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Biomedical subjects

A H Clayton

Publications and source records attributed to A H Clayton.

At least 19 recordsLinked to original sources
PubMed2000

Oriented circular dichroism of a class A amphipathic helix in aligned phospholipid multilayers.

The effect of lipid phase state on the orientation and conformation of a class A alpha-helical peptide on aligned lipid multilayers was examined using oriented circular dichroism spectroscopy. A comparison of oriented spectra in aligned peptide-lipid multilayers with CD spectra of unaligned peptide lipid vesicle complexes is consistent with a preferential alignment of helices parallel to the membrane surface at temperatures above and below the main acyl-chain melting transition temperature of the phospholipid. Changes are observed in the oriented CD spectra with lipid phase state which are attributed to a subtle conformational change of the peptide on the lipid surface. The results are compared with available experimental data on membrane-active lytic and antimicrobial helical peptides.

Amino Acid Sequence↗
PubMed2000

Site-specific tryptophan dynamics in class A amphipathic helical peptides at a phospholipid bilayer interface.

The amphipathic helix plays a key role in many membrane-associating peptides and proteins. The dynamics of helices on membrane surfaces might be of importance to their function. The fluorescence anisotropy decay of tryptophan is a sensitive indicator of local, segmental, and global dynamics within a peptide or protein. We describe the use of frequency domain dynamic depolarization measurements to determine the site-specific tryptophan dynamics of single tryptophan amphipathic peptides bound to a phospholipid surface. The five 18-residue peptides studied are based on a class A amphipathic peptide that is known to associate at the interface of phospholipid bilayers. The peptides contain a single tryptophan located at positions 2, 3, 7, 12, or 14 in the sequence. Association of the peptides with egg phosphatidylcholine vesicles results in complex behavior of both the tryptophan intensity decay and the anisotropy decay. The anisotropy decays were biphasic and were fitted to an associated model where each lifetime component in the intensity decay is associated with a particular rotational correlation time from the anisotropy decay. In contrast, an unassociated model where all components of the intensity decay share common rotational modes was unable to provide an adequate fit to the data. Two correlation times were resolved from the associated analysis: one whose contribution to the anisotropy decay was dependent on the exposure of the tryptophan to the aqueous phase, and the other whose contribution reflected the position of the tryptophan in the sequence. The results are compared with existing x-ray structural data and molecular dynamics simulations of membrane-incorporated peptides.

Amino Acid Sequence↗
PubMed1999

Helix-helix association of a lipid-bound amphipathic alpha-helix derived from apolipoprotein C-II.

The interaction of a peptide derived from the sequence of apolipoprotein C-II (apoC-II) with a model lipid surface has been investigated by fluorescence spectroscopy. ApoC-II19-39, labeled at the N-terminus with 7-nitrobenz-2-oxa-1,3-diazole (NBD), bound to small unilamellar vesicles of phosphatidylcholine with a dissociation constant of 6 microM. The lipid-bound NBD-labeled peptide exhibited a red-edge excitation shift in its emission maximum and anisotropy, consistent with insertion of the probe into the motionally restricted, polar environment provided by the bilayer interface. The small Stokes shift of the NBD fluorophore permits electronic energy homotransfer between peptides on the lipid surface and results in depolarization of the NBD emission. At high surface densities of lipid-bound peptide, the anisotropy of the NBD probe was 33% lower than in corresponding samples in which electronic energy homotransfer was prevented by the addition of an unlabeled peptide. The efficiency of energy transfer between probes was not consistent with a random distribution of peptides on the lipid surface, indicating instead the self-association of lipid-bound apoC-II19-39. We propose that the role of this sequence in apoC-II is not only to mediate binding of protein to a lipid surface, but also to stabilize the lipoprotein complexes by associating with other amphipathic helices within apoC-II and with other apolipoproteins.

4-Chloro-7-nitrobenzofurazan↗
PubMed1999

The structure and orientation of class-A amphipathic peptides on a phospholipid bilayer surface.

