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Biomedical subjects

S May

Publications and source records attributed to S May.

At least 55 records · Page 3Linked to original sources
PubMed1999

Acute effect of glucose tablets on desire to smoke.

RATIONALE: Previous research suggests that glucose may reduce desire to smoke during periods of abstinence but a definitive test is needed. OBJECTIVE: The present study aimed to determine whether a single administration of oral glucose would reduce desire to smoke in abstaining smokers. METHODS: Thirty-eight smokers attended the laboratory in the afternoon having not smoked since the previous evening. They rated their desire to smoke immediately before and at 5-min intervals for 20 min after chewing four 3-g glucose tablets (experimental group) or four matched placebo tablets (control group). RESULTS: Ratings of desire to smoke decreased to a greater extent in the experimental than the control group. The effect was apparent after 10 min. There was no difference between the groups in terms of feeling "sick" or "satisfied". CONCLUSION: A single dose of glucose has a relatively rapid and detectable effect on desire to smoke and the effect is not mediated by feeling sick. Glucose tablets may be useful in helping to control desire to smoke during periods of abstinence.

Adult↗
PubMed1999

Molecular theory of lipid-protein interaction and the Lalpha-HII transition.

We present a molecular-level theory for lipid-protein interaction and apply it to the study of lipid-mediated interactions between proteins and the protein-induced transition from the planar bilayer (Lalpha) to the inverse-hexagonal (HII) phase. The proteins are treated as rigid, membrane-spanning, hydrophobic inclusions of different size and shape, e.g., "cylinder-like," "barrel-like," or "vase-like." We assume strong hydrophobic coupling between the protein and its neighbor lipids. This means that, if necessary, the flexible lipid chains surrounding the protein will stretch, compress, and/or tilt to bridge the hydrophobic thickness mismatch between the protein and the unperturbed bilayer. The system free energy is expressed as an integral over local molecular contributions, the latter accounting for interheadgroup repulsion, hydrocarbon-water surface energy, and chain stretching-tilting effects. We show that the molecular interaction constants are intimately related to familiar elastic (continuum) characteristics of the membrane, such as the bending rigidity and spontaneous curvature, as well as to the less familiar tilt modulus. The equilibrium configuration of the membrane is determined by minimizing the free energy functional, subject to boundary conditions dictated by the size, shape, and spatial distribution of inclusions. A similar procedure is used to calculate the free energy and structure of peptide-free and peptide-rich hexagonal phases. Two degrees of freedom are involved in the variational minimization procedure: the local length and local tilt angle of the lipid chains. The inclusion of chain tilt is particularly important for studying noncylindrical (for instance, barrel-like) inclusions and analyzing the structure of the HII lipid phase; e.g., we find that chain tilt relaxation implies strong faceting of the lipid monolayers in the hexagonal phase. Consistent with experiment, we find that only short peptides (large negative mismatch) can induce the Lalpha --> HII transition. At the transition, a peptide-poor Lalpha phase coexists with a peptide-rich HII phase.

Elasticity↗
PubMed1999

A high throughput colorimetric cell proliferation assay for the identification of human cytomegalovirus inhibitors.

A colorimetric assay based on the cleavage of the tetrazolium salt WST-1 has been developed for human cytomegalovirus (HCMV) antiviral susceptibility testing and adapted to a microtiter plate format. Optimal conditions were determined and the standard routine assay was calibrated with a viral input of 0.05-0.10 plaque forming unit (p.f.u.)/cell with a density of 2000 cells/well in a 96-well microtiter plate for an incubation period of 7 days. Ganciclovir (9-(2-hydroxy-1(hydroxymethyl) ethyoxymethyl) guanine; DHPG), and cidofovir ((S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine; HPMPC) were used as positive control test compounds to validate the assay. The effective EC50 concentration values obtained with the two antiviral compounds in the present assay were in good agreement with plaque reduction assay results performed in parallel experiments. This method presents the advantage of being easy and rapid to perform, reliable, reproducible, and convenient for use in a high throughput screening capacity.

