal healthy individuals and six human cell lines were used in this study. The resulting PCR products were analyzed by restriction endonuclease digestion and DNA sequencing to identify the presence of variant sequences. The results show that the DNA sequences for both variants of IFN-alpha4 are found in the population in nearly equal proportion. Individuals with either homozygous (e.g., alpha4a/alpha4a or alpha4b/alpha4b) or heterozygous (i.e., alpha4a/alpha4b) IFN-alpha4 genes were detected. Among the cell lines, KG-1, EB-3, and HTB-10 cells contain the genes for IFN-alpha4a only, whereas U-937, Namalwa, and Daudi cells contain the genes for both IFN-alpha4a and IFN-alpha4b.

Antineoplastic Agents↗
PubMed1996

Anterior paralimbic mediation of procaine-induced emotional and psychosensory experiences.

BACKGROUND: Procaine activates limbic structures in animals. In humans, acute intravenous administration of procaine yields emotional and psychosensory experiences and temporal lobe fast activity. We studied procaine's acute effects on cerebral blood flow (CBF) in relationship to clinical responses. METHODS: Cerebral blood flow was assessed by positron emission tomography with oxygen-15-labeled water in 32 healthy volunteers. Data were analyzed with statistical parametric mapping and magnetic resonance imaging-directed regions of interest. RESULTS: Procaine increased global CBF and, to a greater extent, anterior paralimbic CBF. Subjects with intense procaine-induced fear compared with those with euphoria had greater increases in left amygdalar CBF. Absolute and normalized left amygdalar CBF changes tended to correlate positively with fear and negatively with euphoria intensity. Procaine-induced visual hallucinations appeared associated with greater global and occipital CBF increases. Absolute occipital CBF increases appeared to correlate positively with visual hallucination intensity. CONCLUSIONS: Procaine increased anterior paralimbic CBF, and different clinical responses appeared to be associated with different patterns of CBF changes.

Adolescent↗
PubMed1996

Interferon-alpha 8b is the only variant of interferon-alpha 8 identified in a large human population.

Three variants of human interferon (IFN)-alpha 8a gene, that is, IFN-alpha 8b, and IFN-alpha 8c, have been reported previously. They differ from each other by changes in their coding region at nucleotide positions 359-360, 372, and 550. Human genomic DNA obtained from over 28,000 healthy blood donors and from 4 human cell lines was used in the polymerase chain reaction (PCR) designed for specific amplification of the IFN-alpha 8 gene fragments. The resulting PCR product was analyzed by (1) restriction endonuclease digestion, (2) DNA sequencing, and (3) allele-specific secondary PCR amplification. Only one sequence for IFN-alpha 8 was identified, and that was for IFN-alpha 8b. The sequences for IFN-alpha 8a and IFN-alpha 8c were not detected after PCR amplification either in the pooled leukocytes obtained from > 28,000 individuals or in cell lines tested. These data suggest that the naturally occurring variant or allele for IFN-alpha 8 in the population is IFN-alpha 8b. IFN-alpha 8a and IFN-alpha 8c variants were consistently below the level of detection of the assays and, if present at all in the population, are very rare.

Alleles↗
PubMed1996

Identification of interferon-alpha 7, -alpha 14, and -alpha 21 variants in the genome of a large human population.

The genes for type I interferon (IFN), which include 14 IFN-alpha genes, 1 IFN-beta gene, 1 IFN-omega gene, and a number of IFN-omega pseudogenes, are clustered on human chromosome 9. Among IFN-alpha genes, a number of variants have been reported. Three variants of IFN-alpha 7 (IFN-alpha 7a, IFN-alpha 7b, and IFN-alpha 7c) and IFN-alpha 14 (IFN-alpha 14a, IFN-alpha 14b, and IFN-alpha 14c) and two variants of IFN-alpha 21 (IFN-alpha 21a and IFN-alpha 21b) are identified. The variants differ from each other by base changes in the coding region and can be distinguished by selective restriction enzyme analysis and DNA sequencing. We have used polymerase chain reaction (PCR) with IFN species-specific oligonucleotide primers for amplification of IFN-alpha 7, IFN-alpha 14, and IFN-alpha 21 gene sequences. Genomic DNA obtained from over 28,000 normal healthy individuals were collected in six pools for PCR amplification. To identify the presence of variant sequences, the resulting PCR products of specific IFN-alpha genes were analyzed by restriction endonuclease digestion and DNA sequencing, with a limit of detection of minor components to 1% and 10%, respectively. The results show that only one variant form for each of IFN-alpha 7, IFN-alpha 14, and IFN-alpha 21, namely, IFN-alpha 7a, IFN-alpha 14c, and IFN-alpha 21b, is detectable in the genomic DNA of the population examined. Similar results were obtained from the analysis of a human myeloblastoid cell line, KG-1.

