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Biomedical subjects

A F Drake

Publications and source records attributed to A F Drake.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of Lactobacillus acidophilus on antibiotic-associated gastrointestinal morbidity: a prospective randomized trial.

Oral antibiotic therapy can alter the gastrointestinal microflora and result in troublesome gastrointestinal complaints. Patients who have experience with broad-spectrum antibiotics may be reluctant to start or to comply with antibiotic therapy due to the associated discomfort. In the field of otolaryngology, oral antibiotic therapy is commonplace, and patient intolerance of a particular antibiotic may result in compromise to a less effective choice. Yogurt, which contains Lactobacillus acidophilus, is often recommended by practitioners to help reduce the side effects of oral antibiotic therapy. We wanted to objectively evaluate the effect of orally administered L. acidophilus on the gastrointestinal side effects of oral broad-spectrum antibiotic therapy. Twenty-seven outpatients, 10 years of age or older, with ear, sinus, or throat infections, in whom amoxicillin/clavulanate was felt to be the antibiotic of choice, were randomly assigned to amoxicillin/clavulanate only, or amoxicillin/clavulanate and Lactobacillus treatment groups. Each patient was advised by the nursing staff to consume a well-balanced diet, and a detailed explanation of the medication schedule was given. A questionnaire was given to each patient at the conclusion of therapy. The data were analyzed using Spearman's rank-order correlations. Concomitant therapy of L. acidophilus with amoxicillin/clavulanate was associated with a significant decrease in patient complaints of gastrointestinal side effects and yeast superinfection. Almost all patients (89%) reported resolution of infection during the course of therapy. We believe that use of L. acidophilus is warranted in patients on broad-spectrum antibiotic therapy with gastrointestinal complaints.

Adolescent↗
PubMed1995

Structure-activity relationships and physico-chemical properties of synthetic lipopeptide inhibitors of PKC.

Four synthetic lipopeptides, (K-pm 19,31), (K-pm 19,21,31), (K-pm 19,28,31) and (K-pm 19,21,28,31) with the lysine-palmitoyl (K-pm) residue as a lipophilic moiety, based on the pseudosubstrate sequence 19RFARKGALRQKNV31 (R19-V31), were found to be potent protein kinase C (PKC) inhibitors. However, the lipopeptides (K-pm 19,21,31), (K-pm 19,28,31) and (K-pm 19,21,28,31) were also found to act as protein kinase cAMP-dependent (PKA) inhibitors. Peptide (K-pm 19,31), the least water soluble, is marginally selective towards PKC, unlike the other palmitoyl derivatives studied here. Since the non-palmitoylated analogues (K 19,31), (K-ac 19,31), (K 19,21,31) and (K-ac 19,21,31) were inhibitors of PKC but not of PKA, the palmitoyl moiety must play a role in the specificity of protein kinase inhibition. In vitro, the lipophilic peptides showed greater stability to protease-mediated hydrolysis than the pseudosubstrate peptide depending upon the number of lipophilic (K-pm) residues. CD studies showed that in comparison with the peptide analogues, the remarkable resistance of the pseudosubstrate (R19-V31) to adopt an alpha-helix conformation in TFE, known to be strongly alpha-helix inducing, rules out this structure as the peptide binding conformation to PKC. By contrast, in aqueous media all the peptides show an extended conformation that correlates well with their inhibitory activity. This is in compliance with the crystallographic observation that an extended structure has been observed for the (5-24) PKI peptide inhibitor bound to PKA.

Circular Dichroism↗
PubMed1994

Correlations between biological activities and conformational properties for human, salmon, eel, porcine calcitonins and Elcatonin elucidated by CD spectroscopy.

Calcitonin (CT) inhibits osteoclastic bone resorption and induces calcium uptake from body fluids. A comparative study of the conformational behaviours of therapeutic calcitonins [salmon (s), eel (e), a synthetic eel calcitonin analogue (Elcatonin), porcine (p) and human (h) calcitonins] as a function of solvent polarity and temperature have been performed by circular dichroism spectroscopy. Elements of secondary structure were lacking in H2O but could be observed in 2,2,2-trifluoroethanol and sodium dodecyl sulphate. In particular, similar amounts of alpha-helical content (four alpha-helical turns) were estimated in trifluoroethanol despite the considerable differences in amino acid sequences. The relative ability to form an alpha helix, assessed by trifluoroethanol/H2O titration, was found to be Elcatonin > sCT > pCT > eCT > hCT. In Elcatonin, sCT, pCT and eCT the four alpha-helical turns were promoted almost completely in a single step, between 0 and 35% trifluoroethanol, unlike hCT where helical structure formation has been reported to involve two steps over the whole trifluoroethanol/H2O range [Arvinte, T. & Drake, A. F. (1993) J. Biol. Chem. 268, 6408-6414]. In SDS, which mimics the membrane environment, conformational differences (3-4 helical turns in Elcatonin, sCT, eCT versus one helical turn in pCT, hCT) were observed and correlate well with biological activity (Elcatonin = sCT = eCT > pCT = hCT). Low-temperature studies in a cryogenic solvent mixture showed the formation of high alpha-helix content (similar to that in trifluoroethanol) in Elcatonin, sCT, eCT and pCT, whilst a left-handed extended helix (3(1) helix) was formed in hCT. This is consistent with the hypothesis of 'linear' and 'helical' calcitonin receptors [Nakanuta, H., Orlowski, R. C. & Epand, R. M. (1990) Endocrinology 127, 163-169].

