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Biomedical subjects

A F Drake

Publications and source records attributed to A F Drake.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1993

Cleft nose. Form and function.

Clefts of the lip and palate frequently produce nasal deformities that tend to reduce the size of the nasal airway. Surgical correction of nasal, palatal, and pharyngeal structures may compromise breathing further. A significant number of individuals with cleft noses mouthbreathe to some extent because of the high prevalence of airway compromise.

Abnormalities, Multiple↗
PubMed1992

Conformational analysis of the melanin-concentrating hormone core by circular dichroic spectroscopy. Disulphide bridge and tyrosine contributions.

A detailed circular dichroic (CD) study of the conformational flexibility of the melanin-concentrating hormone core [MCH(5-14)] is reported. Variable pH (2-10) and temperature (-80 degrees to +80 degrees C) in aqueous media reveal that CD contributions from tyrosine, disulphide bridge and the amide backbone can be discriminated. Only below -10 degrees C does a preferred -S-S-conformation (P chirality, dihedral angle phi = 90 +/- 10 degrees) dominate. The amide backbone CD contribution varies over all temperatures (-80 degrees to +80 degrees C) providing evidence for a type-II beta-turn at low temperatures, with the emergence of a type-I beta-turn at higher temperatures. Tyrosine exhibits a special behaviour at pH 7. These conclusions are in broad agreement with published NMR studies. Nevertheless, the MCH(5-14) core is seen to be conformationally flexible in aqueous solution at ambient temperatures. Conformation differences are observed in a non-aqueous environment.

Amino Acid Sequence↗
PubMed1992

Stereochemical studies of chiral H-1 antagonists of histamine: the resolution, chiral analysis, and biological evaluation of four antipodal pairs.

The resolution of the H-1 antihistamines chloropheniramine, dimethindene, carbinoxamine, and mebrophenhydramine is described. The optical purity of antipodal products is investigated by chiral HPLC (use of alpha 1-acid glycoprotein and beta-cyclodextrin columns) and NMR (spectra of beta-cyclodextrin inclusion complexes). Configurational relationships among the group are reviewed and assignments are confirmed and extended by circular dichroism evidence. Affinity constants of antipodal pairs for guinea pig ileum and cerebellum sites, determined by gut bath and binding experiments respectively, are reported together with some in vivo tests in man for central effects. Results are discussed in terms of configurational requirements for activity and variations in antipodal potency ratios within the group.

Animals↗
PubMed1992

Assessing the effects of odorants on nasal airway size and breathing.

A technique was developed to obtain continuous measurements of both respiratory behavior and nasal patency in response to well-controlled odorant stimulation. An automated apparatus similar to that described by Walker et al. (27) was used to present precise concentrations of an odorant. The pressure-flow technique (28) was used to continuously measure nasal airway cross-sectional area, nasal airflow rate, air volume and time characteristics associated with breathing before and during odorant stimulation. Immediately following each odorant presentation, subjects entered their psychophysical responses into a microcomputer via an electronic mouse. Respiratory and psychophysical responses of ten normal subjects to four concentrations of acetic acid during eight odorant trials were recorded; eight clean-air trials were also conducted. At the highest concentration, changes in respiratory behavior were observed as early as 200 ms after stimulus onset in some subjects. Inspiratory volumes during odorant presentation were lower than those seen just before stimulation. The magnitude of this decrease was directly related to the concentration of acetic acid and to the perceived intensity of the odor and degree of nasal irritation.

Airway Resistance↗
PubMed1992

Is nasal airway size a marker for susceptibility toward clefting?

Johnston and Hunter (1989) reported that in monozygotic twins discordant for cleft lip +/- palate, the noncleft twins demonstrated what appeared to be a bimodal distribution of nasal cavity width. Two thirds showed reduced airway size and one third showed normal or slightly greater airway size. They suggested that the two-thirds group may represent reduced size of the medial nasal prominences and the other may represent underdevelopment of the maxillary prominence. We were particularly interested in the findings because the difference in distribution may represent differences in pathogenesis and therefore have etiologic significance. With this in mind we assessed nasal cross-sectional areas in 37 subjects with cleft lip or cleft lip +/- palate using the pressure-flow technique during breathing. A group of 72 noncleft individuals served as controls. As expected, the data revealed that subjects with clefts had a significantly reduced nasal airway (p = .0001). More important, the distribution of nasal airway size in the cleft group was similar to that reported by Johnston and Hunter (1989). This comparability suggests that it may be possible to assign most cleft lip +/- palate patients to a particular group. Since heredity may differ among the two groups (Chung et al., 1986), we may have a simple technique to assess the risk of occurrence for cleft lip +/- palate.

Adolescent↗
PubMed1992

Nasal airway in breathing and speech.

Clefts of the lip and palate frequently produce nasal deformities that tend to reduce the size of the nasal airway. Approximately 70% of the cleft population have nasal airway impairment and about 80% "mouth-breathe" to some extent. Surgical correction of nasal, palatal, and pharyngeal structures may further compromise breathing. Type of cleft appears to affect airway size, with unilateral clefts demonstrating the smallest airway. Although a pharyngeal flap may further decrease airway size, some individuals do not notice a postoperative change because of airway compromise prior to flap placement. Speech is a modified breathing behavior that uses the respiratory system to provide an energy source and involves structures within the respiratory tract to modulate this energy into meaningful sounds. The oral, nasal, and pharyngeal structures that are affected by cleft lip and palate during breathing are often compromised for speech as well. The nasal airway plays an important role in controlling speech pressures when velopharyngeal function is impaired. A "good" nose for breathing is often a "bad" nose for speech under such circumstances.