Antiviral Agents↗
PubMed1999

Determination of the allergenic activity of birch pollen and apple prick test solutions by measurement of beta-hexosaminidase release from RBL-2H3 cells. Comparison with classical methods in allergen standardization.

BACKGROUND: A murine in vitro model of the allergic type I reaction was set up to determine the biologic activity of extracts without involvement of human beings. It is based on beta-hexosaminidase release from passively sensitized RBL cells after allergen challenge. The intended application of this RBL cell assay in the field of quality control of allergenic extracts requires its comparison with established methods. METHODS: The activity of five standardized birch-pollen prick test solutions was determined in parallel by RBL assay, direct IgE binding, IgE-binding inhibition, major allergen content, histamine-release assay, and skin testing. RESULTS: The RBL cell-release assay corresponded well to other methods if a reagin raised against natural birch-pollen extract was used for passive sensitization. However, in the case of a reagin against recombinant Bet v 1, only a decreased activity was observed, presumably because a reduced number of epitopes were recognized by the monospecific reagin. In contrast to standardized birch-pollen extracts, nonstandardized apple extracts showed poor activity in all assays. CONCLUSIONS: This murine model might be a useful tool in the quality control of allergenic extracts. It combines properties of assays based on standardized antisera and of assays that consider IgE cross-linking properties.

Allergens↗
PubMed1999

Comparative study of the anti-human cytomegalovirus activities and toxicities of a tetrahydrofuran phosphonate analogue of guanosine and cidofovir.

Cidofovir is the first nucleoside monophosphate analogue currently being used for the treatment of human cytomegalovirus (HCMV) retinitis in individuals with AIDS. Unfortunately, the period of therapy with the use of this compound may be limited due to the possible emergence of serious irreversible nephrotoxic effects. New drugs with improved toxicity profiles are needed. The goal of this study was to investigate the anticytomegaloviral properties and drug-induced toxicity of a novel phosphonate analogue, namely, (-)-2-(R)-dihydroxyphosphinoyl-5-(S)-(guanin-9'-yl-methyl) tetrahydrofuran (compound 1), in comparison with those of cidofovir. The inhibitory activities of both compounds on HCMV propagation in vitro were similar against the AD 169 and Towne strains, with 50% inhibitory concentrations ranging from 0.02 to 0.17 microgram/ml for cidofovir and < 0.05 to 0.09 microgram/ml for compound 1. A clinical HCMV isolate that was resistant to ganciclovir and that had a known mutation within the UL54 DNA polymerase gene and a cidofovir-resistant laboratory strain derived from strain AD 169 remained sensitive to compound 1, whereas their susceptibilities to ganciclovir and cidofovir were reduced by 33- and 10-fold, respectively. Both compound 1 and cidofovir exhibited equal potencies in an experimentally induced murine cytomegalovirus (MCMV) infection in mice, with a prevention or prolongation of mean day to death at dosages of 1.0, 3.2, and 10.0 mg/kg of body weight/day. In cytotoxicity experiments, compound 1 was found to be generally more toxic than cidofovir in cell lines Hs68, HFF, and 3T3-L1 (which are permissive for HCMV or MCMV replication) but less toxic than cidofovir in MRC-5 cells (which are permissive for HCMV replication). Drug-induced toxic side effects were noticed for both compounds in rats and guinea pigs in a 5-day repeated-dose study. In guinea pigs, a greater weight loss was noticed with cidofovir than with compound 1 at dosages of 3.0 and 10.0 mg/kg/day. An opposite effect was detected in rats, which were treated with the compounds at relatively high dosages (up to 100 mg/kg/day). Compound 1 and cidofovir were nephrotoxic in both rats and guinea pigs, with the epithelium lining the proximal convoluted tubules in the renal cortex being the primary target site. The incidence and the severity of the lesions were found to be dose dependent. The lesions observed were characterized by cytoplasm degeneration and nuclear modifications such as karyomegaly, the presence of pseudoinclusions, apoptosis, and degenerative changes. In the guinea pig model, a greater incidence and severity of lesions were observed for cidofovir than for compound 1 (P < 0.001) with a drug regimen of 10 mg/kg/day.