Chromosomes, Human, Pair 9↗
PubMed1996

Differential effects of an L-type Ca2+ channel antagonist on activity- and phosphorylation-enhanced release of acetylcholine at the neuromuscular junction of the frog in vitro.

The effects of the selective L-type Ca(2+)-channel antagonist nimodipine on changes in the electrophysiological correlates of acetylcholine release induced by activity in the motor nerve or by inhibition of protein dephosphorylation were studied in the isolated sartorius muscle of the frog. Nimodipine (1 microM) had no effect on basal miniature endplate potential (mEPP) frequency or on the quantal content of the endplate potential (EPP) evoked at 0.33 Hz. Stimulation of the motor nerve at frequencies of 20, 40 and 50 Hz progressively increased the quantal content and at 50 Hz caused an increase in mEPP frequency measured at the end of the train. Nimodipine (1 microM) had no effect on the change in either parameter caused by activity in the motor nerve. The L-channel agonist BAYK 8644 had inconsistent effects, causing at 0.33 Hz an increase in quantal content at 55% of the neuromuscular junctions examined. Application of the phosphatase inhibitor okadaic acid (1 microM) caused an increase in miniature endplate potential and/or current [mEPP(C)] frequency but not in quantal content. The increase in spontaneous frequency was reduced by the Ca(2+)-channel blockers nimodipine (1 microM) and cadmium (75 microM). The amplitude of mEPP(C)s was increased by okadaic acid (1 microM), but neither the decay time constant of miniature endplate currents (mEPC) nor the amplitude of endplate currents evoked by iontophoretic application of carbachol was so altered. The activity of electric eel acetylcholinesterase was unchanged by okadaic acid. The present data do not support the concept that the recruitment of normally silent L-type Ca(2+)-channels contributes to activity-dependent increases in acetylcholine release. The results obtained with okadaic acid suggest that protein phosphorylation and dephosphorylation may regulate the activity of L-type channels and the packaging of acetylcholine.

Acetylcholine↗
PubMed1995

Microcalorimetric characterization of the anion-exchange adsorption of recombinant cytochrome b5 and its surface-charge mutants.

The adsorption of recombinant soluble tryptic fragment of rat cytochrome b5 on the strong anion exchanger Mono Q was studied using isothermal titration calorimetry and differential scanning calorimetry (DSC). Titration calorimetry results obtained at low levels of adsorbed protein show increasingly endothermic (unfavorable) enthalpies of binding with increasing surface coverage, confirming the heterogeneous nature of binding. The enthalpy of adsorption declines toward zero at higher loadings. At low surface coverage, enthalpies increase linearly with temperature, giving rise to a positive value of delta Cp. Enthalpies of adsorption depend strongly on the history of the adsorbent. DSC is used to show that cytochrome b5 is stable in both free and adsorbed states at all temperatures used in the titration calorimetric experiments. Site-directed mutants of recombinant cytochrome b5 carrying single charge-neutralizing substitutions are used to test the contributions of particular residues to the thermodynamics of adsorption. Like those derived from van't Hoff analysis of equilibrium adsorption isotherms and HPLC retention data, calorimetric enthalpies of adsorption are positive, confirming the dominant role of entropic effects in ion-exchange adsorption in this system.

Adsorption↗
PubMed1995

Procaine-induced increases in limbic rCBF correlate positively with increases in occipital and temporal EEG fast activity.

Previous independent EEG and PET studies suggest that administration of intravenous procaine hydrochloride selectively activates limbic brain structures. To further elucidate procaine's effects and explore the relationship between quantitative EEG (qEEG) and regional cerebral blood flow (rCBF), we simultaneously recorded qEEG and sampled rCBF using O-15 water PET in 20 healthy volunteers during single-blind injections of saline (baseline condition) followed by intravenous procaine (1.84 mg/kg). After thorough screening of EEG records, a subgroup of 7 subjects with EEG data relatively free of both muscle and movement artifacts was selected for analysis. Quantitative spectral EEG data from right occipital and temporal leads were then correlated with each subject's PET rCBF values on a pixel by pixel basis, both at baseline and after procaine. The most striking finding was that the increases in occipital and temporal omega activity from baseline to procaine positively correlated with rCBF increases in the amygdala and its efferents (p < .05), in a pattern very similar to the rCBF increases seen after procaine administration. This suggests that omega activity may reflect activation of deeper brain limbic structures. Also, the convergence of EEG and PET data further supports procaine's selective limbic activation.