Adult↗
PubMed1991

Correlations between the conformations elucidated by CD spectroscopy and the antigenic properties of four peptides of the foot-and-mouth disease virus.

The conformational features of four related antigenic peptides (A, B, C and USA) from the foot-and-mouth disease virus (FMDV) (VP1; 141-160 of serotype A, subtype 12), assessed by CD, were found to correlate with the serological properties of these peptides. The CD spectra of the four peptides, obtained under cryogenic and solvent titration conditions, were consistent with three conformational components (a left-handed extended helix, an alpha-helix and a 3(10) helix) for peptides A and C and four components (a beta-turn of type II, an alpha-helix, a gamma-turn and a 3(10) helix) for peptides B and USA. The amino acid substitutions at positions 148 and 153, which distinguish the peptides, are therefore responsible for both their conformational and antigenic differences.

Amino Acid Sequence↗
PubMed1991

Left handed alpha-helix formation by a bacterial peptide.

The alpha-helix is a common element of secondary structure in proteins and peptides. In eukaryotic organisms, which exclusively incorporate L-amino acids into such molecules, stereochemical interactions make such alpha-helices, invariably right-handed. Pseudomonas tolaasii Paine is the causal organism of the economically significant brown blotch disease of the cultivated mushroom Agaricus bisporus (Lange) Imbach. P. Tolaasii proceduces an extracellular lipodepsipeptide toxin, tolaasin, which causes the brown pitted lesions on the mushroom cap. Circular dichroism studies on tolaasin in a membrane-like environment indicate the presence of a left-handed alpha-helix, probably formed by a sequence of 7 D-amino acids in the peptide. P. tolaasii represents the first reported example of an organism which has evolved the ability to biosynthesize a left-handed alpha-helix.

Amino Acid Sequence↗
PubMed1991

Divalent cation-sensitive pores formed by natural and synthetic melittin and by Triton X-100.

Leakage of ions and low-molecular-weight metabolites from Lettre cells is induced by synthetic melittin, as effectively as by melittin isolated from bee venom; in each case leakage is inhibited by Ca2+, Zn2+ or H+. Inhibition of leakage by divalent cations is reversible in that Lettre cells incubated with melittin (or with Triton X-100) in the presence of inhibitory amounts of Zn2+, when freed of Zn2+ by EGTA or by centrifugation, begin to leak (in Zn2(+)-sensitive manner). Electrorotation of Lettre cells is altered by melittin, compatible with membrane permeabilization; melittin plus Zn2+ does not alter electrorotation until Zn2+ (and unbound melittin) are removed. Melittin or Triton X-100 added to calcein-loaded liposomes induces leakage of calcein; divalent cations inhibit. Energy transfer between liposome-associated melittin and 2-, 7- or 12-(9-anthroyloxy)stearate (AS) is maximal with 12-AS; addition of Zn2+ has little effect. Circular dichroism spectra of melittin plus liposomes are unaffected by Zn2+. These results show that the formation of divalent cation-sensitive pores is not dependent on the presence of endogenous membrane proteins and that the action of divalent cations is not by displacement of melittin (or Triton) from the lipid bilayer.

Animals↗
PubMed1991

The prevention of postoperative stridor and laryngospasm with topical lidocaine.

Tonsillectomy and adenoidectomy can predispose to stridor and laryngospasm in the immediate postextubation period. A prospectively randomized study of 133 patients undergoing tonsillectomy and adenoidectomy was undertaken to determine if the topical application of 4 mg/kg of 4% lidocaine at the time of intubation would decrease the incidence of postoperative stridor and laryngospasm. Taken together, eight (12%) of 67 control patients suffered stridor or laryngospasm vs two (3%) of 66 patients receiving lidocaine. It is concluded that lidocaine administered topically at the time of intubation for adenotonsillectomy helps prevent postoperative stridor and laryngospasm. Surgery of the upper aerodigestive tract often involves not only the technical aspects of the surgical procedure but also concomitant management of the airway. This can present a challenge to even the most adept otolaryngologist and anesthesiologist. Accidental extubation is always possible, and reintubation can be difficult in the presence of blood and saliva. The difficulty is often compounded with a patient who is not completely paralyzed.

Adenoidectomy↗
PubMed1991

A CD strategy for the study of polypeptide folding/unfolding. A synthetic foot-and-mouth disease virus immunogenic peptide.

The circular dichroism spectrum of the 20-residue immunogenic peptide from the foot-and-mouth disease virus (VP1; 141-160 of serotype A, subtype 12) was solvent- and temperature-dependent. Careful solvent titration revealed two isodichroic points and plateaux consistent with stepwise unfolding of specific stable conformations. Variable temperature studies in cryogenic solvents and urea perturbation were consistent with the existence of three conformational moieties, the left-handed extended helix, the alpha-helix, and the 3(10) helix. The number of residues in each helix was confirmed by CD spectral simulations. The strategy described here can be used to determine the components of a conformational equilibrium and their statistical weights, to study peptide folding and unfolding and to determine the bioactive conformation(s) of linear peptides. The conclusions were supported by 2D-NMR studies. A new mechanism for the stabilization of left-handed extended helices and destabilization of alpha-helices by urea is proposed. The structure of the peptide as resolved by CD spectroscopy is of particular significance since the conformation of this antigenic sequence in situ has so far not been solved by X-ray crystallography.

Amino Acid Sequence↗