Animals↗
PubMed1998

31P magnetic resonance spectroscopy in the frontal lobe of major depressed patients.

Most research with 31P-magnetic resonance spectroscopy (31P-MRS) in affective disorders has been done in the field of bipolar disturbances. Reduced frontal and temporal lobe phosphomonoester (PME) concentrations were measured in the euthymic state, whereas increased values were found in the depressed state. In bipolar-II patients reduced phosphocreatine (PCr) concentrations were reported in the euthymic, depressed, and manic state. The aim of the present study was to explore whether PME and PCr were also altered in the frontal lobe of major depressed, unipolar patients. Therefore, we used 31P-MRS to investigate the relative phospholipid and high-energy phosphate concentrations in the frontal lobe of 14 unipolar patients, mostly medicated, and 8 age-matched controls. We found increased PME and decreased ATP values. Other 31P-MRS parameters were not different in both groups. Phosphomonoester percentages correlated negatively with the degree of depression. Thus, the main alterations found in bipolar depressed patients could also be demonstrated in unipolar depressed patients. The results are discussed with regard to disturbed phospholipid and intracellular high-energy phosphate metabolism in depressed patients.

Adenosine Triphosphate↗
PubMed1998

Structure, stability, and thermodynamics of lamellar DNA-lipid complexes.

We develop a statistical thermodynamic model for the phase evolution of DNA-cationic lipid complexes in aqueous solution, as a function of the ratios of charged to neutral lipid and charged lipid to DNA. The complexes consist of parallel strands of DNA intercalated in the water layers of lamellar stacks of mixed lipid bilayers, as determined by recent synchrotron x-ray measurements. Elastic deformations of the DNA and the lipid bilayers are neglected, but DNA-induced spatial inhomogeneities in the bilayer charge densities are included. The relevant nonlinear Poisson-Boltzmann equation is solved numerically, including self-consistent treatment of the boundary conditions at the polarized membrane surfaces. For a wide range of lipid compositions, the phase evolution is characterized by three regions of lipid to DNA charge ratio, rho: 1) for low rho, the complexes coexist with excess DNA, and the DNA-DNA spacing in the complex, d, is constant; 2) for intermediate rho, including the isoelectric point rho = 1, all of the lipid and DNA in solution is incorporated into the complex, whose inter-DNA distance d increases linearly with rho; and 3) for high rho, the complexes coexist with excess liposomes (whose lipid composition is different from that in the complex), and their spacing d is nearly, but not completely, independent of rho. These results can be understood in terms of a simple charging model that reflects the competition between counterion entropy and inter-DNA (rho < 1) and interbilayer (rho > 1) repulsions. Finally, our approach and conclusions are compared with theoretical work by others, and with relevant experiments.

Biophysical Phenomena↗
PubMed1998

A simplified method of calculating an overall goodness-of-fit test for the Cox proportional hazards model.

Grønnesby and Borgan (1996) propose an overall goodness-of-fit test for the Cox proportional hazards model. The basis of their test is a grouping of subjects by their estimated risk score. We show that the Grønnesby and Borgan test is algebraically identical to one obtained from adding group indicator variables to the model and testing the hypothesis the coefficients of the group indicator variables are zero via the score test. Thus showing that the test can be calculated using existing software. We demonstrate that the table of observed and estimated expected number of events within each group of the risk score is a useful adjunct to the test to help identify potential problems in fit.

Clinical Trials as Topic↗
PubMed1998

Cleansing regimens for continence care.

Soap and water can be harmful when used to cleanse patients with fragile skin. Two alternatives to soap and water were tested with elderly, incontinent patients. Further trials are needed with a larger sample and with different patient populations.

Aged↗
PubMed1997

31P magnetic resonance spectroscopy in the dorsolateral prefrontal cortex of schizophrenics with a volume selective technique--preliminary findings.