Amino Acid Sequence↗
PubMed1994

The effect of variation of substitution on the solution conformation of heparin: a spectroscopic and molecular modelling study.

The effect of variations in substitution on the conformation of iduronate-containing sequences in heparin and heparan sulphate has been studied using a series of chemically-modified heparins in which substitution with O- and N-sulphate and N-acetyl substituents has been systematically altered. Monosaccharides corresponding to residues in these modified heparins have also been investigated. The conformations of the glycosidic linkages in O- and N-desulphated re-N-acetylated heparin, O-desulphated re-N-sulphated heparin, and 6-O-desulphated re-N-sulphated heparin have been compared with those of N-desulphated re-N-acetylated heparin and of heparin itself, which have been compared with those of N-desulphated re-N-acetylated heparin and of heparin itself, which have previously been reported [B. Mulloy, M.J. Forster, C. Jones, and D.B. Davies, Biochem. J., 293 (1993) 849-858]. The overall conformation of all the polysaccharides is shown to be similar, regardless of substitution pattern. The conformational equilibrium of the pyranose ring of iduronic acid residues in the polysaccharides has been monitored by the use of 13C NMR chemical shift temperature coefficients, and shown to be similar for all the modified heparins with the exception of N-desulphated re-N-acetylated heparin. Circular dichroism spectra of all the polysaccharides are reported, and their variations attributed to differences in the proportions of pyranose ring forms in the iduronate conformational equilibrium.

Carbohydrate Conformation↗
PubMed1994

Effects of odorants and irritants on respiratory behavior.

A technique that combines psychophysical measurements with continuous recording of nasal patency and respiratory behavior was used to study the psychophysical and respiratory responses of 10 subjects to well-controlled stimulation with three compounds differing in relative stimulatory effectiveness for nasal olfactory and trigeminal chemoreceptors. All four concentrations of acetic acid, amyl acetate, and phenethyl alcohol were well above the odor detection threshold. The magnitudes of both the increase in odor strength and nasal irritation and the decreases in tidal volume were greatest for acetic acid and least for phenethyl alcohol. Among the odorants, differences in nasal irritation were greater than those in odor strength, and tidal volume appeared to have a reasonably close and inverse relationship to nasal irritation.

Acetates↗
PubMed1994

Artifacts associated with acoustic rhinometric assessment of infants and young children: a model study.

The present study was undertaken to determine in model studies whether currently available acoustic rhinometry instrumentation might be used to analyze the nasal cavity configuration of infants and children. A simple nasal cavity model was constructed using eight Lucite inserts that were placed between standard nosepieces provided by the manufacturer and a 35-cm-long polyvinyl chloride pipe closed at its distal end. To simulate the nasal valve, the inserts were 12 mm in length and had apertures ranging in diameter from 2 to 9 mm. A series of experiments was conducted to evaluate the accuracy with which the acoustic rhinometer measured the size of each insert aperture and the configuration of the model system distal to that aperture. Transmission losses caused errors in the area measurement of the insert aperture and the tube distal to the insert. When the insert aperture was < 6 mm in diameter (0.28 cm2), the aperture area was overestimated by > 10%, whereas the area of the distal tube was underestimated by > 10%. As a result of response lags, the acoustic rhinometer also failed to provide an accurate indication of insert length. Finally, oscillation artifacts caused estimates of the distal pipe area to fluctuate. These three systematic errors are described, and their potential impact on acoustic rhinometry in children is discussed.

Acoustics↗
PubMed1994

Preliminary data on the effect of pharyngeal flaps on the upper airway in children with velopharyngeal inadequacy.

Seven patients who received pharyngeal flaps for velopharyngeal incompetence (VPI) were studied to assess the effect of the procedure on nasal airway size. The findings suggest that the pharyngeal flap does not significantly decrease the upper airway in all patients. The effect of the flap did not correlate with the type of cleft, and was most pronounced in the inspiratory phase of the breathing cycle. Reasons for this variable effect, assumed to be related to an already impaired nasal airway in most cleft patients, are discussed.

Airway Resistance↗
PubMed1994

Nasal cavity area in term infants determined by acoustic rhinometry.