Adult↗
PubMed1995

Interferon-alpha 2 variants in the human genome.

Variants of human leukocyte interferon alpha 2 (IFN-alpha 2a, alpha 2b, and alpha 2c) differ from each other by changes in their coding regions at nucleotide positions 137 and 170. As a result of these nucleotide variations, the DNA sequences of the three variants can be distinguished by selective restriction enzyme analysis. Human genomic DNA obtained from over 28,000 normal healthy individuals was used as templates in the polymerase chain reaction (PCR) to amplify the human IFN-alpha 2 gene sequence. The resulting PCR products were analyzed with restriction nucleases to identify the specific IFN-alpha 2 variant sequences present in the genomic DNA of the population examined. The results show that IFN-alpha 2b was detected as the predominant species and IFN-alpha 2c as a very minor species (< 0.1%). The IFN-alpha 2a gene was not detected in this population.

Alleles↗
PubMed1994

Presence of a preferred anion-exchange binding site on cytochrome b5: structural and thermodynamic considerations.

A preferred chromatographic contact region for adsorption of recombinant soluble tryptic fragment of rat cytochrome b5 on the hydrophilic anion-exchanger Mono Q has been identified using conservative carboxylate-to-amide mutations of charged residues. Equilibrium adsorption isotherms were measured under conditions of full reversibility by high ionic strength, as confirmed by explicit mass balances performed for each experiment. Although cytochrome b5 displays several clusters of negative charge, mutations in one cluster consistently reduce binding affinity and the stoichiometric displacement parameter Z by much greater factors than do mutations in other areas of the molecule. Adsorption heterogeneity derived by fitting isotherms to the Hill equation is reduced by factors which reduce the overall affinity of adsorption. Van't Hoff analyses gave uniformly positive enthalpies of adsorption, and mutational changes in adsorption enthalpy were relatively independent of the site of mutation. These results suggest that enthalpy does not play a dominant role in either affinity or selectivity of anion-exchange adsorption in this system.

Adsorption↗
PubMed1994

Isothermal titration calorimetric study of the association of hen egg lysozyme and the anti-lysozyme antibody HyHEL-5.

The thermodynamics of association of hen egg lysozyme and the antibody HyHEL-5 was characterized by isothermal titration calorimetry. The structure of this complex has been determined to 2.8-A resolution by Sheriff et al. [Sheriff, S., Silverton, E. W., Padlan, E. A., Cohen, G. H., Smith-Gill, S. J., Finzel, B. C., & Davies, D. R. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8075-8079]. The calorimetric enthalpy of association is negative and declines linearly with temperature in the range 10-37 degrees C (delta Cp = -340 +/- 40 cal mol-1 K-1). Entropic contributions calculated using previously determined values of the affinity of association are negative (unfavorable) in this temperature range. This result is consistent with the loss of mobility upon association of the unusually mobile segments of HEL which form the HyHEL-5 epitope. As the affinity of association is approximately constant in this temperature range, an enthalpy-entropy compensation effect is implied. The hydrophobic and vibrational contributions to delta S and delta Cp are estimated using the method of Sturtevant [Sturtevant, J. M. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 2236-2240]. The experimental value of delta Cp is in rather close agreement with the delta Cp estimated from the polar and nonpolar surface areas buried upon association.

Animals↗
PubMed1994

Electrostatic potentials and electrostatic interaction energies of rat cytochrome b5 and a simulated anion-exchange adsorbent surface.

Electrostatic potentials were determined for the soluble tryptic core of rat cytochrome b5 (using a structure derived from homology modeling) and a simulated anion-exchange surface through application of the linearized finite-difference Poisson-Boltzmann equation with the simulation code UHBD. Objectives of this work included determination of the contributions of the various charged groups on the protein surface to electrostatic interactions with a simulated anion-exchange surface as a function of orientation, separation distance, and ionic strength, as well as examining the potential existence of a preferred contact orientation. Electrostatic interaction free energies for the complex of the model protein and the simulated surface were computed using the electrostatics section of UHBD employing a 110(3) grid. An initial coarse grid spacing of 2.0 A was required to obtain correct boundary conditions. The boundary conditions of the coarse grid were used in subsequent focusing steps until the electrostatic interaction free energies were relatively independent of grid spacing (at approximately 0.5 A). Explicit error analyses were performed to determine the effects of grid spacing and other model assumptions on the electrostatic interaction free energies. The computational results reveal the presence of a preferred interaction orientation; the interaction energy between these two entities, of opposite net charge, is repulsive over a range of orientations. The electrostatic interaction free energies appear to be the summation of multiple fractional interactions between the protein and the anion-exchange surface. The simulation results are compared with those of ion-exchange adsorption experiments with site-directed mutants of the recombinant protein. Comparisons of the results from the computational and experimental studies should lead to a better understanding of electrostatic interactions of proteins and charged surfaces.