Pettegrew et al (Arch Gen Psychiatry 48:563-568, 1991) were the first to determine abnormalities concerning phospholipids and high energy metabolites in the dorsolateral prefrontal cortex of drug-naive schizophrenics with 31P magnetic resonance spectroscopy (MRS). Other investigations could not replicate these findings. We included in our study 13 schizophrenic inpatients and 14 age-matched controls. Whereas Pettegrew et al found increased levels of phosphodiesters and decreased levels of phosphomonoesters we measured decreased levels of phosphodiesters in the schizophrenics as compared to controls. One possible explanation for the contradictory findings of the both trials might be the different localization techniques used.

Adult↗
PubMed1997

DNA-lipid complexes: stability of honeycomb-like and spaghetti-like structures.

A molecular level theory is presented for the thermodynamic stability of two (similar) types of structural complexes formed by (either single strand or supercoiled) DNA and cationic liposomes, both involving a monolayer-coated DNA as the central structural unit. In the "spaghetti" complex the central unit is surrounded by another, oppositely curved, monolayer, thus forming a bilayer mantle. The "honeycomb" complex is a bundle of hexagonally packed DNA-monolayer units. The formation free energy of these complexes, starting from a planar cationic/neutral lipid bilayer and bare DNA, is expressed as a sum of electrostatic, bending, mixing, and (for the honeycomb) chain frustration contributions. The electrostatic free energy is calculated using the Poisson-Boltzmann equation. The bending energy of the mixed lipid layers is treated in the quadratic curvature approximation with composition-dependent bending rigidity and spontaneous curvature. Ideal lipid mixing is assumed within each lipid monolayer. We found that the most stable monolayer-coated DNA units are formed when the charged/neutral lipid composition corresponds (nearly) to charge neutralization; the optimal monolayer radius corresponds to close DNA-monolayer contact. These conclusions are also valid for the honeycomb complex, as the chain frustration energy is found to be negligible. Typically, the stabilization energies for these structures are on the order of 1 k(B)T/A of DNA length, reflecting mainly the balance between the electrostatic and bending energies. The spaghetti complexes are less stable due to the additional bending energy of the external monolayer. A thermodynamic analysis is presented for calculating the equilibrium lipid compositions when the complexes coexist with excess bilayer.

Computer Simulation↗
PubMed1997

[Comparison of expectations and competencies of USA and German nursing students].

This study is concerned with the impact of job expectations and job competence in the development of burnout. In an intercultural and longitudinal comparison expectations of job competence of US and German nursing students are investigated by means of half-standardized interviews at the end of their training. First results indicate that American nursing students regard themselves as better prepared for job reality with respect to job competence and theoretical training than German nursing students. On the other hand, they report distinct deficits of their practical training. These results are discussed against the background of the different training courses in the USA and in Germany. Prognoses for different courses of burnout processes are given which have to be tested in future investigations of the longitudinal study.

Attitude of Health Personnel↗
PubMed1996

Threat and coping appraisal as determinants of compliance with sports injury rehabilitation: an application of Protection Motivation Theory.

The aim of this study was to examine the effects of threat appraisal (perceived susceptibility to re-injury or retarded rehabilitation and perceived severity of injury) and coping appraisal (self-efficacy, treatment efficacy and outcome value), in the framework of Protection Motivation Theory (PMT), on compliance to a sports physiotherapist's prescribed modalities and rest. During extensive developmental work, a Sports Injury Rehabilitation Beliefs Survey was constructed with 19 items to assess the PMT components. Five compliance measures were developed from physiotherapist and patient surveys. Data from 62 subjects (68% female, mean +/- S.D. age 21.7 +/- 2.85 years, and involved in many recreational and competitive activities) were obtained from a single university-based sports injury clinic, in a prospective study. The study revealed that over half the subjects were subsequently non-compliant to some degree. Greater perceptions of both susceptibility to retarded rehabilitation and injury severity, at the first appointment, were related to subsequent non-compliant behaviour. Greater self-efficacy in the ability to perform prescribed rehabilitation modalities, stronger beliefs in the treatment efficacy, and higher value attached to rehabilitation, were all related to compliant behaviour. Compliance to restricted activity (or rest) was only related to greater perceptions of susceptibility. The findings provide some support for PMT in this context and offer a basis for designing sports therapist interventions which focus on threat and coping appraisal.

Adaptation, Psychological↗