The present study was undertaken to determine whether a modification to commercially available acoustic rhinometry (AR) instrumentation might allow equipment designed for use in adults to determine accurately the nasal cavity configuration of infants and children. The standard wave tube was replaced with a version having a narrow (0.312-cm2) internal diameter (ID). Before use with neonates, the accuracy of this instrument was evaluated using the nasal cavity of a full-term infant cadaver. Acoustic nasal area curves were compared to area measurements of polyvinylsiloxane nasal casts and direct volume measurements of the specimen. AR correlated well with nasal cast data (r = .88) for total nasal cavity area. The acoustic method underestimated the total area at the nasal valve by only 1.8 mm2 (22.1 mm2 vs. 23.9 mm2) and overestimated choanal area by 10 mm2 (56.9 mm2 vs. 46.9 mm2). In addition, AR measured total nasal volume to within 5.2% of the value obtained by direct measurement. In a cohort of 10 normal, term infants, the mean acoustic value for total nasal valve area was 19.2 +/- 0.05 mm2 and for total nasal volume was 1.76 +/- 0.53 cm3. This, the first report of nasal area and volume information in live infants, suggests that the modified AR device has utility both in airway research and as a nasal patency screening tool in the pediatric population.

Acoustics↗
PubMed1994

Circular dichroism.

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Amino Acid Sequence↗
PubMed1993

Comparative study of human and salmon calcitonin secondary structure in solutions with low dielectric constants.

Molecular conformations of salmon (sCT) and human (hCT) calcitonin in media with different concentrations of methanol/water and trifluoroethanol/water have been investigated by fluorescence, circular dichroism (CD) and infrared spectroscopy techniques. In these media, sCT and hCT adopt an alpha-helical structure comprising up to 40-48% of the amino acids. CD experiments reveal that for both peptides, the ordering of the Cys1-Cys7 disulfide link and the alpha-helix formation can be distinguished. Disulfide bond ordering is similar in both calcitonins. sCT adopts the alpha-helical structure more readily than hCT, as solvent polarity is reduced. In 2,2,2-trifluoroethanol (TFE)/water mixtures the alpha-helix formation for both hCT and sCT is a two-step process. The first alpha-helix formation step occurs at lower TFE concentrations (less than 11 mol% TFE for hCT and 6 mol% TFE for sCT). The second alpha-helix formation step represents 50 and 23% of the whole conformational change for hCT and sCT, respectively. Tyrosine fluorescence measurements correlate with the far ultraviolet CD changes associated with the peptide backbone. hCT is seen to adopt a left-handed, extended conformation in aqueous media below -50 degrees C.

Amino Acid Sequence↗
PubMed1993

The structure and mechanism of formation of human calcitonin fibrils.

Turbidity measurements of the kinetics of human calcitonin (hCT) fibrillation showed a linear dependence of the logarithm of fibrillation time (the time the sample is not fibrillated) and the logarithm of hCT concentration. This ln/ln plot linearity and electron microscope observations of fibrils indicate that the fibrillation process can be explained by the double nucleation mechanism that was proposed for the gelation of sickle cell hemoglobin (Ferrone, F. A., Hofrichter, J., Sunshine, H. R., and Eaton, W. A. (1980) Biophys. J. 32, 361-380). Circular dichroism, fluorescence, and infrared spectroscopy studies of fibrils showed that hCT molecules have alpha-helical and beta-sheet secondary structure components. A model for the structure of hCT molecules in fibrils is proposed.

Calcitonin↗
PubMed1993

Control of the mucosal microcirculation in the upper respiratory tract.

This study was designed to investigate the regulatory mechanisms of the mucosal microvascular network in the upper respiratory tract. Tracheal mucosal circulation was observed using a specially constructed chamber that allowed direct microscopic visualization of mucosal arterioles. Solutions of increasing hypertonicity (500 and 900 mOsm) applied to the tracheal epithelium resulted in increasing dilation of the underlying mucosal arterioles (p < 0.001). N(omega)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), a specific inhibitor of nitric oxide synthesis, added to a hypertonic solution inhibited dilation of mucosal arterioles (p < 0.001). Addition of the substrate for nitric oxide synthesis, L-arginine (0.6 mmol/L) to the hypertonic solution containing L-NAME resulted in dilation of mucosal arterioles once again. These data demonstrate that nitric oxide is a crucial mediator in the response of mucosal arterioles to the hypertonic stimulus presented to the epithelial surface of the trachea. Further elucidation of the control of the mucosal microcirculation in the upper respiratory tract could be implemented in new treatment for pathologic processes of the upper respiratory tract such as mucosal congestion and edema.

Analysis of Variance↗
PubMed1993

Nasal airway size in cleft and noncleft children.

Although the effects of cleft lip and palate on nasal airway size and breathing have been reported for adults, little information is available on children. The present study assessed the effect of age on nasal cross-sectional size and, in particular, whether type of cleft influenced the outcome. The results indicate that, while the cleft nose continues to grow with age, it remains about 30% smaller than the noncleft nose. The airway is smallest in patients with unilateral cleft lip and palate and is largest in those with bilateral clefts. The prevalence of oral breathing is considerably higher in the cleft population in comparison to noncleft.

Adolescent↗