The amphipathic alpha-helix is a recognised structural motif that is shared by membrane-associating proteins and peptides of diverse function. The aim of this paper is to determine the orientation of an alpha-helical amphipathic peptide on the bilayer surface. We use five amphipathic 18-residue peptide analogues of a class A amphipathic peptide that is known to associate with a bilayer surface. Tyrosine and tryptophan are used as spectroscopic probes to sense local environments in the peptide in solution and when bound to the surface of unilamellar phosphatidylcholine vesicles. In a series of peptides, tryptophan is moved progressively along the sequence from the nonpolar face (positions 3, 7, 4) to the polar face of the peptide (positions 2, 12). The local environment of the tryptophan residue at each position is determined using fluorescence spectroscopy employing quantum yield, and the wavelength of the emission maximum as indicators of micropolarity. The exposure of the tryptophan residues at each site is assessed by acrylamide quenching. On association with vesicles, the tryptophan residues at positions 3, 7 and 14 are in nonpolar water-shielded environments, and the tryptophan at position 12 is in an exposed polar environment. The tryptophan at position 2, which is located near the bilayer-water interface, exhibits intermediate behaviour. Analysis of the second-derivative absorption spectrum confirmed that the tyrosine residue at position 7 is in a nonpolar water-shielded environment in the peptide-lipid complex. We conclude that these class A amphipathic peptides lie parallel to the lipid surface and penetrate no deeper than the ester linkages of the phospholipids.

Amino Acid Sequence↗
PubMed1999

Tryptophan rotamer distributions in amphipathic peptides at a lipid surface.

The fluorescence decay of tryptophan is a sensitive indicator of its local environment within a peptide or protein. We describe the use of frequency domain fluorescence spectroscopy to determine the conformational and environmental changes associated with the interaction of single tryptophan amphipathic peptides with a phospholipid surface. The five 18-residue peptides studied are based on a class A amphipathic peptide known to associate with lipid bilayers. The peptides contain a single tryptophan located at positions 2, 3, 7, 12, or 14 in the sequence. In aqueous solution, the peptides are unstructured and a triple-exponential function is required to fit the decay data. Association of the peptides with small unilamellar vesicles composed of egg phosphatidylcholine reduces the complexity of the fluorescence decays to a double exponential function, with a reduced dependence of the preexponential amplitude on peptide sequence. The data are interpreted in terms of a rotamer model in which the modality and relative proportions of the lifetime components are related to the population distribution of tryptophan chi1 rotamers about the Calpha-Cbeta bond. Peptide secondary structure and the disposition of the tryptophan residue relative to the lipid and aqueous phases in the peptide-lipid complex affect the local environment of tryptophan and influence the distribution of side-chain rotamers. The results show that measurement of the temporal decay of tryptophan emission provides a useful adjunct to other biophysical techniques for investigating peptide-lipid and protein-membrane interactions.

Amino Acid Sequence↗
PubMed1998

Spectral properties of fluorescein in solvent-water mixtures: applications as a probe of hydrogen bonding environments in biological systems.

Although fluorescein is a widely used fluorescent probe in the biosciences, the effect of solvent environment on its spectral properties is poorly understood. In this paper we explore the use of fluorescein as a probe of the state of hydrogen bonding in its local environment. This application is based on the observation, originally made by Martin (Chem. Phys. Lett. 35, 105-111, 1975), that the absorption maximum of fluorescein undergoes substantial shifts in organic solvents related to the hydrogen bonding power of the solvents. We have extended this work by studying the spectral properties of the dianion form of the probe in solvent-water mixtures. We show that the magnitude of the shift correlates with the alpha and beta parameters of Kamlet and Taft (J. Am. Chem. Soc. 98, 377-383; 2886-2894, 1976), which provide a scale of the hydrogen bond donor acidities and acceptor basicities, respectively, of the solvents. In solvent-water mixtures, these shifts reflect general effects of the solvents on the hydrogen bonding environment of the fluorescein through water-solvent hydrogen bonding and specific effects due to fluorescein-solvent hydrogen bonding. Indeed, both the absorption and fluorescence properties appear to be dominated by these effects indicating that the spectral shifts of the dianion can be used as an indicator of its hydrogen bonding environment. We discuss the application of fluorescein as a probe of hydrogen bonding in the microenvironment immediately surrounding the fluorophore, and we illustrate the effect with reference to the fluorescein-antifluorescein antibody complex where it appears that antibodies selected during the immune response possess binding sites that are increasingly dehydrated and hydrophobic.