Adsorption↗
PubMed1994

Tertiary structure of the heme-binding domain of rat cytochrome b5 based on homology modeling.

The in vitro complexes formed between cytochrome b5 and other proteins (e.g. cytochrome c) have served as a useful means to probe electrostatic contributions to macromolecular recognition. Extensive experimentation has been carried out to test the specificity and stability of these complexes, including site-directed mutagenesis based on the heterologous expression of rat cytochrome b5 in E. coli. Despite this interest, there has not been a determination of the complete structure of cytochrome b5. Here we report coordinates for the complete tertiary structure of the heme-binding domain of rat cytochrome b5 based on homology modeling. Protein Data Bank (PDB) coordinates derived from the crystal structure of the highly homologous bovine cytochrome b5 were used for main chain scaffolding. Secondary structures for the termini missing in the bovine structure were generated using homologous sequences derived from an exhaustive search of the PDB database. The model structure was solvated and further refined using energy minimization techniques. The N-terminal residues of the model appear to be in a beta sheet conformation while the carboxy terminus is in a helical conformation. The rest of the rat model is folded virtually identically to the bovine x-ray crystal structure (r.m.s. deviation 1.28 A), despite six sequence differences between the two cores. This homology-based structure should be useful for structure-function analyses of molecular recognition involving cytochrome b5.

Amino Acid Sequence↗
PubMed1994

High-dose gamma-globulin therapy in the reactive haemophagocytic syndrome.

Reactive haemophagocytic syndrome (RHS) is a disorder characterized by systemic proliferation of non-malignant histiocytes occurring most commonly in patients with pre-existing immunological abnormalities or neoplasms. Patients, particularly those with immunosuppression, often have a rapidly progressive fatal course. Treatment is directed at the underlying disorder. In the absence of identifiable cause, the therapy is less satisfactory. We report here three cases of RHS successfully treated with high-dose gamma-globulin therapy. Two of the three patients were immunocompromised and the third occurred during pregnancy. The improvement occurred within 24-72 h and all patients recovered. High-dose i.v. gamma-globulin therapy may be beneficial in RHS.

Adult↗
PubMed1994

Fluctuating symptomatic cryofibrinogenaemia in a patient with left atrial myxoma.

We report a case of left atrial myxoma associated with a fluctuating level of cryofibrinogen. Her initial symptoms and signs were consistent with primary cryofibrinogenaemia, but a repeat episode occurred without the cryofibrinogen being detectable. A more typically embolic cerebro-vascular accident (CVA) occurred, with the subsequent discovery of the patient's myxoma. The cryofibrinogen was again present but it disappeared with resection of the myxoma. We propose that the degree of activation of the coagulation system around the myxoma fluctuated, causing variable conversion of fibrinogen to fibrin, so that at times partially cross-linked fibrin(ogen) resulted in cryofibrinogen, but at other times frank emboli from more complete clotting occurred.

Adult↗
PubMed1993

Anion-exchange chromatographic behavior of recombinant rat cytochrome b5. Thermodynamic driving forces and temperature dependence of the stoichiometric displacement parameter Z.

The HPLC anion-exchange isocratic retention behavior of the recombinant soluble core of wild type rat cytochrome b5 on Mono Q HR 5/5 was investigated as a function of temperature and sodium chloride concentration at fixed eluent flow-rates. Retention was measured over a range of eluent flow-rates at a specified temperature to determine if true adsorption equilibrium could be approximated by the HPLC method. Apparent Van 't Hoff enthalpies of adsorption obtained from the HPLC retention data were positive, indicating an entropically driven spontaneous adsorption process, and were found to decline with increasing ionic strength. The retention results were interpreted in terms of the stoichiometric displacement model to obtain the apparent number of binding sites in the contact region, Z, as a function of temperature and of protein concentration. Z was found to depend significantly on temperature, even under conditions of nearly complete protein recovery, but did not depend on protein concentration at the low loadings studied.

Animals↗