Antibodies↗
PubMed1998

Patient satisfaction with psychiatric treatment of menopausal women in a multidisciplinary women's midlife center.

OBJECTIVE: Menopause may be associated with new onset psychiatric symptoms or may exacerbate or heighten preexisting psychiatric problems in women. We present a model center for midlife women, with a multidisciplinary approach to treating this population, and patients' perceptions of satisfaction with treatment received during referral visits to an outpatient psychiatry clinic. DESIGN: In this study, 59 patients were referred from their primary care provider at the midlife center for evaluation by a faculty psychiatrist in an outpatient setting. A brief telephone interview was administered within 1 year of initial evaluation, using items from the Client Satisfaction Questionnaire-8 (CSQ-8) to assess patient satisfaction with psychiatric services received during the referral visits. Findings were based on responses provided by 50 women who were successfully contacted by telephone for the follow-up assessment. RESULTS: For this sample, the mean total client satisfaction score was 27.8 (s = 5.4) of a possible score of 32, which indicated that most women who were referred for psychiatric services reported a positive experience with the services provided by outpatient psychiatrists and reported being very satisfied with their treatment. CONCLUSIONS: We feel that this model center represents a unique way to identify and treat psychiatric disorders in a patient population that may be at high risk for depression and other psychiatric disorders.

Adult↗
PubMed1997

The Changes in Sexual Functioning Questionnaire (CSFQ): development, reliability, and validity.

The Changes in Sexual Functioning Questionnaire (CSFQ), a structured interview/questionnaire designed to measure illness- and medication-related changes in sexual functioning, is presented with evidence of its validity and reliability. Medical students (n = 122) and psychiatry residents (n = 33) completed the CSFQ on two separate occasions. Residents also completed the Derogatis Interview for Sexual Functioning-Self-Report (DISF-SR), a reliable, validated measure used in research on sexual functioning in patient populations. Concurrent validity was established between the CSFQ and the DISF-SR and test-retest reliability was high. The CSFQ is a reliable and valid measure of sexual functioning, useful in both clinical and research settings.

Adult↗
PubMed1997

Comparison of sexual functioning in clinical and nonclinical populations using the Changes in Sexual Functioning Questionnaire (CSFQ).

The Changes in Sexual Functioning Questionnaire (CSFQ), a structured interview/questionnaire designed to measure illness- and medication-related effects on sexual functioning, is presented with initial evidence of its clinical usefulness in differentiating between those who have sexual dysfunction and those who have no dysfunction. Individuals from clinical and nonclinical samples completed the CSFQ. The sample groups were compared on mean scores on the CSFQ and its subscales. Comparative findings indicate that psychiatric patients diagnosed with a mood disorder have significantly lower sexual functioning when compared with nonpsychiatric outpatients, medical students, and psychiatry residents combined. The CSFQ is a useful measure for assessing medication- or illness-related effects on sexual functioning in a systematic way.

Adult↗
PubMed1995

Onset of menses in two adult patients with Prader-Willi syndrome treated with fluoxetine.

Prader-Willi syndrome (PWS) is characterized by hypotonia at birth, hypogonadism, early childhood obesity, and mental deficiency. Hypogonadotropic hypogonadism is a major characteristic of patients with PWS, and it is speculated to be due to hypothalamic insufficiency. Two adult female patients with PWS and no prior history of menses are presented. Both of these patients were treated with fluoxetine for psychopharmacologic management of obsessive features in the form of food preoccupation and hyperphagia or for compulsive behaviors in the form of severe self-injurious behaviors. The two female patients with PWS who had primary amenorrhea developed vaginal bleeding believed to be menses following at least 6 months of treatment with fluoxetine. Mature hypothalamic function is characterized by pulsatile release of gonadotropin-releasing hormone (GnRH) in a critical range of frequency and amplitude. Central nervous system neurotransmitters may modify GnRH secretion. Fluoxetine specifically inhibits the reuptake of serotonin which may impact the hypothalamic-pituitary-ovarian system in female patients with PWS.

Adult↗
PubMed1995

Antidepressant-induced tardive dyskinesia: review and case report.

We report a case of clomipramine-induced tardive dyskinesia (TD) in the setting of chronic use of dextroamphetamine without prior use of neuroleptics, in which the movements persisted after discontinuation of the clomipramine. Other contributing factors include advanced age, history of alcohol abuse, and concomitant administration of hepatic enzyme inhibitors. Other cases of tricyclic-induced TD have occurred primarily in combination with neuroleptics, have involved antidepressants with antidopaminergic actions, or, as in the present case, have resulted from antidepressants with significant anticholinergic effects (n = 17). Predisposing risk factors and potential mechanisms in the precipitation of dyskinesias are discussed.

Aged↗
PubMed1995

Assessment of paroxetine-induced sexual dysfunction using the Changes in Sexual Functioning Questionnaire.

The Changes in Sexual Functioning Questionnaire (see Appendix) was developed as a brief clinical and research instrument to measure sexual function changes accompanying illness or the administration of medications. In a pilot study of patients with major depression being treated with paroxetine, the instrument was useful in delineating three groups of patients: patients who reported increased libido without sexual dysfunction, patients who developed anorgasmia with possible spontaneous resolution (medication side effect and development of tolerance), and patients with long-term sexual dysfunction unaffected by the medication. Change scores accurately differentiated global elements, changes associated with specific factors of sexual response, and drug-specific side effects. All patients had a therapeutic response to treatment with experiences of sexual functioning that could be categorized into one of the three groups.

Adult↗
PubMed1994

Positron-emission tomography and personality disorders.

This study used positron-emission tomography to examine cerebral metabolic rates of glucose (CMRG) in 17 patients with DSM III-R diagnoses of personality disorder. Within the group of 17 personality disorder patients, there was a significant inverse correlation between a life history of aggressive impulse difficulties and regional CMRG in the frontal cortex of the transaxial plane approximately 40 mm above the canthomeatal line (CML) (r = -.56, p = 0.17). Diagnostic groups included antisocial (n = 6), borderline (n = 6), dependent (n = 2), and narcissistic (n = 3). Regional CMRG in the six antisocial patients and in the six borderline patients was compared to a control group of 43 subjects using an analysis of covariance with age and sex as covariates. In the borderline personality disorder group, there was a significant decrease in frontal cortex metabolism in the transaxial plane approximately 81 mm above the CML and a significant increase in the transaxial plane approximately 53 mm above the CML (F[1,45] = 8.65, p = .005; and F[1,45] = 7.68, p = .008, respectively.

Adult↗
PubMedDate not supplied

Increase in white blood cell count and serum sodium level following the addition of lithium to carbamazepine treatment among three chronically psychotic male patients with disturbed affective states.

Three male chronically psychotic patients (mean age 33.0 +/- S.D. 7.2 years), two with schizoaffective disorder and one with organic affective disorder, received carbamazepine (CBZ) because of affective symptoms (and, in one case, partial complex seizures) refractory to management with antipsychotic drugs. Coincident with CBZ administration (and clinical improvement), hyponatremia developed thought to be due to the antidiuretic effect of this drug. Lithium was added to counteract the antidiuretic effect of CBZ. Further clinical improvement ensured, serum sodium levels became normal, and there was an increase in the white blood cell count in each patient. The clinical implications of our findings are discussed.

Adult↗